WorldWideScience

Sample records for amphetamines

  1. Amphetamines

    Science.gov (United States)

    ... site Sitio para adolescentes Body Mind Sexual Health Food & Fitness Diseases & ... español Anfetaminas What It Is: Amphetamines are very addictive stimulants. They speed up functions in the brain and ...

  2. Amphetamine derivative related deaths.

    Science.gov (United States)

    Lora-Tamayo, C; Tena, T; Rodríguez, A

    1997-02-28

    Amphetamine its methylendioxy (methylendioxyamphetamine methylenedioxymethylamphetamine, methylenedioxyethylamphetamine) and methoxy derivatives (p-methoxyamphetamine and p-methoxymethylamphetamine) are widely abused in Spanish society. We present here the results of a systematic study of all cases of deaths brought to the attention of the Madrid department of the Instituto Nacional de Toxicologia from 1993 to 1995 in which some of these drugs have been found in the cadaveric blood. The cases were divided into three categories: amphetamine and derivatives, amphetamines and alcohol, amphetamines and other drugs. Data on age, sex, clinical symptoms, morphological findings, circumstances of death, when known, and concentration of amphetamine derivatives, alcohol and other drugs in blood are given for each group. The information provided here may prove to be useful for the forensic interpretation of deaths which are directly or indirectly related to abuse of amphetamine derivatives.

  3. Substance use - amphetamines

    Science.gov (United States)

    ... a test. Others use them to boost their performance in sports. Amphetamines also cause the brain to release dopamine. ... or violent behavior Restlessness and tremors Skin sores Sleep problems Tooth decay (meth mouth) People who use ...

  4. Treatment for amphetamine withdrawal.

    Science.gov (United States)

    Shoptaw, Steven J; Kao, Uyen; Heinzerling, Keith; Ling, Walter

    2009-04-15

    Few studies examined treatments for amphetamine withdrawal, although it is a common problem among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse to amphetamine use. In clinical practice, medications for cocaine withdrawal are commonly used to manage amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two illicit substances are different. To assess the effectiveness of pharmacological alone or in combination with psychosocial treatment for amphetamine withdrawals on discontinuation rates, global state, withdrawal symptoms, craving, and other outcomes. MEDLINE (1966 - 2008), CINAHL (1982 - 2008), PsycINFO (1806 - 2008), CENTRAL (Cochrane Library 2008 issue 2), references of obtained articles. All randomised controlled and clinical trials evaluating pharmacological and or psychosocial treatments (alone or combined) for people with amphetamine withdrawal symptoms. Two authors evaluated and extracted data independently. The data were extracted from intention-to-treat analyses. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess dichotomous outcomes. The Weighted Mean Difference (WMD) with 95% CI was used to assess continuous outcomes. Four randomised controlled trials (involving 125 participants) met the inclusion criteria for the review. Two studies found that amineptine significantly reduced discontinuation rates and improved overall clinical presentation, but did not reduce withdrawal symptoms or craving compared to placebo. The benefits of mirtazapine over placebo for reducing amphetamine withdrawal symptoms were not as clear. One study suggested that mirtazapine may reduce hyperarousal and anxiety symptoms associated with amphetamine withdrawal. A more recent study failed to find any benefit of mirtazapine over placebo on retention or on amphetamine withdrawal symptoms. No medication is effective for treatment of amphetamine

  5. Detection of amphetamine following administration of fenproporex.

    Science.gov (United States)

    Cody, J T; Valtier, S

    1996-10-01

    Drugs that are metabolized to amphetamine or methamphetamine are potentially significant concerns in the interpretation of amphetamine-positive drug testing results. A number of different compounds have been reported to produce amphetamine in the urine of users. One of these compounds, fenproporex, has been shown to produce amphetamine. Previous reports indicate that the parent compound can be detected only for a few hours following administration, whereas the amphetamine can be detected for several days. Administration of fenproporex to five healthy volunteers resulted in amphetamine being detected in the urine of all subjects. Peak concentrations of amphetamine were detected at approximately 6-20 h postdose and ranged from approximately 1200 to 2100 ng/mL amphetamine. Amphetamine could be detected (> 5 ng/mL) in the urine for up to 119 h. Analysis of the metabolically produced amphetamine showed the presence of both enantiomers, which can be helpful in the differentiation of some illicit amphetamine use from the use of this precursor drug. More significantly, all samples that contained amphetamine at a concentration of at least 500 ng/mL were shown to also contain measurable amounts of the parent compound.

  6. Metabolic Precursors to Amphetamine and Methamphetamine.

    Science.gov (United States)

    Cody, J D

    1993-12-01

    Analysis and interpretation of amphetamine results is a challenging process made difficult by a number of factors. One of the complications comes from determination of the origin of amphetamine or methamphetamine in a sample. Given the relatively rare occasions that either of these two drugs are prescribed, legal prescription of one of these drugs is seldom a reason for positive findings. A number of other precursor compounds are metabolized by the body to amphetamine or methamphetamine, many of which could be used for legitimate reasons. Fourteen different metabolic precursors of amphetamine or methamphetamine are included in this review. They are amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Medical use, metabolism, analysis, and interpretation are described to afford sufficient information to evaluate the possible involvement of these drugs in positive amphetamine or methamphetamine results. Copyright © 1993 Central Police University.

  7. Amphetamine

    Science.gov (United States)

    ... one else can take it accidentally or on purpose. Keep track of how many tablets or how ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  8. Effect of amphetamine on human macronutrient intake.

    Science.gov (United States)

    Foltin, R W; Kelly, T H; Fischman, M W

    1995-11-01

    Six male subjects participated in a 15-day residential study examining the effects of amphetamine on macronutrient intake. During the first 11 days, carbohydrate intake was manipulated by providing lunch meals high (155 g) or low (25 g) in carbohydrate. Subjects received oral d-amphetamine (5, 10 mg/70 kg, BID) or placebo. Total daily caloric intake was similar under both lunch conditions (approximately 3400/Kcal), but carbohydrate contributed more energy under the high-carbohydrate condition. Both doses of amphetamine decreased total caloric intake to approximately 2600 Kcal, by decreasing the number of eating bouts, without affecting macronutrient selection. During the last four days subjects received a higher daily dose of amphetamine (30 mg/70 kg in four doses) or placebo, and were allowed to self-select lunch. Although 30 mg amphetamine decreased intake of all macronutrients, the relative contribution of carbohydrate to total caloric intake was increased from 54% to 62%, while the contribution of fat was decreased from 32% to 26% and the contribution of protein was decreased from 14% to 12%. Thus, at a high dose, amphetamine altered the relative contribution of specific macronutrients to total caloric intake.

  9. Clobenzorex: evidence for amphetamine-like behavioral actions.

    Science.gov (United States)

    Young, R; Darmani, N A; Elder, E L; Dumas, D; Glennon, R A

    1997-02-01

    Clobenzorex, an optically active N-substituted derivative of (+)amphetamine, has been identified on the illicit market. Because so little is known regarding the pharmacology or abuse potential of this agent, it was examined in tests of stimulus generalization in rats trained to discriminate 1 mg/kg of (+)amphetamine from vehicle to determine if it would produce amphetamine-appropriate responding. Clobenzorex (ED50 = 6.6 mg/kg) substituted for (+)amphetamine (ED50 = 0.3 mg/kg) but was approximately twenty times less potent than the training drug. Clobenzorex was also compared with (+)amphetamine and cocaine for its ability to induce locomotor stimulation and rearing frequency in mice. Clobenzorex was active in both assays but was less potent than either (+)amphetamine or cocaine. It is concluded that, although weaker than (+)amphetamine, clobenzorex constitutes an agent with amphetamine-like central stimulant behavioral properties.

  10. The fast and furious : Cocaine, amphetamines and harm reduction

    NARCIS (Netherlands)

    J-P.C. Grund (Jean-Paul); P. Coffin (Philip); M. Jauffret-Roustide (Marie); M. Dijkstra (Minke); D. de Bruin (Dick); P. Blanken (Peter)

    2010-01-01

    textabstractCocaine and amphetamines (‘stimulants’) are distinct central nervous system stimulants with similar effects (Pleuvry, 2009; Holman, 1994). Cocaine is a crystalline tropane alkaloid extracted from coca leaves. Amphetamines are a subclass of phenylethylamines with primarily stimulant

  11. Metabolic production of amphetamine following administration of clobenzorex.

    Science.gov (United States)

    Valtier, S; Cody, J T

    1999-01-01

    Many of the anorectic drugs that are metabolized to amphetamine and/or methamphetamine pose significant concerns in the interpretation of amphetamine-positive drug testing results. One of these drugs--clobenzorex--has been shown to produce amphetamine. Thirty milligrams of clobenzorex hydrochloride, in the form of a single Asenlix capsule (Roussel, Mexico), were administered orally to five human volunteers with no history of amphetamine, methamphetamine or clobenzorex use. Following administration, urine samples (total void volume) were collected ad lib for seven days and pH, specific gravity and creatinine values were determined. To determine the excretion profile of amphetamine and parent drug, samples were extracted, derivatized, and analyzed by gas chromatography/mass spectrometry (GC/MS) using a standard amphetamine procedure with additional monitoring of ions at m/z 91, 118, 125 and 364 for the detection of clobenzorex. Peak concentrations of amphetamine were detected at 4 to 19 h postdose and ranged from approximately 715 to 2474 ng/mL amphetamine. Amphetamine could be detected (> 5 ng/mL) in the urine in one subject for up to 116 h postdose. GC/MS was also used to determine the enantiomeric composition of the metabolite, amphetamine. This analysis revealed the metabolically derived amphetamine was only the d-enantiomer. This differs from previous literature which indicates clobenzorex is the racemic N-orthochlorobenzyl derivative of amphetamine.

  12. 78 FR 67365 - Determination That Adderall (Amphetamine Aspartate; Amphetamine Sulfate; Dextroamphetamine...

    Science.gov (United States)

    2013-11-12

    ... the Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. 98-417) (the 1984... No. Drug Applicant NDA 011522 ADDERALL Teva Womens Health (amphetamine Inc., 41 Moores aspartate; Rd...

  13. physiological effects of the amphetamines during exercise

    African Journals Online (AJOL)

    PHYSIOLOGICAL EFFECTS OF THE AMPHETAMINES DURING EXERCISE* c. H. WYNDHAM, G. G. ROGERS, A. J. S. BENADE AND N. B. STRYDOM, Human Sciences Laboratory, Chamber of. Mines of SOUTh Africa, Johannesburg. SUMMARY. Oxygen consumption, heart rate, minute ventilation and blood lactate were ...

  14. Amphetamine and fenproporex levels following multidose administration of fenproporex.

    Science.gov (United States)

    Cody, J T; Valtier, S; Stillman, S

    1999-01-01

    Drugs that are metabolized to amphetamine or methamphetamine are potentially of significant concern in the interpretation of positive drug-testing results for amphetamines. A number of different drugs have been reported to produce amphetamine in the urine of users. One of these compounds, fenproporex, has been shown to be metabolized to amphetamine, and previous reports indicated the parent compound could be detected at low levels for up to 48 h. Administration of fenproporex for seven days (one 10-mg dose per day) to five healthy volunteers resulted in amphetamine being detected in the urine of all subjects. Peak concentrations of amphetamine ranged from approximately 2850 to 4150 ng/mL. Amphetamine could be detected (> or = 5 ng/mL) in the urine for up to nearly 170 h after the last dose. Analysis of the metabolically produced amphetamine showed the presence of both enantiomers, which can be helpful in the differentiation of some illicit amphetamine use from the use of this precursor drug. In addition, evaluation of the enantiomeric composition of the metabolite (amphetamine) can be a valuable tool in the interpretation of time since last dose. More significantly, all samples that contained amphetamine at a concentration of > or = 500 ng/mL were shown to also contain detectable amounts of the parent compound.

  15. Raman Optical Activity and Raman Spectra of Amphetamine Species

    DEFF Research Database (Denmark)

    Berg, Rolf W.; Shim, Irene; White, Peter Cyril

    2012-01-01

    Theoretical calculations and preliminary measurements of vibrational Raman optical activity (ROA) spectra of different species of amphetamine (amphetamine and amphetamine-H+) are reported for the first time. The quantum chemical calculations were carried out as hybrid ab initio DFT-molecular orbi......Theoretical calculations and preliminary measurements of vibrational Raman optical activity (ROA) spectra of different species of amphetamine (amphetamine and amphetamine-H+) are reported for the first time. The quantum chemical calculations were carried out as hybrid ab initio DFT...... are employed for identification purposes. The DFT calculations show that the most stable conformations are those allowing for close contact between the aromatic ring and the amine hydrogen atoms. The internal rotational barrier within the same amphetamine enanti- omer has a considerable influence on the Raman...

  16. Cerebral uptake of radioiodinated amphetamines - basic research and clinical results

    International Nuclear Information System (INIS)

    Biersack, H.J.; Kluenenberg, H.; Friedrich, G.; Knopp, R.; Ledda, R.; Doppelfeld, E.; Winkler, C.

    1985-01-01

    Work on cerebral uptake and organ kinetics of amphetamine derivatives has led to the clinical use of N-isopropyl amphetamine (IMP). Due to the fact that there is only 5 to 10% cerebral uptake relatively high amounts of the I 123 labelled tracer have to be administered resulting in high costs. Above that, it extensive pulmonary retention leads to a high radiation burden to this organ. In this chapter other tracers with superior properties for brain imaging are evaluated. Five amphetamine derivatives namely N-isopropyl amphetamine (IMP), fenetylline, pentyl amphetamine, benzyl amphetamine, and N-sec. butyl amphetamine (BMP) were tested. The experimental series consisted of wistar rats in which I-123 was labelled to these derivatives. BMP appeared to be superior in functional brain imaging. (Auth.)

  17. Cardiovascular Complications of Acute Amphetamine Abuse

    Science.gov (United States)

    Bazmi, Elham; Mousavi, Farinaz; Giahchin, Leila; Mokhtari, Tahmineh; Behnoush, Behnam

    2017-01-01

    Objectives This study aimed to evaluate cardiovascular complications among patients who abuse amphetamines. Methods This cross-sectional study took place between April 2014 and April 2015 among 3,870 patients referred to the Toxicology Emergency Department of Baharlou Hospital, Tehran University of Medical Sciences, Tehran, Iran. Those with clinical signs of drug abuse and positive urine screening tests were included in the study, while cases of chronic abuse were excluded. Cardiac complications were evaluated via electrocardiography (ECG) and transthoracic echocardiography. Results A total of 230 patients (5.9%) had a history of acute amphetamine abuse and positive urine tests. Of these, 32 patients (13.9%) were <20 years old and 196 (85.2%) were male. In total, 119 (51.7%) used amphetamine and methamphetamine compounds while 111 (48.3%) used amphetamines with morphine or benzodiazepines. The most common ECG finding was sinus tachycardia (43.0%), followed by sinus tachycardia plus a prolonged QT interval (34.3%). Mean creatine kinase-MB and troponin I levels were 35.9 ± 4.3 U/mL and 0.6 ± 0.2 ng/mL, respectively. A total of 60 patients (26.1%) were admitted to the Intensive Care Unit. The majority (83.3%) of these patients had normal echocardiography results. The mean aortic root diameter (ARD) was 27.2 ± 2.8 mm. Abnormalities related to the ARD were found in 10 patients (16.7%), three of whom subsequently died. Conclusion According to these findings, cardiac complications were common among Iranian patients who abuse amphetamines, although the majority of patients had normal echocardiography and ECG findings. PMID:28417026

  18. Detection and diagnostic interpretation of amphetamines in hair.

    Science.gov (United States)

    Nakahara, Y

    1995-01-05

    A review with 22 references on detection and incorporation of amphetamines in hair is presented. This review deals with the detection, incorporation into hair, behavior in the hair shaft, confirmation of past drug use and diagnosis of dependence mainly regarding amphetamine and methamphetamine, along with methoxyphenamine, methylenedioxymethamphetamine, bromomethamphetamine, deprenyl, benzphetamine, fenproporex and mefenorex. First, pretreatment, extraction and analytical methods for amphetamines in hair using immunoassay, HPLC and GC/MS are discussed. This is followed by sections describing the animal experiments, incorporation rates of amphetamines from blood to hair and relationship between drug history and drug distribution in hair. Finally, the diagnosis of amphetamine dependence and confirmation of methamphetamine baby by hair analysis is discussed. The paper concludes with a brief outlook.

  19. Comparison of periodontal manifestations in amphetamine and opioids' consumers

    Directory of Open Access Journals (Sweden)

    Masoome Eivazi

    2016-03-01

    Full Text Available Background: Drug abuse is one of the most important etiologic and deteriorating factors in periodontal disease. Amphetamines and opioids, the most commonly used drugs worldwide, play an important role in this regard. The aim of this study was to compare the periodontal status of amphetamines and opioids consumers in Kermanshah city, Iran in 1393. Methods: Three drug rehabilitation clinics were selected randomly in Kermanshah. According to inclusion and exclusion criteria, 20 amphetamine consumers and 20 opioid consumers were selected randomly and participated in this study. A questionnaire for drug use and periodontal variables was designed. The collected data were entered into SPSS-18 software and Mann-Whitney and t-test were used for statistical analysis. Results: Pocket depth, gingival index and gingival bleeding in amphetamines users were more than those in opioids consumers (P<0.021. Plaque index and gingival recession in opioids users were more than those of amphetamines consumers (P<0.001. The number of periodontal disease cases in amphetamines group were 13 persons (65% and in opioids group 8 persons (40%. Conclusion: Our study showed that periodontal hygine in amphetamine consumers was worse than opioid consumers.

  20. Metabolic production of amphetamine following multidose administration of clobenzorex.

    Science.gov (United States)

    Baden, K L; Valtier, S; Cody, J T

    1999-10-01

    The interpretation of urine drug-testing results can have important forensic and legal implications. In particular, drugs that are metabolized to amphetamine or methamphetamine or both pose significant concerns. In this study, clobenzorex, an anorectic drug that is metabolized to d-amphetamine, was administered to five subjects. Each subject took 30 mg daily for seven days, and individual urine samples were collected ad lib for 14 days beginning on the first day the drug was administered. Urine pH, specific gravity, and creatinine values were determined for each sample. Gas chromatography-mass spectrometry (GC-MS) was used to determine the excretion profile of amphetamine and clobenzorex using a standard procedure for amphetamines with additional monitoring of ions at m/z 118, 125, and 364 for the detection of clobenzorex. Peak concentrations of amphetamine were found at 82 to 168 h after the first dose and ranged from approximately 2900 to 4700 ng/mL amphetamine. The use of a regioisomer (3-Cl-benzylamphetamine) as internal standard allowed for accurate quantitation of the parent drug. Peak concentrations of clobenzorex were found at 50 to 120 h after the first dose and ranged from approximately 8 to 47 ng/mL clobenzorex. However, in many samples, clobenzorex was not detected at all. This analysis revealed that the metabolite, (amphetamine) is present in much higher concentrations than the parent compound, clobenzorex. Yet even at peak amphetamine concentrations, the parent was not always detected (limit of detection 1 ng/mL). Thus, in the interpretation of amphetamine-positive drug-testing results, the absence of clobenzorex in the urine sample does not exclude the possibility of its use.

  1. Neurotoxicity of drugs of abuse - the case of methylenedioxy amphetamines (MDMA, ecstasy ), and amphetamines

    Science.gov (United States)

    Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2009-01-01

    Ecstasy (MDMA, 3,4-methylendioxymethamphetamine) and the stimulants methamphetamine (METH, speed) and amphetamine are popular drugs among young people, particularly in the dance scene. When given in high doses both MDMA and the stimulant amphetamines are clearly neurotoxic in laboratory animals. MDMA causes selective and persistent lesions of central serotonergic nerve terminals, whereas amphetamines damage both the serotonergic and dopaminergic systems. In recent years, the question of ecstasy-induced neurotoxicity and possible functional sequelae has been addressed in several studies in drug users. Despite large methodological problems, the bulk of evidence suggests residual alterations of serotonergic transmission in MDMA users, although at least partial recovery may occur after long-term abstinence. However, functional sequelae may persist even after longer periods of abstinence. To date, the most consistent findings associate subtle cognitive impairments with ecstasy use, particularly with memory. In contrast, studies on possible long-term neurotoxic effects of stimulant use have been relatively scarce. Preliminary evidence suggests that alterations of the dopaminergic system may persist even after years of abstinence from METH, and may be associated with deficits in motor and cognitive performance. In this paper, we will review the literature focusing on human studies. PMID:19877498

  2. Illegal or legitimate use? Precursor compounds to amphetamine and methamphetamine.

    Science.gov (United States)

    Musshoff, F

    2000-02-01

    The interpretation of methamphetamine and amphetamine positive test results in biological samples is a challenge to clinical and forensic toxicology for several reasons. The effects of pH and dilution of urine samples and the knowledge about legitimate and illicit sources have to be taken into account. Besides a potentially legal prescription of amphetamines, many substances metabolize to methamphetamine or amphetamine in the body: amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Especially the knowledge of potential origins of methamphetamine and amphetamine turns out to be very important to prevent a misinterpretation of the surrounding circumstances and to prove illegal drug abuse. In this review, potential precursor compounds are described, including their medical use and major clinical effects and their metabolic profiles, as well as some clues which help to identify the sources.

  3. Amphetamines and pH-shift agents for brain imaging

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Winkler, C.

    1986-01-01

    This book gives a review of the results of experimental and clinical research on both I-amphetamine derivatives and pH-shift agents. Virtually all relevant working groups from the USA and Europe have contributed to this volume. The pharmacology of amphetamine and the corresponding receptor theories are described in detail, whereas other chapters deal with the labeling as well as the metabolic process of this drug. In addition to this, new amphetamine derivatives are presented together with other essential products which play a significant role in scintigraphy of the brain function. Finally, there are two chapters on instrumentation problems followed by eight contributions on the clinical results of amphetamine scintigraphy in cerebral vascular diseases, epilepsy, migraine and brain tumors.

  4. Effects of serotonin (5-HT)1B receptor ligands on amphetamine-seeking behavior in rats.

    Science.gov (United States)

    Miszkiel, Joanna; Przegaliński, Edmund

    2013-01-01

    Numerous studies have indicated that serotonin (5-HT)1B receptor ligands affect the behavioral effects of psychostimulants (cocaine, amphetamine), including the reinforcing activities of these drugs. To substantiate a role for those receptors in incentive motivation for amphetamine, we used the extinction/reinstatement model to examine the effects of the 5-HT1B receptor ligands on the reinstatement of extinguished amphetamine-seeking behavior. Rats trained to self-administer amphetamine (0.06 mg/kg/infusion) subsequently underwent the extinction procedure. These rats were then tested for the amphetamine-primed or amphetamine-associated cue-induced reinstatement of extinguished amphetamine-seeking behavior. The 5-HT1B receptor antagonist SB 216641 (5-7.5 mg/kg) attenuated the amphetamine (1.5 mg/kg)- and the amphetamine-associated cue combined with the threshold dose of amphetamine (0.5 mg/kg)-induced reinstatement of amphetamine-seeking behavior. The 5-HT1B receptor agonist CP 94253 (1.25-5 mg/kg) also inhibited the amphetamine-seeking behavior induced by amphetamine (1.5 mg/kg) but not by the cue combined with the threshold dose of amphetamine. The inhibitory effect of CP94253 on amphetamine-seeking behavior remained unaffected by the 5-HT1B receptor antagonist. Our results indicate that tonic activation of 5-HT1B receptors is involved in amphetamine- and cue-induced reinstatement of amphetamine-seeking behavior and that the inhibitory effects of 5-HT1B receptor antagonists on these phenomena are directly related to the motivational aspects of amphetamine abuse. The inhibitory effect of CP 94253 on amphetamine-seeking behavior seems to be unrelated to 5-HT1B receptor activation and may result from a general reduction of motivation.

  5. Brain SPECT with iodine-123-amphetamine in amyotrophic lateral sclerosis

    International Nuclear Information System (INIS)

    Boettger, I.G.; Ludolph, A.C.; Elger, C.E.; Lottes, G.

    1988-01-01

    The study of 17 patients with ALS by 123 I-amphetamine (BIMP) SPECT revealed reduced CBF/amphetamine uptake correlation with the clinical status and course of the disease. ALS appears to involve fronto-temporal structures/functions in the early stage finally leading to generalization with the exclusion of the cerebellum. Thus, in ALS an involvement of also other than only motor cerebral structures/functions, which may be reversible, has to be considered. (orig.)

  6. Amphetamine, past and present--a pharmacological and clinical perspective.

    Science.gov (United States)

    Heal, David J; Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-06-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine's diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine's distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.

  7. Amphetamine Positive Urine Toxicology Screen Secondary to Atomoxetine

    Directory of Open Access Journals (Sweden)

    Joshua L. Fenderson

    2013-01-01

    Full Text Available The aim of this paper is to report the first case of atomoxetine leading to false-positive urine drug screen. An otherwise healthy 27-year-old female with a history of attention deficit hyperactivity disorder (ADHD treated with atomoxetine had an acute onset tonic-clonic seizure. On arrival to the hospital, a urine toxicological drug screen with immunochemical cloned enzyme donor immunoassay (CEDIA was performed. Results were positive for amphetamines; however, the presence of these substances could not be confirmed with urine gas chromatography-mass spectrometry (GC-MS. She denied any illicit drug use, herbal medications, or supplements, and her other prescription medications have not been previously known to cause a false-positive result for amphetamines. While stimulant treatments for ADHD could certainly result in a positive result on urine screen for amphetamines, there have been no reports of false-positive results for amphetamines secondary to patients using atomoxetine. We implicate atomoxetine, and/or its metabolites, as a compound or compounds which may interfere with urine drug immunoassays leading to false-positive results for amphetamines CEDIA assays.

  8. Effects of amphetamine administration on neurogenesis in adult rats

    Directory of Open Access Journals (Sweden)

    Tomasz Stępień

    2017-12-01

    Full Text Available In our study expression of phospho-(Ser-10-histone H3 (pH3S10, a marker for the early stage of neurogenesis, and cellular early response genes were investigated using c-Fos protein as an example of a transcription factor in the neurogenic process in rats. Neurogenesis in the adult brain is regulated by endo- and exogenous factors, which influence the proliferation potential of progenitor cells and accelerate the dendritic development of newborn neurons. D-amphetamine, a psychoactive substance, is one of the exogenous factors able to influence the process of neurogenesis. The rats were injected with D-amphetamine at a dose of 1.5 mg/kg/body weight (b.w. under one administration scheme. Analysis of the pH3S10 and c-Fos expression levels in the group of D-amphetamine administered rats provided evidence of enhanced expression of these proteins in the regions of neurogenesis occurrence in rats. However, conclusions concerning stimulant effects of amphetamine on neurogenesis should be formulated with great caution, taking into account amphetamine dosage and the administration scheme. It should also be remembered that doses of psychoactive substances used in animal models can be lethal to humans.

  9. Amphetamine, past and present – a pharmacological and clinical perspective

    Science.gov (United States)

    Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-01-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine’s diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine’s distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed. PMID:23539642

  10. Amphetamines and pH-shift agents for brain imaging: Basic research and clinical results

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Winkler, C.

    1986-01-01

    This book contains 18 selections. Some of the titles are: Labelling of amphetamines with /sup 123/I: Receptors for amphetamines; New amphetamine derivatives; Potential new approaches for the development of brain imaging agents for single-photon applications; and IM SPECT with the pinhole collimator.

  11. The Neuropsychology of Amphetamine and Opiate Dependence: Implications for Treatment

    Science.gov (United States)

    Sahakian, Barbara J

    2013-01-01

    Chronic use of amphetamines and/or opiates has been associated with a wide range of cognitive deficits, involving domains of attention, inhibitory control, planning, decision-making, learning and memory. Although both amphetamine and opiate users show marked impairment in various aspects of cognitive function, the impairment profile is distinctly different according to the substance of abuse. In light of evidence showing that cognitive impairment in drug users has a negative impact on treatment engagement and efficacy, we review substance-specific deficits on executive and memory function, and discuss possibilities to address these during treatment intervention. PMID:17690986

  12. Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives.

    Science.gov (United States)

    Kraemer, Thomas; Maurer, Hans H

    2002-04-01

    This paper reviews the toxicokinetics of amphetamines. The designer drugs MDA (methylenedioxy-amphetamine, R,S-1-(3;,4;-methylenedioxyphenyl)2-propanamine), MDMA (R,S-methylenedioxymethamphetamine), and MDE (R,S-methylenedioxyethylamphetamine), as well as BDB (benzodioxolylbutanamine; R,S-1-(1;,3;-benzodioxol-5;-yl)-2-butanamine or R,S-1-(3;,4;-methylenedioxyphenyl)-2-butanamine) and MBDB (R,S-N-methyl-benzodioxolylbutanamine), were taken into consideration, as were the following N-alkylated amphetamine derivatives: amphetaminil, benzphetamine, clobenzorex, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, methamphetamine, prenylamine, and selegiline. English-language publications from 1995 to 2000 were reviewed. Papers describing identification of metabolites or cytochrome P450 isoenzyme-dependent metabolism and papers containing pharmacokinetic/toxicokinetic data were considered and summarized. The implications of toxicokinetics for toxicologic assessment or for interpretation in forensic cases are discussed.

  13. Ab Initio Calculations and Raman and SERS Spectral Analyses of Amphetamine Species

    DEFF Research Database (Denmark)

    Berg, Rolf W.; Nørbygaard, Thomas; White, Peter C.

    2011-01-01

    For the first time, the differences between the spectra of amphetamine and amphetamine-H+ and between different conformers are thoroughly studied by ab initio model calculations, and Raman and surface-enhanced Raman spectroscopy (SERS) spectra are measured for different species of amphetamine....... The spectra of amphetamine and amphetamine-H+ sampleswere obtained and assigned according to a comparison of the experimental spectra and the ab initio MO calculations, performed using the Gaussian 03W program (Gaussian, Inc., Pittsburgh, PA). The analyses were based on complete geometry minimization...

  14. Amphetamine Containing Dietary Supplements and Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Julio Perez-Downes

    2016-01-01

    Full Text Available Weight loss is one of the most researched and marketed topics in American society. Dietary regimens, medications that claim to boost the metabolism, and the constant pressure to fit into society all play a role in our patient’s choices regarding new dietary products. One of the products that are well known to suppress appetite and cause weight loss is amphetamines. While these medications suppress appetite, most people are not aware of the detrimental side effects of amphetamines, including hypertension, tachycardia, arrhythmias, and in certain instances acute myocardial infarction. Here we present the uncommon entity of an acute myocardial infarction due to chronic use of an amphetamine containing dietary supplement in conjunction with an exercise regimen. Our case brings to light further awareness regarding use of amphetamines. Clinicians should have a high index of suspicion of use of these substances when young patients with no risk factors for coronary artery disease present with acute arrhythmias, heart failure, and myocardial infarctions.

  15. Brain SPECT with 123I-isopropyl amphetamine in epilepsy

    International Nuclear Information System (INIS)

    Biersack, H.J.; Reske, S.N.; Rasche, A.; Reichmann, K.; Winkler, C.

    1983-01-01

    Ten patients were studied with N-isopropyl I-123 p-iodoamphetamine. Single photon emission computed tomography (SPECT) was carried out by hand of a rotating gamma camera system (Gammatome T9000/CGR, high resolution collimator). During 1 rotation (360 0 ) 64 frames (4k matrix) were acquired within 20 min 1 hour after injection of 6.5 mCi I-123 labeled amphetamine. The content of I-124 was less than 2%. After reconstruction of transverse slices coronar and sagittal reconstructions were rapidly performed using an array processor. Nine patients suffered from epilepsy and one from severe migraine. Excellent differentiation between gray and white matter of the cerebral cortex and the basal ganglia was evident in all of the cases. In 2 out of 3 patients with epilepsy and negative CT results SPECT revealed circumscribed areas with increased amphetamine uptake in accordance with the EEG findings. In 4 out of 6 cases with positive CT findings SPECT lesions with diminished amphetamine uptake could be established. One patient with severe migraine showed focal increased amphetamine uptake in accordance with the respective clinical results. (orig.)

  16. Cannabis and Amphetamine Use Among Adolescents in Five Asian Countries

    Directory of Open Access Journals (Sweden)

    Karl Peltzer

    2017-12-01

    Conclusions: Our preliminary results show the importance of personal attributes such as mental distress and environmental stressors on lifetime cannabis and lifetime amphetamine use. Future prospective studies are needed to identify causal relationships among personal attributes, parental attributes, environmental stressors, and illicit substance use.

  17. Cardiovascular Complications of Acute Amphetamine Abuse; Cross-sectional study

    Directory of Open Access Journals (Sweden)

    Elham Bazmi

    2017-03-01

    Full Text Available Objectives: This study aimed to evaluate cardiovascular complications among patients who abuse amphetamines. Methods: This cross-sectional study took place between April 2014 and April 2015 among 3,870 patients referred to the Toxicology Emergency Department of Baharlou Hospital, Tehran University of Medical Sciences, Tehran, Iran. Those with clinical signs of drug abuse and positive urine screening tests were included in the study, while cases of chronic abuse were excluded. Cardiac complications were evaluated via electrocardiography (ECG and transthoracic echocardiography. Results: A total of 230 patients (5.9% had a history of acute amphetamine abuse and positive urine tests. Of these, 32 patients (13.9% were <20 years old and 196 (85.2% were male. In total, 119 (51.7% used amphetamine and methamphetamine compounds while 111 (48.3% used amphetamines with morphine or benzodiazepines. The most common ECG finding was sinus tachycardia (43.0%, followed by sinus tachycardia plus a prolonged QT interval (34.3%. Mean creatine kinase-MB and troponin I levels were 35.9 ± 4.3 U/mL and 0.6 ± 0.2 ng/mL, respectively. A total of 60 patients (26.1% were admitted to the Intensive Care Unit. The majority (83.3% of these patients had normal echocardiography results. The mean aortic root diameter (ARD was 27.2 ± 2.8 mm. Abnormalities related to the ARD were found in 10 patients (16.7%, three of whom subsequently died. Conclusion: According to these findings, cardiac complications were common among Iranian patients who abuse amphetamines, although the majority of patients had normal echocardiography and ECG findings.

  18. Enhanced appetitive conditioning following repeated pretreatment with d-amphetamine.

    Science.gov (United States)

    Harmer, C J; Phillips, G D

    1998-07-01

    The behavioural response to psychomotor stimulants is augmented with repeated exposure to these drugs. Enhanced stimulated dopamine overflow within the nucleus accumbens and amygdala has been found to accompany this behavioural sensitization. In the present experiment, rats received 2 mg/kg d-amphetamine or 1 ml/kg physiological saline once per day for 5 days. Five days later, a behavioural assay confirmed that prior repeated d-amphetamine treatment markedly enhanced the locomotor activating effects of a d-amphetamine (0.5 mg/kg, i.p.) challenge. Training on a Pavlovian conditioning task began six days subsequently. In Stage 1, a stimulus (light or tone, S-) was presented negatively correlated with a sucrose reward. In Stage 2, presentation of the alternative counterbalanced stimulus (light or tone, S+) was paired with the availability of a 10% sucrose solution. There were no differences between the two groups in their response to the the S- stimulus. However, sensitized animals showed a selective enhancement in the acquisition of conditioned responding to S+, relative to vehicle-injected controls. No differences in behaviour were recorded during the prestimulus periods, nor during presentations of sucrose. Levels of activity within the operant chamber extraneous to alcove approach were also similar in both groups of animals. The conditioned instrumental efficacy of S+, relative to S- was assessed in Stage 3, in which stimulus availability was made contingent on a novel lever-pressing response. Both groups showed a similar preference for the S+ over the S- stimulus. Hence, rats sensitized by prior repeated d-amphetamine showed enhanced appetitive Pavlovian conditioning, without subsequent effect on conditioned reward efficacy. These data are discussed in light of possible changes in mesoamygdaloid dopamine functioning.

  19. Amphetamine activates Rho GTPase signaling to mediate dopamine transporter internalization and acute behavioral effects of amphetamine

    Science.gov (United States)

    Wheeler, David S.; Underhill, Suzanne M.; Stolz, Donna B.; Murdoch, Geoffrey H.; Thiels, Edda; Romero, Guillermo; Amara, Susan G.

    2015-01-01

    Acute amphetamine (AMPH) exposure elevates extracellular dopamine through a variety of mechanisms that include inhibition of dopamine reuptake, depletion of vesicular stores, and facilitation of dopamine efflux across the plasma membrane. Recent work has shown that the DAT substrate AMPH, unlike cocaine and other nontransported blockers, can also stimulate endocytosis of the plasma membrane dopamine transporter (DAT). Here, we show that when AMPH enters the cytoplasm it rapidly stimulates DAT internalization through a dynamin-dependent, clathrin-independent process. This effect, which can be observed in transfected cells, cultured dopamine neurons, and midbrain slices, is mediated by activation of the small GTPase RhoA. Inhibition of RhoA activity with C3 exotoxin or a dominant-negative RhoA blocks AMPH-induced DAT internalization. These actions depend on AMPH entry into the cell and are blocked by the DAT inhibitor cocaine. AMPH also stimulates cAMP accumulation and PKA-dependent inactivation of RhoA, thus providing a mechanism whereby PKA- and RhoA-dependent signaling pathways can interact to regulate the timing and robustness of AMPH’s effects on DAT internalization. Consistent with this model, the activation of D1/D5 receptors that couple to PKA in dopamine neurons antagonizes RhoA activation, DAT internalization, and hyperlocomotion observed in mice after AMPH treatment. These observations support the existence of an unanticipated intracellular target that mediates the effects of AMPH on RhoA and cAMP signaling and suggest new pathways to target to disrupt AMPH action. PMID:26553986

  20. Amphetamine-type medicines: a review of pharmacokinetics, pharmacodynamics, and toxicological aspects.

    Science.gov (United States)

    Mariotti, Kristianee C; Rossato, Luciana G; Fröehlich, Pedro E; Limberger, Renata P

    2013-11-01

    Amphetamine-like drugs are sympathomimetic agents with marked central and peripheral stimulant properties. Despite the street illegal drugs such as amphetamine and ecstasy, some amphetamine-like compounds are also legally marketed under medical prescription in the treatment of attention deficit-hyperactivity disorder (methylphenidate) and obesity/overweight (fenproporex and diethylpropione). However, similar with what happens with their illicit analogues, therapeutic amphetamine-like drugs also share important toxicological risks. Although methylphenidate is considered the first choice in the treatment of attention deficit-hyperactivity disorder, its high popularity among teenagers and children is raising concern in the medical community. Regarding weight-loss purposes, the use of amphetamine-like compounds are very controversial, though. Thus, the present review will address pharmacokinetic, pharmacodynamic, and toxicological aspects of amphetamine-like compounds used with therapeutic aims.

  1. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis

    Directory of Open Access Journals (Sweden)

    Natalia M. Branis

    2015-01-01

    Full Text Available Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35–7.45, bicarbonate 16 mmol/L (22–29 mmol/L, and anion gap 19 mmol/L (8–16 mmol/L. Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  2. Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Patrick C. Dolder

    2017-09-01

    Full Text Available Rationale: Lisdexamfetamine is a prodrug of D-amphetamine used for the treatment of attention-deficit/hyperactivity disorder (ADHD. Lisdexamfetamine is thought to have a prolonged pharmacokinetic profile compared with oral D-amphetamine, possibly associated with lower drug liking and a lower risk of oral misuse. However, differences in the pharmacokinetics and pharmacodynamics of lisdexamfetamine and D-amphetamine have not been directly compared.Methods: Equimolar doses of D-amphetamine (40 mg and lisdexamfetamine (100 mg, and placebo were administered in 24 healthy subjects in a randomized, double-blind, placebo-controlled, cross-over study. Plasma concentrations of amphetamine, subjective effects, and vital signs were repeatedly assessed. The pharmacokinetic parameters were determined using compartmental modeling.Results: The increase in plasma concentrations of amphetamine had a 0.6 ± 0.6 h (mean ± SD longer lag time and reached peak levels 1.1 ± 1.5 h later after lisdexamfetamine administration compared with D-amphetamine administration, but no differences in maximal concentrations or total exposure (AUC were found between the two treatments. Consistent with the pharmacokinetics, the subjective and cardiovascular stimulant effects of lisdexamfetamine also occurred later compared with D-amphetamine. However, no differences in peak ratings of potentially abuse-related subjective drug effects (e.g., drug liking, drug high, stimulation, happy, well-being, and self-confidence were observed after lisdexamfetamine administration compared with D-amphetamine administration. Lisdexamfetamine and D-amphetamine also produced similar peak increases in mean arterial blood pressure, heart rate, body temperature, pupil size, and adverse effects.Conclusion: The pharmacokinetics and pharmacodynamics of lisdexamfetamine are similar to D-amphetamine administered 1h later. Lisdexamfetamine is likely associated with a similar risk of oral abuse as D-amphetamine

  3. Amphetamine-induced psychosis - a separate diagnostic entity or primary psychosis triggered in the vulnerable?

    Directory of Open Access Journals (Sweden)

    Bramness Jørgen G

    2012-12-01

    Full Text Available Abstract Use of amphetamine and methamphetamine is widespread in the general population and common among patients with psychiatric disorders. Amphetamines may induce symptoms of psychosis very similar to those of acute schizophrenia spectrum psychosis. This has been an argument for using amphetamine-induced psychosis as a model for primary psychotic disorders. To distinguish the two types of psychosis on the basis of acute symptoms is difficult. However, acute psychosis induced by amphetamines seems to have a faster recovery and appears to resolve more completely compared to schizophrenic psychosis. The increased vulnerability for acute amphetamine induced psychosis seen among those with schizophrenia, schizotypal personality and, to a certain degree other psychiatric disorders, is also shared by non-psychiatric individuals who previously have experienced amphetamine-induced psychosis. Schizophrenia spectrum disorder and amphetamine-induced psychosis are further linked together by the finding of several susceptibility genes common to both conditions. These genes probably lower the threshold for becoming psychotic and increase the risk for a poorer clinical course of the disease. The complex relationship between amphetamine use and psychosis has received much attention but is still not adequately explored. Our paper reviews the literature in this field and proposes a stress-vulnerability model for understanding the relationship between amphetamine use and psychosis.

  4. Amphetamine-induced psychosis - a separate diagnostic entity or primary psychosis triggered in the vulnerable?

    Science.gov (United States)

    2012-01-01

    Use of amphetamine and methamphetamine is widespread in the general population and common among patients with psychiatric disorders. Amphetamines may induce symptoms of psychosis very similar to those of acute schizophrenia spectrum psychosis. This has been an argument for using amphetamine-induced psychosis as a model for primary psychotic disorders. To distinguish the two types of psychosis on the basis of acute symptoms is difficult. However, acute psychosis induced by amphetamines seems to have a faster recovery and appears to resolve more completely compared to schizophrenic psychosis. The increased vulnerability for acute amphetamine induced psychosis seen among those with schizophrenia, schizotypal personality and, to a certain degree other psychiatric disorders, is also shared by non-psychiatric individuals who previously have experienced amphetamine-induced psychosis. Schizophrenia spectrum disorder and amphetamine-induced psychosis are further linked together by the finding of several susceptibility genes common to both conditions. These genes probably lower the threshold for becoming psychotic and increase the risk for a poorer clinical course of the disease. The complex relationship between amphetamine use and psychosis has received much attention but is still not adequately explored. Our paper reviews the literature in this field and proposes a stress-vulnerability model for understanding the relationship between amphetamine use and psychosis. PMID:23216941

  5. Interactions between radiation and amphetamine in taste aversion learning and the role of the area postrema in amphetamine-induced conditioned taste aversions

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.; Lee, J.

    1987-01-01

    Three experiments were run to assess the role of the area postrema in taste aversion learning resulting from combined treatment with subthreshold unconditioned stimuli and in the acquisition of an amphetamine-induced taste aversion. In the first experiment, it was shown that combined treatment with subthreshold radiation (15 rad) and subthreshold amphetamine (0.5 mg/kg, IP) resulted in the acquisition of a taste aversion. The second experiment showed that lesions of the area postrema blocked taste aversion learning produced by two subthreshold doses of amphetamine. In the third experiment, which looked at the dose-response curve for amphetamine-induced taste aversion learning in intact rats and rats with area postrema lesions, it was shown that both groups of rats acquired taste aversions following injection of amphetamine, although the rats with lesions showed a less severe aversion than the intact rats. The results are interpreted as indicating that amphetamine-induced taste aversion learning may involve area postrema-mediated mechanisms, particularly at the lower doses, but that an intact area postrema is not a necessary condition for the acquisition of an amphetamine-induced taste aversion

  6. Crayfish Self-Administer Amphetamine in a Spatially Contingent Task

    Directory of Open Access Journals (Sweden)

    Udita Datta

    2018-05-01

    Full Text Available Natural reward is an essential element of any organism’s ability to adapt to environmental variation. Its underlying circuits and mechanisms guide the learning process as they help associate an event, or cue, with the perception of an outcome’s value. More generally, natural reward serves as the fundamental generator of all motivated behavior. Addictive plant alkaloids are able to activate this circuitry in taxa ranging from planaria to humans. With modularly organized nervous systems and confirmed vulnerabilities to human drugs of abuse, crayfish have recently emerged as a compelling model for the study of the addiction cycle, including psychostimulant effects, sensitization, withdrawal, reinstatement, and drug reward in conditioned place preference paradigms. Here we extend this work with the demonstration of a spatially contingent, operant drug self-administration paradigm for amphetamine. When the animal enters a quadrant of the arena with a particular textured substrate, a computer-based control system delivers amphetamine through an indwelling fine-bore cannula. Resulting reward strength, dose-response, and the time course of operant conditioning were assessed. Individuals experiencing the drug contingent on their behavior, displayed enhanced rates of operant responses compared to that of their yoked (non-contingent counterparts. Application of amphetamine near the supra-esophageal ganglion elicited stronger and more robust increases in operant responding than did systemic infusions. This work demonstrates automated implementation of a spatially contingent self-administration paradigm in crayfish, which provides a powerful tool to explore comparative perspectives in drug-sensitive reward, the mechanisms of learning underlying the addictive cycle, and phylogenetically conserved vulnerabilities to psychostimulant compounds.

  7. Stability studies of amphetamine and ephedrine derivatives in urine.

    Science.gov (United States)

    Jiménez, C; de la Torre, R; Ventura, M; Segura, J; Ventura, R

    2006-10-20

    Knowledge of the stability of drugs in biological specimens is a critical consideration for the interpretation of analytical results. Identification of proper storage conditions has been a matter of concern for most toxicology laboratories (both clinical and forensic), and the stability of drugs of abuse has been extensively studied. This concern should be extended to other areas of analytical chemistry like antidoping control. In this work, the stability of ephedrine derivatives (ephedrine, norephedrine, methylephedrine, pseudoephedrine, and norpseudoephedrine), and amphetamine derivatives (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA)) in urine has been studied. Spiked urine samples were prepared for stability testing. Urine samples were quantified by GC/NPD or GC/MS. The homogeneity of each batch of sample was verified before starting the stability study. The stability of analytes was evaluated in sterilized and non-sterilized urine samples at different storage conditions. For long-term stability testing, analyte concentration in urine stored at 4 degrees C and -20 degrees C was determined at different time intervals for 24 months for sterile urine samples, and for 6 months for non-sterile samples. For short-term stability testing, analyte concentration was evaluated in liquid urine stored at 37 degrees C for 7 days. The effect of repeated freezing (at -20 degrees C) and thawing (at room temperature) was also studied in sterile urine for up to three cycles. No significant loss of the analytes under study was observed at any of the investigated conditions. These results show the feasibility of preparing reference materials containing ephedrine and amphetamine derivatives to be used for quality control purposes.

  8. Development and validation of the Amphetamine-Type Stimulants Motive Questionnaire in a clinical population

    NARCIS (Netherlands)

    Thurn, D.; Kuntsche, E.N.; Weber, J.A.; Wolstein, J.

    2017-01-01

    Approximately 35.7 million people world-wide use amphetamine-type stimulants (ATS) leading to a high demand for effective treatment. Understanding the motives behind ATS use is a necessary basis for preventive and therapeutic treatment. The objective of this study is to develop the Amphetamine-Type

  9. Literature Review: Update on Amphetamine Neurotoxicity and Its Relevance to the Treatment of ADHD

    Science.gov (United States)

    Advokat, Claire

    2007-01-01

    Objective: A review of amphetamine treatment for attention-deficit/hyperactivity disorder (ADHD) was conducted, to obtain information on the long-term neurological consequences of this therapy. Method: Several databases were accessed for research articles on the effects of amphetamine in the brain of laboratory animals and ADHD diagnosed…

  10. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine inhalers regarded as prescription drugs. (a) Recurring reports of abuse and misuse of methamphetamine (also...

  11. HIV Risk Behavior among Amphetamine Injectors at U.S. Syringe Exchange Programs

    Science.gov (United States)

    Braine, Naomi; Des Jarlais, Don C.; Goldblatt, Cullen; Zadoretzky, Cathy; Turner, Charles

    2005-01-01

    The goal of this study was to compare HIV risk behaviors of amphetamine and non-amphetamine injectors at syringe exchange programs (SEP) in the United States and to identify factors associated with injection risk. This analysis is based on data from a random cross-section of participants at 13 SEPs in different parts of the country. All interviews…

  12. Effects of Amphetamine and β-Endorphin Fragments on Maze Performance in Rats

    NARCIS (Netherlands)

    Boer, S. de; Bohus, B.

    1990-01-01

    Fragments of β-endorphin and amphetamine cause similar effects in some tests of maze behavior in rats. The present study served to compare the influence of amphetamine and two β-endorphin fragments [β-endorphin (βE)-(2-9) and βE-(2-16)] on maze behavior in more detail. In Experiment I no significant

  13. Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine

    Science.gov (United States)

    Covey, Dan P.; Juliano, Steven A.; Garris, Paul A.

    2013-01-01

    Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent in the dorsal striatum. Specifically, amphetamine up-regulated vesicular dopamine release elicited by a short-duration train, which interrogates the readily releasable pool, but depleted release elicited by a long-duration train, which interrogates the reserve pool. These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses. A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only. We submit that amphetamine differentially targeting dopamine stores reconciles the paradoxical activation of tonic and phasic dopamine signaling. Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties. PMID:23671560

  14. Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not striatum.

    Science.gov (United States)

    Mattsson, Anna; Olson, Lars; Svensson, Torgny H; Schilström, Björn

    2007-11-01

    Cholinergic dysfunction has been implicated as a putative contributing factor in the pathogenesis of schizophrenia. Recently, we showed that cholinergic denervation of the neocortex in adult rats leads to a marked increase in the behavioral response to amphetamine. The main objective of this study was to investigate if the enhanced locomotor response to amphetamine seen after cortical cholinergic denervation was paralleled by an increased amphetamine-induced release of dopamine in the nucleus accumbens and/or striatum. The corticopetal cholinergic projections were lesioned by intraparenchymal infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of adult rats. Amphetamine-induced dopamine release in the nucleus accumbens or striatum was monitored by in vivo microdialysis 2 to 3 weeks after lesioning. We found that cholinergic denervation of the rat neocortex leads to a significantly increased amphetamine-induced dopamine release in the nucleus accumbens. Interestingly, the cholinergic lesion did not affect amphetamine-induced release of dopamine in the striatum. The enhanced amphetamine-induced dopamine release in the nucleus accumbens in the cholinergically denervated rats could be reversed by administration of the muscarinic agonist oxotremorine, but not nicotine, prior to the amphetamine challenge, suggesting that loss of muscarinic receptor stimulation is likely to have caused the observed effect. The results suggest that abnormal responsiveness of dopamine neurons can be secondary to cortical cholinergic deficiency. This, in turn, might be of relevance for the pathophysiology of schizophrenia and provides a possible link between cholinergic disturbances and alteration of dopamine transmission.

  15. Cannabis and Amphetamine Use Among Adolescents in Five Asian Countries

    OpenAIRE

    Karl Peltzer; Supa Pengpid

    2017-01-01

    Introduction: There has been a global increase in illicit drug use among young people. The aim of this study was to estimate the prevalence of lifetime cannabis and amphetamine use, as well as to explore factors associated with substance use among adolescents in five Asian countries: Iraq, Kuwait, Malaysia, Mongolia, and Vietnam. Methods: 38,941  school children (mean age 15.4 years, SD=1.5) completed the cross-sectional Global School-Based Student Health Survey (GSHS). Topics covered in t...

  16. Acute Demyelination in a Person with Amphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Serge Weis

    2011-01-01

    Full Text Available We report the case of a 31-year-old woman, admitted to the hospital for chest pain, dying a few days later from septic multiorgan failure, and showing at autopsy foci of acute demyelination in the occipital lobe. Gas chromatography/mass spectrometry analysis revealed the presence of amphetamine in the demyelinated area, which might be considered as the pathogenic agent, since other causes for demyelination could be excluded. This case represents the first report showing a demyelinating process due to a street drug.

  17. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Science.gov (United States)

    2010-10-01

    ... involving marijuana, cocaine, amphetamines, or PCP? 40.137 Section 40.137 Transportation Office of the... results involving marijuana, cocaine, amphetamines, or PCP? (a) As the MRO, you must verify a confirmed positive test result for marijuana, cocaine, amphetamines, and/or PCP unless the employee presents a...

  18. Amphetamine-like stimulant cessation in an abusing patient treated with bupropion.

    Science.gov (United States)

    Tardieu, S; Poirier, Y; Micallef, J; Blin, O

    2004-01-01

    Bupropion sustained release is considered to be a weak inhibitor of dopamine and serotonin reuptake. We report the case of an amphetamine-abusing patient who self-administered bupropion. Since 30 years, a 52-year-old women used amphetamine derivates. She explained her need for amphetamine use in order to perform daily activities. Recently, she decided to experiment with bupropion. She abruptly stopped taking clobenzorex and simultaneously started taking bupropion (150 mg/day). The seventh day she reported a concomitant intake of clobenzorex; this induced adverse effects. Whilst taking bupropion, she described experiencing an euthymic state without any compulsion to take amphetamine drugs and was able to perform daily activities. After stopping it, no symptoms of withdrawal were reported by the patient. This observation supports an another report suggesting that bupropion may be of help in weaning from amphetamine users and should be confirmed by clinical trials.

  19. Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice123

    Science.gov (United States)

    Storey, Granville P.; Heimbigner, Lauren; Walwyn, Wendy M.; Bamford, Nigel S.

    2016-01-01

    Abstract Corticostriatal signaling participates in sensitized responses to drugs of abuse, where short-term increases in dopamine availability provoke persistent, yet reversible, changes in glutamate release. Prior studies in mice show that amphetamine withdrawal promotes a chronic presynaptic depression in glutamate release, whereas an amphetamine challenge reverses this depression by potentiating corticostriatal activity in direct pathway medium spiny neurons. This synaptic plasticity promotes corticostriatal activity and locomotor sensitization through upstream changes in the activity of tonically active cholinergic interneurons (ChIs). We used a model of operant drug-taking behaviors, in which mice self-administered amphetamine through an in-dwelling catheter. Mice acquired amphetamine self-administration under fixed and increasing schedules of reinforcement. Following a period of abstinence, we determined whether nicotinic acetylcholine receptors modified drug-seeking behavior and associated alterations in ChI firing and corticostriatal activity. Mice responding to conditioned reinforcement showed reduced ChI and corticostriatal activity ex vivo, which paradoxically increased following an amphetamine challenge. Nicotine, in a concentration that increases Ca2+ influx and desensitizes α4β2*-type nicotinic receptors, reduced amphetamine-seeking behaviors following abstinence and amphetamine-induced locomotor sensitization. Nicotine blocked the depression of ChI firing and corticostriatal activity and the potentiating response to an amphetamine challenge. Together, these results demonstrate that nicotine reduces reward-associated behaviors following repeated amphetamine and modifies the changes in ChIs firing and corticostriatal activity. By returning glutamatergic activity in amphetamine self-administering mice to a more stable and normalized state, nicotine limits the depression of striatal activity in withdrawal and the increase in activity following

  20. Metabolism and disposition of N-(2-cyanoethyl)amphetamine (fenproporex) and amphetamine: study in the rat brain.

    Science.gov (United States)

    Coutts, R T; Nazarali, A J; Baker, G B; Pasutto, F M

    1986-06-01

    N-(2-Cyanoethyl)amphetamine (fenproporex, CE-AM) is a clinically used anorexiant claimed to be devoid of the stimulant properties associated with amphetamine (AM). This claim was inconsistent with preliminary studies conducted in our laboratories which indicated that CE-AM is metabolically dealkylated to AM to a considerable extent in the rat. Concentration-time profiles of CE-AM and its metabolites AM and 4-hydroxyamphetamine (4-OH-AM) in the rat brain were constructed after administration of CE-AM. Analyses of CE-AM, AM, and 4-OH-AM were performed by gas chromatography with electron-capture detection using pentafluorobenzoyl chloride (under aqueous conditions) as the derivatizing reagent. The half-life (t1/2) and the maximum concentration (Cmax) of AM after administration of CE-AM were calculated to be 2.04 and 0.56 times the respective t1/2 and Cmax obtained after an equimolar dose of AM. Significant differences in the profiles of 4-OH-AM were also observed. The Cmax of 4-OH-AM in rat brain after administration of CE-AM was nearly 4 times higher and the tmax (time at which concentration is maximum) 4 times lower than the respective Cmax and tmax values of 4-OH-AM observed after an equimolar dose of AM.

  1. Improvement of attention with amphetamine in low- and high-performing rats.

    Science.gov (United States)

    Turner, Karly M; Burne, Thomas H J

    2016-09-01

    Attentional deficits occur in a range of neuropsychiatric disorders, such as schizophrenia and attention deficit hyperactivity disorder. Psychostimulants are one of the main treatments for attentional deficits, yet there are limited reports of procognitive effects of amphetamine in preclinical studies. Therefore, task development may be needed to improve predictive validity when measuring attention in rodents. This study aimed to use a modified signal detection task (SDT) to determine if and at what doses amphetamine could improve attention in rats. Sprague-Dawley rats were trained on the SDT prior to amphetamine challenge (0.1, 0.25, 0.75 and 1.25 mg/kg). This dose range was predicted to enhance and disrupt cognition with the effect differing between individuals depending on baseline performance. Acute low dose amphetamine (0.1 and 0.25 mg/kg) improved accuracy, while the highest dose (1.25 mg/kg) significantly disrupted performance. The effects differed for low- and high-performing groups across these doses. The effect of amphetamine on accuracy was found to significantly correlate with baseline performance in rats. This study demonstrates that improvement in attentional performance with systemic amphetamine is dependent on baseline accuracy in rats. Indicative of the inverted U-shaped relationship between dopamine and cognition, there was a baseline-dependent shift in performance with increasing doses of amphetamine. The SDT may be a useful tool for investigating individual differences in attention and response to psychostimulants in rodents.

  2. Maintenance on naltrexone+amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys.

    Science.gov (United States)

    Moerke, Megan J; Banks, Matthew L; Cheng, Kejun; Rice, Kenner C; Negus, S Stevens

    2017-12-01

    Cocaine use disorder remains a significant public health issue for which there are no FDA-approved pharmacotherapies. Amphetamine maintenance reduces cocaine use in preclinical and clinical studies, but the mechanism of this effect is unknown. Previous studies indicate a role for endogenous opioid release and subsequent opioid receptor activation in some amphetamine effects; therefore, the current study examined the role of mu-opioid receptor activation in d-amphetamine treatment effects in an assay of cocaine-vs-food choice. Adult male rhesus monkeys with double-lumen intravenous catheters responded for concurrently available food pellets and cocaine injections (0-0.1mg/kg/injection) during daily sessions. Cocaine choice and overall reinforcement rates were evaluated during 7-day treatments with saline or test drugs. During saline treatment, cocaine maintained a dose-dependent increase in cocaine-vs.-food choice. The mu-opioid receptor agonist morphine (0.032-0.32mg/kg/h) dose-dependently increased cocaine choice and decreased rates of reinforcement. A dose of the mu-selective opioid receptor antagonist naltrexone (0.0032mg/kg/h) that completely blocked morphine effects had no effect on cocaine choice when it was administered alone, but it enhanced the effectiveness of a threshold dose of 0.032mg/kg/h amphetamine to decrease cocaine choice without also enhancing nonselective behavioral disruption by this dose of amphetamine. Conversely, the kappa-selective opioid antagonist norbinalorphimine did not enhance amphetamine effects on cocaine choice. These results suggest that amphetamine maintenance produces mu opioid-receptor mediated effects that oppose its anti-cocaine effects. Co-administration of naltrexone may selectively enhance amphetamine potency to decrease cocaine choice without increasing amphetamine potency to produce general behavioral disruption. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Differentiation of clobenzorex use from amphetamine abuse using the metabolite 4-hydroxyclobenzorex.

    Science.gov (United States)

    Valtier, S; Cody, J T

    2000-10-01

    Clobenzorex (Asenlix) is an anorectic drug metabolized by the body to amphetamine, thus causing difficulty in the interpretation of amphetamine-positive drug tests. Previous studies have shown the parent drug and several metabolites are excreted in urine. Clobenzorex itself has been detected for as long as 29 h postdose using a detection limit of 1 ng/mL. Despite this fact, several amphetamine-positive samples (> or = 500 ng/mL) contained no detectable clobenzorex. Thus, the absence of clobenzorex in the urine does not exclude the possibility of its use. To more definitively assess the possibility of clobenzorex use, evaluation of another metabolite was considered. One study reported the presence of unidentified hydroxy metabolites of clobenzorex for as long as amphetamine was detected in some subjects. To assess the viability of using a hydroxy metabolite to confirm the use of clobenzorex in samples containing amphetamine, 4-hydroxyclobenzorex was synthesized for this study. This metabolite proved to be easily detected and was typically found at levels higher than amphetamine in amphetamine-positive urines, long after clobenzorex itself was no longer detected. Samples obtained from a controlled single-dose study involving the administration of clobenzorex (30 mg) were analyzed for the presence of the 4-hydroxy metabolite. The analytical procedure used acid hydrolysis followed by liquid-liquid extraction and analysis with gas chromatography-mass spectrometry by monitoring ions at m/z 125, 330, and 364. 4-Hydroxyclobenzorex and its 3-Cl regioisomer were used in the identification and quantitation of the metabolite. Peak concentrations of 4-hydroxyclobenzorex were found at approximately 1:30-5:00 h postdose and ranged from approximately 5705 to 88,410 ng/mL. Most importantly, however, all samples that contained amphetamine at > or = 500 ng/mL also contained detectable amounts of this hydroxy metabolite (LOD 10 ng/mL), making it a valuable tool in differentiating use

  4. Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries

    International Nuclear Information System (INIS)

    Chen, Mei-Fang; Lai, Su-Yu; Kung, Po-Cheng; Lin, Yo-Cheng; Yang, Hui-I; Chen, Po-Yi; Liu, Ingrid Y.; Lua, Ahai Chang; Lee, Tony Jer-Fu

    2016-01-01

    The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O 2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100 μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8 Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine > methamphetamine > hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic

  5. The N terminus of monoamine transporters is a lever required for the action of amphetamines

    DEFF Research Database (Denmark)

    Sucic, Sonja; Dallinger, Stefan; Zdrazil, Barbara

    2010-01-01

    The serotonin transporter (SERT) terminates neurotransmission by removing serotonin from the synaptic cleft. In addition, it is the site of action of antidepressants (which block the transporter) and of amphetamines (which induce substrate efflux). We explored the functional importance of the N......(+) entry and accumulation of SERT(T81A) in the inward facing conformation ought to favor amphetamine-induced efflux. Thus, we surmised that the N terminus must play a direct role in driving the transporter into a state that supports amphetamine-induced efflux. This hypothesis was verified by truncating...

  6. Amphetamine poisoning in a dog: case report, literature review and veterinary medical perspectives.

    Science.gov (United States)

    Diniz, Pedro Paulo V P; Sousa, Marlos G; Gerardi, Daniel G; Tinucci-Costa, Mirela

    2003-12-01

    Amphetamine abuse in human beings has increased, resulting in many reports of toxicity and death. In the US over 4 million people have abused amphetamines at least once, thus small animals are exposed to increased accidental poisoning risk. This report describes an acute amphetamine poisoning in a dog due to ingestion of 15 mg/kg fenproporex, leading to typical signs of catecholamines release and effects in different organ systems. Similar clinical and laboratory findings observed in human beings are reviewed and physiopathogenic mechanisms discussed, as well as the therapeutic approaches available in veterinary medicine.

  7. Methamphetamine and amphetamine concentrations in postmortem rabbit tissues.

    Science.gov (United States)

    Nagata, T; Kimura, K; Hara, K; Kudo, K

    1990-11-01

    The feasibility of detecting methamphetamine and its major metabolite, amphetamine, in postmortem tissues over a 2-year period was examined. It is important to determine if the abuse and toxic effects of drugs can be proved from evidence found in decayed, submerged, or stained tissue materials. The blood, urine, liver, skeletal muscle, skin and extremity bones from rabbits given methamphetamine intravenously were kept at room temperature, under 4 different conditions: sealed in a test tube, dried in the open air, submerged in tap water and stained on gauze. Methamphetamine was present in all the samples, with slight change in concentration in case of sealed and air dried tissues. Changes varied in bones kept in water. There were considerable decreases in methamphetamine in blood and urine stains. Despite long term storage, drug abuse and/or toxicity could be determined, in all tissues examined.

  8. A single social defeat induces short-lasting behavioral sensitization to amphetamine

    NARCIS (Netherlands)

    de Jong, JG; Wasilewski, M; van der Vegt, BJ; Buwalda, B; Koolhaas, Jacob

    2005-01-01

    Repeated, intermittent exposure to psychostimulants or stressors results in long-lasting, progressive sensitization of the behavioral effects of a subsequent amphetamine (AMPH) challenge. Although behavioral sensitization has also been observed following a single drug pretreatment, the sensitizing

  9. In vivo amphetamine action is contingent on αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Mus, Liudmilla; Eisenrauch, Birgit

    2014-01-01

    Addiction to psychostimulants (ie, amphetamines and cocaine) imposes a major socioeconomic burden. Prevention and treatment represent unmet medical needs, which may be addressed, if the mechanisms underlying psychostimulant action are understood. Cocaine acts as a blocker at the transporters...

  10. One day of motor training with amphetamine impairs motor recovery following spinal cord injury.

    Science.gov (United States)

    Wong, Jamie K; Steward, Oswald

    2012-02-01

    It has previously been reported that a single dose of amphetamine paired with training on a beam walking task can enhance locomotor recovery following brain injury (Feeney et al., 1982). Here, we investigated whether this same drug/training regimen could enhance functional recovery following either thoracic (T9) or cervical (C5) spinal cord injury. Different groups of female Sprague-Dawley rats were trained on a beam walking task, and in a straight alley for assessment of hindlimb locomotor recovery using the BBB locomotor scale. For rats that received C5 hemisections, forelimb grip strength was assessed using a grip strength meter. Three separate experiments assessed the consequences of training rats on the beam walking task 24 h following a thoracic lateral hemisection with administration of either amphetamine or saline. Beginning 1 h following drug administration, rats either received additional testing/retraining on the beam hourly for 6 h, or they were returned to their home cages without further testing/retraining. Rats with thoracic spinal cord injuries that received amphetamine in conjunction with testing/retraining on the beam at 1 day post injury (DPI) exhibited significantly impaired recovery on the beam walking task and BBB. Rats with cervical spinal cord injuries that received training with amphetamine also exhibited significant impairments in beam walking and locomotion, as well as impairments in gripping and reaching abilities. Even when administered at 14 DPI, the drug/training regimen significantly impaired reaching ability in cervical spinal cord injured rats. Impairments were not seen in rats that received amphetamine without training. Histological analyses revealed that rats that received training with amphetamine had significantly larger lesions than saline controls. These data indicate that an amphetamine/training regimen that improves recovery after cortical injury has the opposite effect of impairing recovery following spinal cord injury

  11. Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues

    Science.gov (United States)

    Robinson, Mike J.F.; Anselme, Patrick; Suchomel, Kristen; Berridge, Kent C.

    2015-01-01

    Amphetamine and stress can sensitize mesolimbic dopamine-related systems. In Pavlovian autoshaping, repeated exposure to uncertainty of reward prediction can enhance motivated sign-tracking or attraction to a discrete reward-predicting cue (lever CS+), as well as produce cross-sensitization to amphetamine. However, it remains unknown how amphetamine-sensitization or repeated restraint stress interact with uncertainty in controlling CS+ incentive salience attribution reflected in sign-tracking. Here rats were tested in three successive phases. First, different groups underwent either induction of amphetamine sensitization or repeated restraint stress, or else were not sensitized or stressed as control groups (either saline injections only, or no stress or injection at all). All next received Pavlovian autoshaping training under either certainty conditions (100% CS-UCS association) or uncertainty conditions (50% CS-UCS association and uncertain reward magnitude). During training, rats were assessed for sign-tracking to the lever CS+ versus goal-tracking to the sucrose dish. Finally, all groups were tested for psychomotor sensitization of locomotion revealed by an amphetamine challenge. Our results confirm that reward uncertainty enhanced sign-tracking attraction toward the predictive CS+ lever, at the expense of goal-tracking. We also report that amphetamine sensitization promoted sign-tracking even in rats trained under CS-UCS certainty conditions, raising them to sign-tracking levels equivalent to the uncertainty group. Combining amphetamine sensitization and uncertainty conditions together did not add together to elevate sign-tracking further above the relatively high levels induced by either manipulation alone. In contrast, repeated restraint stress enhanced subsequent amphetamine-elicited locomotion, but did not enhance CS+ attraction. PMID:26076340

  12. Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues.

    Science.gov (United States)

    Robinson, Mike J F; Anselme, Patrick; Suchomel, Kristen; Berridge, Kent C

    2015-08-01

    Amphetamine and stress can sensitize mesolimbic dopamine-related systems. In Pavlovian autoshaping, repeated exposure to uncertainty of reward prediction can enhance motivated sign-tracking or attraction to a discrete reward-predicting cue (lever-conditioned stimulus; CS+), as well as produce cross-sensitization to amphetamine. However, it remains unknown how amphetamine sensitization or repeated restraint stress interact with uncertainty in controlling CS+ incentive salience attribution reflected in sign-tracking. Here rats were tested in 3 successive phases. First, different groups underwent either induction of amphetamine sensitization or repeated restraint stress, or else were not sensitized or stressed as control groups (either saline injections only, or no stress or injection at all). All next received Pavlovian autoshaping training under either certainty conditions (100% CS-UCS association) or uncertainty conditions (50% CS-UCS association and uncertain reward magnitude). During training, rats were assessed for sign-tracking to the CS+ lever versus goal-tracking to the sucrose dish. Finally, all groups were tested for psychomotor sensitization of locomotion revealed by an amphetamine challenge. Our results confirm that reward uncertainty enhanced sign-tracking attraction toward the predictive CS+ lever, at the expense of goal-tracking. We also reported that amphetamine sensitization promoted sign-tracking even in rats trained under CS-UCS certainty conditions, raising them to sign-tracking levels equivalent to the uncertainty group. Combining amphetamine sensitization and uncertainty conditions did not add together to elevate sign-tracking further above the relatively high levels induced by either manipulation alone. In contrast, repeated restraint stress enhanced subsequent amphetamine-elicited locomotion, but did not enhance CS+ attraction. (c) 2015 APA, all rights reserved).

  13. Caffeine induces differential cross tolerance to the amphetamine-like discriminative stimulus effects of dopaminergic agonists.

    Science.gov (United States)

    Jain, Raka; Holtzman, Stephen G

    2005-05-15

    The purpose of this study was to determine if caffeine induces cross tolerance to the amphetamine-like discriminative stimulus effects of dopaminergic drugs that act through distinct mechanisms (e.g., release, uptake inhibition, direct activation of dopamine D(1)- or D(2)-family receptors). Rats were trained to discriminate 1.0 mg/kg d-amphetamine from saline in a two-choice discrete-trial procedure. Stimulus-generalization curves were generated by cumulative dosing for d-amphetamine (0.1-1.0 mg/kg), methylphenidate (0.3-5.6 mg/kg), SKF 81297 (0.3-3.0 mg/kg), and R-(-)-propylnorapomorphine (NPA; 0.001-1.78 mg/kg), as well as for caffeine (3.0-56 mg/kg); curves were re-determined after twice daily injections of caffeine (30 mg/kg) for 3.5 days. The rats generalized dose dependently to the four dopaminergic drugs, but only to a limited extent to caffeine. Twice daily injections of caffeine induced significant cross tolerance (i.e., increased ED(50)) to the amphetamine-like discriminative effects of methylphenidate and SKF 81297, attenuated non-significantly the effects of NPA, and did not alter the effects of amphetamine. Thus, caffeine produces differential cross tolerance to the amphetamine-like discriminative effects of dopaminergic drugs, a phenomenon in which the dopamine D(1) receptor appears to have an important role.

  14. Individual behavioural predictors of amphetamine-induced emission of 50 kHz vocalization in rats.

    Science.gov (United States)

    Mulvihill, Kevin G; Brudzynski, Stefan M

    2018-05-11

    Measurement of ultrasonic vocalizations (USVs) produced by adult rats represents a highly useful index of emotional arousal. The associations found between 50 kHz USV production and a variety of behavioural and pharmacological protocols increasingly suggests they serve as a marker of positive motivational states. This study used a powerful within-subjects design to investigate the relationships among individual differences in approach to a sweet-food reward, predisposition to emit 50 kHz USVs spontaneously, and 50 kHz USVs emission following acute systemic administration of amphetamine. Both approach motivation and predisposition to call were found to not correlate with each other but did predict 50 kHz USV response to acute amphetamine. These two behavioural phenotypes appear to represent dissociable predictors of acute amphetamine-induced emission of 50 kHz USVs in a non-sensitization paradigm. In contrast to that, a measure of sucrose preference was not found to predict 50 kHz USV emission following amphetamine. Acute amphetamine was also found to increase average sound frequency of emitted USVs and selectively increase the proportion of Trill subtype 50 kHz USVs. Together, these data demonstrate that acute amphetamine-induced 50 kHz USVs in the adult rat represent more than just a univariate motivational state and may represent the product of dissociable subsystems of emotional behavior. Copyright © 2018. Published by Elsevier B.V.

  15. Development and evaluation of a radioimmunoassay for the detection of amphetamine and related compounds in biological fluids

    International Nuclear Information System (INIS)

    Mason, P.A.; Bal, T.S.; Law, B.; Moffat, A.C.

    1983-01-01

    A radioimmunoassay has been developed for the detection of amphetamine and its analogues in blood and urine without any pretreatment of the samples. It is based on a commercially available antiserum and a [ 125 I] iodinated derivative of amphetamine. The assay can detect low levels of amphetamine (less than 10 ng ml - 1 ) in very small samples (50 μl) of blood and urine. It is cheap (3 pence per test), rapid, simple to perform and is specific for compounds closely related to amphetamine. A high, positive correlation was obtained (r = 0.93) when results of the analyses of urine samples from volunteers who had ingested amphetamine were compared with those produced by gas chromatography - mass spectrometry. The assay has proved very useful for the detection of amphetamine and closely related compounds in biological fluids. (author)

  16. A rapid enhancement of locomotor sensitization to amphetamine by estradiol in female rats.

    Science.gov (United States)

    Zovkic, Iva B; McCormick, Cheryl M

    2017-11-14

    Estradiol moderates the effects of drugs of abuse in both humans and rodents. Estradiol's enhancement of behavioral effects resulting from high (>2.5mg/kg) doses of amphetamine is established in rats; there is less evidence for the role of estradiol in locomotor effects elicited by lower doses, which are less aversive, increase incentive motivation, involve different neural mechanisms than higher doses, and often more readily reveal group differences than do higher doses. Further, the extent to which estradiol is required for the induction versus the expression of sensitization is unknown. To establish a protocol, we replicated the effects of estradiol on locomotor sensitization to amphetamine reported in a previous study that involved a high locomotor-activating dose (1.5mg/kg) of amphetamine, but with a lower dose. Ovariectomized female rats received 5μg of estradiol benzoate (EB) or OIL 30min before each of 5 treatments of 1.0mg/kg amphetamine or saline; all received a 0.5mg/kg challenge dose three days later. Compared with results for OIL, EB enhanced the locomotor-activating effects of repeated 1.0mg/kg amphetamine across treatment days. In contrast, on challenge day, there was no difference between EB-saline and EB-amphetamine to the lower dose (i.e., no sensitization). Experiments 2 and 3 involved a shorter induction (2days) and a lengthier withdrawal (9days) before the challenge test for the expression of sensitization to better differentiate the induction phase from the expression phase. In Expt2, EB-, and not OIL-, treated rats showed sensitization to 0.5mg/kg amphetamine; neither group showed sensitization to 1.5mg/kg amphetamine (ceiling effect?). In Expt3, rats were treated with EB either in both the induction and expression phases, in one of the phases only, or in neither phase. There was an effect of hormone treatment on challenge day and not on induction day; rats given EB on Challenge day showed sensitization to 0.5mg/kg amphetamine; OIL rats did

  17. Maintaining class, producing gender: enhancement discourses about amphetamine in entertainment media.

    Science.gov (United States)

    McKenna, Stacey A

    2011-11-01

    Since the 1930s, amphetamine has been used for a variety of socially and medically condoned purposes including personal and performance enhancement. In the contemporary U.S., although amphetamine and its derivatives share a history, similar chemical composition, and physiological and psychiatric effects, they are typically treated and researched as two distinct groups: illegally produced methamphetamine and prescription amphetamine. This study is an examination of the social meanings of these categories and their users as represented in popular media. To complement existing research on drug discourses in popular news media, this study analysed entertainment media: ten novels, three seasons of Breaking Bad, six television episodes, and eight movies. Media were coded inductively and deductively using tenets of critical discourse analysis and rhetorical criticism. The author identified discourses about user subject positions and ideologies pertaining to enhancement-related motivations for use. Two important themes emerged from this analysis that construct amphetamine use and users in ways that reflect, legitimize and reproduce class and gender ideologies. First, discourses illustrate that distinct meanings of methamphetamine versus prescription amphetamine are linked to expectations about the respective socioeconomic class and social status of their users. Second, the discourses reflect gendered values and ideals about productivity and sexuality. In reality, American cultural and political-economic contexts may encourage the use of amphetamine to meet a variety of social expectations and economic needs. However, many policy and prevention efforts surrounding amphetamine use disproportionately target methamphetamine users and women. Because policy and prevention efforts can be influenced as much by social values as by data, it is important to examine the many arenas in which social values are produced and disseminated. Copyright © 2011 Elsevier B.V. All rights

  18. Amphetamine use and its associated factors in body builders: a study from Tehran, Iran.

    Science.gov (United States)

    Angoorani, Hooman; Narenjiha, Hooman; Tayyebi, Behnoosh; Ghassabian, Akhgar; Ahmadi, Gelareh; Assari, Shervin

    2012-05-09

    Epidemiological studies on all types of illicit drug use among athletes are essential for both the sport community and drug control achievements. Here, we investigated the prevalence and associated factors of amphetamine use in body builders in Tehran, Iran, 2007. This study is a secondary analysis of a substance use survey done in 103 randomly selected gymnasia in Tehran (capital city of Iran). The survey was conducted from November 2007 to January 2008 and included 843 randomly selected bodybuilders (aged 40 years or less). By interviews via questionnaires the following data were obtained: age, job, marital status, education level, housing status, average monthly family income, number of family members, gymnasium area (m(2)), number of trainers, number of gymnasium members, initiation time (months), weekly duration of the sporting activity (h), monthly cost of the sporting activity, purpose of participating in sporting activity, and history of anabolic steroid and amphetamine use. One hundred twenty (13.3%) body builders reported a history of amphetamine use. According to the results of regression analysis, being married (risk ratio - RR = 0.540), and participating in body building to enhance self-esteem (RR = 0.423) or to enhance sport performance (RR = 0.545) had protective effects on amphetamine use. However, having university qualifications (RR = 1.843), using anabolic steroids (RR = 1.803) and participating in sport to maintain fitness (RR = 2.472) were linked to increased risk of amphetamine use. Well-educated bodybuilders were more likely to use amphetamines, and why this is so needs to be discovered. If further studies show that they are not aware of the dangers associated with amphetamine use, providing them with information should be considered.

  19. Genetic variation of the ghrelin signalling system in individuals with amphetamine dependence.

    Science.gov (United States)

    Suchankova, Petra; Jerlhag, Elisabet; Jayaram-Lindström, Nitya; Nilsson, Staffan; Toren, Kjell; Rosengren, Annika; Engel, Jörgen A; Franck, Johan

    2013-01-01

    The development of amphetamine dependence largely depends on the effects of amphetamine in the brain reward systems. Ghrelin, an orexigenic peptide, activates the reward systems and is required for reward induced by alcohol, nicotine, cocaine and amphetamine in mice. Human genetic studies have shown that polymorphisms in the pre-proghrelin (GHRL) as well as GHS-R1A (GHSR) genes are associated with high alcohol consumption, increased weight and smoking in males. Since the heritability factor underlying drug dependence is shared between different drugs of abuse, we here examine the association between single nucleotide polymorphisms (SNPs) and haplotypes in the GHRL and GHSR, and amphetamine dependence. GHRL and GHSR SNPs were genotyped in Swedish amphetamine dependent individuals (n = 104) and controls from the general population (n = 310). A case-control analysis was performed and SNPs and haplotypes were additionally tested for association against Addiction Severity Interview (ASI) composite score of drug use. The minor G-allele of the GHSR SNP rs2948694, was more common among amphetamine dependent individuals when compared to controls (pc  = 0.02). A significant association between the GHRL SNP rs4684677 and ASI composite score of drug use was also reported (pc  = 0.03). The haplotype analysis did not add to the information given by the individual polymorphisms. Although genetic variability of the ghrelin signalling system is not a diagnostic marker for amphetamine dependence and problem severity of drug use, the present results strengthen the notion that ghrelin and its receptor may be involved in the development of addictive behaviours and may thus serve as suitable targets for new treatments of such disorders.

  20. Genetic variation of the ghrelin signalling system in individuals with amphetamine dependence.

    Directory of Open Access Journals (Sweden)

    Petra Suchankova

    Full Text Available The development of amphetamine dependence largely depends on the effects of amphetamine in the brain reward systems. Ghrelin, an orexigenic peptide, activates the reward systems and is required for reward induced by alcohol, nicotine, cocaine and amphetamine in mice. Human genetic studies have shown that polymorphisms in the pre-proghrelin (GHRL as well as GHS-R1A (GHSR genes are associated with high alcohol consumption, increased weight and smoking in males. Since the heritability factor underlying drug dependence is shared between different drugs of abuse, we here examine the association between single nucleotide polymorphisms (SNPs and haplotypes in the GHRL and GHSR, and amphetamine dependence. GHRL and GHSR SNPs were genotyped in Swedish amphetamine dependent individuals (n = 104 and controls from the general population (n = 310. A case-control analysis was performed and SNPs and haplotypes were additionally tested for association against Addiction Severity Interview (ASI composite score of drug use. The minor G-allele of the GHSR SNP rs2948694, was more common among amphetamine dependent individuals when compared to controls (pc  = 0.02. A significant association between the GHRL SNP rs4684677 and ASI composite score of drug use was also reported (pc  = 0.03. The haplotype analysis did not add to the information given by the individual polymorphisms. Although genetic variability of the ghrelin signalling system is not a diagnostic marker for amphetamine dependence and problem severity of drug use, the present results strengthen the notion that ghrelin and its receptor may be involved in the development of addictive behaviours and may thus serve as suitable targets for new treatments of such disorders.

  1. Post-training amphetamine administration enhances memory consolidation in appetitive Pavlovian conditioning: Implications for drug addiction.

    Science.gov (United States)

    Simon, Nicholas W; Setlow, Barry

    2006-11-01

    It has been suggested that some of the addictive potential of psychostimulant drugs of abuse such as amphetamine may result from their ability to enhance memory for drug-related experiences through actions on memory consolidation. This experiment examined whether amphetamine can specifically enhance consolidation of memory for a Pavlovian association between a neutral conditioned stimulus (CS-a light) and a rewarding unconditioned stimulus (US-food), as Pavlovian conditioning of this sort plays a major role in drug addiction. Male Long-Evans rats were given six training sessions consisting of 8 CS presentations followed by delivery of the food into a recessed food cup. After the 1st, 3rd, and 5th session, rats received subcutaneous injections of amphetamine (1.0 or 2.0 mg/kg) or saline vehicle immediately following training. Conditioned responding was assessed using the percentage of time rats spent in the food cup during the CS relative to a pre-CS baseline period. Both amphetamine-treated groups showed significantly more selective conditioned responding than saline controls. In a control experiment, there were no differences among groups given saline, 1.0 or 2.0 mg/kg amphetamine 2 h post-training, suggesting that immediate post-training amphetamine enhanced performance specifically through actions on memory consolidation rather than through non-mnemonic processes. This procedure modeled Pavlovian learning involved in drug addiction, in which the emotional valence of a drug reward is transferred to neutral drug-predictive stimuli such as drug paraphernalia. These data suggest that amphetamine may contribute to its addictive potential through actions specifically on memory consolidation.

  2. Amphetamine, clobenzorex, and 4-hydroxyclobenzorex levels following multidose administration of clobenzorex.

    Science.gov (United States)

    Cody, J T; Valtier, S

    2001-04-01

    Clobenzorex (Asenlix) is an anorectic drug used as part of a weight-management program. The drug is metabolized by the body to amphetamine, which is then excreted in the urine, thus causing difficulty in interpretation of amphetamine-positive drug tests. Previous studies have shown that the parent drug and several metabolites are excreted in urine. Clobenzorex itself has been detected for as long as 29 h following administration of a single dose. However, the parent drug was not always detected in samples that contained amphetamine at > or =500 ng/mL, the administrative cutoff for a positive result. Consequently, the parent compound clobenzorex is not ideal for ascertaining whether the drug was the origin of the amphetamine. Several metabolites of clobenzorex have been shown to be detected for a longer period of time than the parent. One of these, a hydroxy metabolite, was shown to be detected for an extended period of time. In a study of urine samples provided following administration of a single 30-mg dose of this drug, 4-hydroxyclobenzorex could be detected for up to 91.5 h. More significantly, that study showed all samples that were positive for amphetamine also contained detectable amounts of 4-hydroxyclobenzorex. This metabolite proved to be easily detected and was typically found at higher levels than amphetamine in urine samples positive for amphetamine long after clobenzorex itself could no longer be detected. The present study analyzed samples from a controlled multidose administration (30 mg of clobenzorex daily for seven days) for the presence of 4-hydroxyclobenzorex. The analytical procedure used acid hydrolysis followed by liquid-liquid extraction and gas chromatographic-mass spectrometric analysis with monitoring of ions at m/z 125, 330, and 364 for 4-hydroxyclobenzorex and its 3-Cl regioisomer, which was used as an internal standard. Peak concentrations of 4-hydroxyclobenzorex ranged from 17,786 to 99,044 ng/mL. Most importantly, this study also

  3. Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Mei-Fang [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Tzu Chi Center for Vascular Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Tzu Chi University of Science and Technology, Hualien, Taiwan (China); Lai, Su-Yu; Kung, Po-Cheng; Lin, Yo-Cheng [Department of Pharmacology and Toxicology, College of Medicine, Tzu Chi University, Hualien, Taiwan (China); Yang, Hui-I [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Chen, Po-Yi [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Department of Pharmacology and Toxicology, College of Medicine, Tzu Chi University, Hualien, Taiwan (China); Liu, Ingrid Y. [Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan (China); Lua, Ahai Chang [Department of Laboratory Medicine and Biotechnology & Graduate Institute of Medical Biotechnology, Tzu Chi University, Hualien, Taiwan (China); Lee, Tony Jer-Fu, E-mail: tlee@mail.tcu.edu.tw [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Tzu Chi Center for Vascular Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Department of Life Sciences, College of Life Sciences, Tzu Chi University, Hualien, Taiwan (China); Department of Pharmacology and Toxicology, College of Medicine, Tzu Chi University, Hualien, Taiwan (China); Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL (United States)

    2016-08-15

    The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O{sub 2} demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100 μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8 Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine > methamphetamine > hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic

  4. Neural activation to monetary reward is associated with amphetamine reward sensitivity.

    Science.gov (United States)

    Crane, Natania A; Gorka, Stephanie M; Weafer, Jessica; Langenecker, Scott A; de Wit, Harriet; Phan, K Luan

    2018-03-14

    One known risk factor for drug use and abuse is sensitivity to rewarding effects of drugs. It is not known whether this risk factor extends to sensitivity to non-drug rewards. In this study with healthy young adults, we examined the association between sensitivity to the subjective rewarding effects of amphetamine and a neural indicator of anticipation of monetary reward. We hypothesized that greater euphorigenic response to amphetamine would be associated with greater neural activation to anticipation of monetary reward (Win > Loss). Healthy participants (N = 61) completed four laboratory sessions in which they received d-amphetamine (20 mg) and placebo in alternating order, providing self-report measures of euphoria and stimulation at regular intervals. At a separate visit 1-3 weeks later, participants completed the guessing reward task (GRT) during fMRI in a drug-free state. Participants reporting greater euphoria after amphetamine also exhibited greater neural activation during monetary reward anticipation in mesolimbic reward regions, including the bilateral caudate and putamen. This is the first study to show a relationship between neural correlates of monetary reward and sensitivity to the subjective rewarding effects of amphetamine in humans. These findings support growing evidence that sensitivity to reward in general is a risk factor for drug use and abuse, and suggest that sensitivity of drug-induced euphoria may reflect a general sensitivity to rewards. This may be an index of vulnerability for drug use or abuse.

  5. Khat use and appetite: an overview and comparison of amphetamine, khat and cathinone.

    Science.gov (United States)

    Lemieux, Andrine M; Li, Bingshuo; al'Absi, Mustafa

    2015-02-03

    To understand the role of khat (Catha edulis) use on the aberrations in appetite and weight which are common comorbidities for khat and other amphetamine users. We provide a comprehensive overview and conceptual summary of the historical cultural use of khat as a natural stimulant and describe the similarities and differences between cathinone (the main psychoactive constituent of khat) and amphetamine highlighting the limited literature on the neurophysiology of appetite and subsequent weight effects of khat. Animal and some human studies indicate that khat produces appetite suppression, although little is known about mechanisms of this effect. Both direct and indirect effects of khat stem from multiple factors including behavioral, chemical and neurophysiological effects on appetite and metabolism. Classic and newly identified appetite hormones have not been explored sufficiently in the study of appetite and khat use. Unique methodological challenges and opportunities are encountered when examining effects of khat and cathinone including khat-specific medical comorbidities, unique route of administration, differential patterns of behavioral effects relative to amphetamines and the nascent state of our understanding of the neurobiology of this drug. A considerable amount of work remains in the study of the appetite effects of khat chewing and outline a program of research that could inform our understanding of this natural amphetamine׳s appetite effects and help prepare health care workers for the unique health effects of this drug. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Memory-related hippocampal functioning in ecstasy and amphetamine users: a prospective fMRI study.

    Science.gov (United States)

    Becker, Benjamin; Wagner, Daniel; Koester, Philip; Bender, Katja; Kabbasch, Christoph; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Jörg

    2013-02-01

    Recreational use of ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) has been associated with memory impairments. Functional neuroimaging studies with cross-sectional designs reported altered memory-related hippocampal functioning in ecstasy-polydrug users. However, differences might be pre-existing or related to the concomitant use of amphetamine. To prospectively investigate the specific effects of ecstasy on memory-related hippocampal functioning. We used an associative memory task and functional magnetic resonance imaging (fMRI) in 40 ecstasy and/or amphetamine users at baseline (t1) and after 12 months (t2). At t1, all subjects had very limited amphetamine and/or ecstasy experience (less than 5 units lifetime dose). Based on the reported drug use at t2, subjects with continued ecstasy and/or amphetamine use (n = 17) were compared to subjects who stopped use after t1 (n = 12). Analysis of repeated measures revealed that encoding-related activity in the left parahippocampal gyrus changed differentially between the groups. Activity in this region increased in abstinent subjects from t1 to t2, however, decreased in subjects with continued use. Decreases within the left parahippocampal gyrus were associated with the use of ecstasy, but not amphetamine, during the follow-up period. However, there were no significant differences in memory performance. The current findings suggest specific effects of ecstasy use on memory-related hippocampal functioning. However, alternative explanations such as (sub-)acute cannabis effects are conceivable.

  7. Verbal memory improved by D-amphetamine: influence of the testing effect.

    Science.gov (United States)

    Zeeuws, Inge; Deroost, Natacha; Soetens, Eric

    2010-07-01

    The improvement of long-term retention of verbal memory after an acute administration of D-amphetamine in recall and recognition tasks has been ascribed to an influence of the drug on memory consolidation. Because recent research has demonstrated that intermediate testing is of overriding importance for retention, we investigated whether D-amphetamine modulates the repeated testing effect in verbal long-term recognition. Forty men participated in two double blind placebo controlled studies. In Experiment 1, we manipulated the number of recognition tests and in Experiment 2, we compared repeated with nonrepeated testing of the same items. Drug effects were observed on delayed tests only, leaving immediate recognition unaffected. Number of intermediate recognition tests and repeated testing of the same items were not affected by D-amphetamine. We conclude that the D-amphetamine memory enhancement is not related to the testing effect. This result supports that D-amphetamine modulates other aspects of the consolidation process, probably related to context effects. (c) 2010 John Wiley & Sons, Ltd.

  8. Hollow-fiber liquid-phase microextraction of amphetamine-type stimulants in human hair samples.

    Science.gov (United States)

    do Nascimento Pantaleão, Lorena; Bismara Paranhos, Beatriz Aparecida Passos; Yonamine, Mauricio

    2012-09-07

    A fast method was optimized and validated in order to quantify amphetamine-type stimulants (amphetamine, AMP; methamphetamine, MAMP; fenproporex, FPX; 3,4-methylenedioxymethamphetamine, MDMA; and 3,4-methylenedioxyamphetamine, MDA) in human hair samples. The method was based in an initial procedure of decontamination of hair samples (50 mg) with dichloromethane, followed by alkaline hydrolysis and extraction of the amphetamines using hollow-fiber liquid-phase micro extraction (HF-LPME) in the three-phase mode. Gas chromatography-mass spectrometry (GC-MS) was used for identification and quantification of the analytes. The LoQs obtained for all amphetamines (around 0.05 ng/mg) were below the cut-off value (0.2 ng/mg) established by the Society of Hair Testing (SoHT). The method showed to be simple and precise. The intra-day and inter-day precisions were within 10.6% and 11.4%, respectively, with the use of only two deuterated internal standards (AMP-d5 and MDMA-d5). By using the weighted least squares linear regression (1/x²), the accuracy of the method was satisfied in the lower concentration levels (accuracy values better than 87%). Hair samples collected from six volunteers who reported regular use of amphetamines were submitted to the developed method. Drug detection was observed in all samples of the volunteers. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Amphetamine Self-Administration Attenuates Dopamine D2 Autoreceptor Function

    Science.gov (United States)

    Calipari, Erin S; Sun, Haiguo; Eldeeb, Khalil; Luessen, Deborah J; Feng, Xin; Howlett, Allyn C; Jones, Sara R; Chen, Rong

    2014-01-01

    Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors. Here, we reported that 5 days of amphetamine (AMPH) self-administration reduced the ability of D2 autoreceptors to inhibit DA release in the NAcc as determined by voltammetry. Using the antibody-capture [35S]GTPγS scintillation proximity assay, we demonstrated for the first time that midbrain D2/D3 receptors were preferentially coupled to Gαi2, whereas striatal D2/D3 receptors were coupled equally to Gαi2 and Gαo for signaling. Importantly, AMPH abolished the interaction between Gαi2 and D2/D3 receptors in the midbrain while leaving striatal D2/D3 receptors unchanged. The disruption of the coupling between D2/D3 receptors and Gαi2 by AMPH is at least partially explained by the enhanced RGS2 (regulator of G-protein signaling 2) activity resulting from an increased RGS2 trafficking to the membrane. AMPH had no effects on the midbrain expression and trafficking of other RGS proteins such as RGS4 and RGS8. Our data suggest that midbrain D2/D3 receptors are more susceptible to AMPH-induced alterations. Reduced D2 autoreceptor function could lead to enhanced DA signaling and ultimately addiction-related behavior. RGS2 may be a potential non-dopaminergic target for pharmacological intervention of dysfunctional DA transmission and drug addiction. PMID:24513972

  10. Hypoinsulinemia regulates amphetamine-induced reverse transport of dopamine.

    Directory of Open Access Journals (Sweden)

    Jason M Williams

    2007-10-01

    Full Text Available The behavioral effects of psychomotor stimulants such as amphetamine (AMPH arise from their ability to elicit increases in extracellular dopamine (DA. These AMPH-induced increases are achieved by DA transporter (DAT-mediated transmitter efflux. Recently, we have shown that AMPH self-administration is reduced in rats that have been depleted of insulin with the diabetogenic agent streptozotocin (STZ. In vitro studies suggest that hypoinsulinemia may regulate the actions of AMPH by inhibiting the insulin downstream effectors phosphotidylinositol 3-kinase (PI3K and protein kinase B (PKB, or Akt, which we have previously shown are able to fine-tune DAT cell-surface expression. Here, we demonstrate that striatal Akt function, as well as DAT cell-surface expression, are significantly reduced by STZ. In addition, our data show that the release of DA, determined by high-speed chronoamperometry (HSCA in the striatum, in response to AMPH, is severely impaired in these insulin-deficient rats. Importantly, selective inhibition of PI3K with LY294002 within the striatum results in a profound reduction in the subsequent potential for AMPH to evoke DA efflux. Consistent with our biochemical and in vivo electrochemical data, findings from functional magnetic resonance imaging experiments reveal that the ability of AMPH to elicit positive blood oxygen level-dependent signal changes in the striatum is significantly blunted in STZ-treated rats. Finally, local infusion of insulin into the striatum of STZ-treated animals significantly recovers the ability of AMPH to stimulate DA release as measured by high-speed chronoamperometry. The present studies establish that PI3K signaling regulates the neurochemical actions of AMPH-like psychomotor stimulants. These data suggest that insulin signaling pathways may represent a novel mechanism for regulating DA transmission, one which may be targeted for the treatment of AMPH abuse and potentially other dopaminergic disorders.

  11. Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals

    Science.gov (United States)

    Daberkow, DP; Brown, HD; Bunner, KD; Kraniotis, SA; Doellman, MA; Ragozzino, ME; Garris, PA; Roitman, MF

    2013-01-01

    Drugs of abuse hijack brain reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting non-exocytotic dopamine efflux via reverse transport. This mechanism of AMPH action, though, is inconsistent with its therapeutic effects and addictive properties - which are thought to be reliant on phasic dopamine signaling. Here we used fast-scan cyclic voltammetry in freely moving rats to interrogate principal neurochemical responses to AMPH in the striatum and relate these changes to behavior. First, we showed that AMPH dose-dependently enhanced evoked dopamine responses to phasic-like current pulse trains for up to two hours. Modeling the data revealed that AMPH inhibited dopamine uptake but also unexpectedly potentiated vesicular dopamine release. Second, we found that AMPH increased the amplitude, duration and frequency of spontaneous dopamine transients, the naturally occurring, non-electrically evoked, phasic increases in extracellular dopamine. Finally, using an operant sucrose reward paradigm, we showed that low-dose AMPH augmented dopamine transients elicited by sucrose-predictive cues. However, operant behavior failed at high-dose AMPH, which was due to phasic dopamine hyperactivity and the decoupling of dopamine transients from the reward predictive cue. These findings identify up-regulation of exocytotic dopamine release as a key AMPH action in behaving animals and support a unified mechanism of abused drugs to activate phasic dopamine signaling. PMID:23303926

  12. Determination of Amphetamine, Amfepramone and Fenproporex in Urine Samples by HPLC-DAD: Application to a Population of Brazilian Truck Drivers

    OpenAIRE

    Takitane, Juliana; Almeida, Rafael M.; Oliveira, Tiago F.; Prado, Natanael V.; Muñoz, Daniel R.; Leyton, Vilma; Yonamine, Mauricio

    2016-01-01

    Commercially available immunoassay tests are designed to detect the presence of amphetamine/methamphetamine or methylenodioxyamphetamines. However, it is known that Brazilian truck drivers also report the use of other illicit amphetamines, such as amfepramone and fenproporex. Thus, a method was developed and validated in order to quantify amphetamine-type stimulants (amphetamine, fenproporex and amfepramone) in urine by high performance liquid chromatography with diode array detection (HPLC-D...

  13. Effects of amphetamine on dopamine release in the rat nucleus accumbens shell region depend on cannabinoid CB1 receptor activation

    NARCIS (Netherlands)

    Kleijn, J.; Wiskerke, J.; Cremers, T.I.F.H.; Schoffelmeer, A.N.M.; Westerink, B.H.C.; Pattij, T.

    2012-01-01

    The psychostimulant drug amphetamine is often prescribed to treat Attention-Deficit/Hyperactivity Disorder. The behavioral effects of the psychostimulant drug amphetamine depend on its ability to increase monoamine neurotransmission in brain regions such as the nucleus accumbens (NAC) and medial

  14. Treatment of ADHD with amphetamine: short-term effects on family interaction.

    Science.gov (United States)

    Gustafsson, Peik; Hansson, Kjell; Eidevall, Lena; Thernlund, Gunilla; Svedin, Carl Göran

    2008-07-01

    This research seeks to study the impact on family function after 3 months of treatment with amphetamine. A total of 43 children, 6 to 11 years of age, with ADHD were treated with amphetamine for 3 months. Family function was studied before and after treatment by parent self-rating and independent observer ratings of videotaped parent-child interactions. The families with a child with ADHD were found to be more dysfunctional than control families. Families with children with severe ADHD behavior showed evidence of more family dysfunction compared to families with children with less severe ADHD behavior. After 3 months of treatment with amphetamine, the children's behavior and the mother's well-being and some aspects of parent-reported and observer-rated family functioning improved. This study gives support to the notion that some aspects of family dysfunction may be related to the child's ADHD behavior.

  15. Effects of d-Amphetamine and Haloperidol on Modulation of the Human Acoustic Startle Response

    Directory of Open Access Journals (Sweden)

    Hossein Kaviani

    2006-04-01

    Full Text Available "nObjective:This study aimed to examine the effects of haloperidol and amphetamine on human startle response modulated by emotionally-toned film clips. "n "n Method:Sixty participants, in two groups (one receiving haloperidol and the other receiving amphetamine were tested using electromyography (EMG to measure eye-blink muscle (orbicular oculi while different emotions were induced by six 2-minute film clips. Results:An affective rating shows the negative and positive effects of the two drugs on emotional reactivity, neither amphetamine nor haloperidol had any impact on the modulation of the startle response. Conclusion: The methodological and theoretical aspects of the study and findings will be discussed.

  16. A new screening method for amphetamine and methamphetamine using dansyl chloride derivatization and cartridge fluorescence.

    Science.gov (United States)

    Yamada, H; Ikeda-Wada, S; Oguri, K

    1998-07-01

    A new screening method for amphetamines was developed. It consists of derivatization with dansyl chloride, extraction of the derivative using a Sep-Pak C18 or a Bond Elut C18, solid phase extraction columns, and visualization of the fluorescence of the cartridge. A control test using drug-free urine showed no fluorescence. Amphetamine, methamphetamine and the methylenedioxy derivatives exhibited strong fluorescence, while related compounds, such as N-ethylamphetamine and fenetylline, were negative or weakly positive. The disadvantage of the present method is that it is a multi-step procedure and 20-30 min is required for screening. However, since it has a different specificity from the widely used immunochemical technique, it is suggested to be a useful screen for amphetamines.

  17. Cdk5 Is Essential for Amphetamine to Increase Dendritic Spine Density in Hippocampal Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Soledad Ferreras

    2017-11-01

    Full Text Available Psychostimulant drugs of abuse increase dendritic spine density in reward centers of the brain. However, little is known about their effects in the hippocampus, where activity-dependent changes in the density of dendritic spine are associated with learning and memory. Recent reports suggest that Cdk5 plays an important role in drug addiction, but its role in psychostimulant’s effects on dendritic spines in hippocampus remain unknown. We used in vivo and in vitro approaches to demonstrate that amphetamine increases dendritic spine density in pyramidal neurons of the hippocampus. Primary cultures and organotypic slice cultures were used for cellular, molecular, pharmacological and biochemical analyses of the role of Cdk5/p25 in amphetamine-induced dendritic spine formation. Amphetamine (two-injection protocol increased dendritic spine density in hippocampal neurons of thy1-green fluorescent protein (GFP mice, as well as in hippocampal cultured neurons and organotypic slice cultures. Either genetic or pharmacological inhibition of Cdk5 activity prevented the amphetamine–induced increase in dendritic spine density. Amphetamine also increased spine density in neurons overexpressing the strong Cdk5 activator p25. Finally, inhibition of calpain, the protease necessary for the conversion of p35 to p25, prevented amphetamine’s effect on dendritic spine density. We demonstrate, for the first time, that amphetamine increases the density of dendritic spine in hippocampal pyramidal neurons in vivo and in vitro. Moreover, we show that the Cdk5/p25 signaling and calpain activity are both necessary for the effect of amphetamine on dendritic spine density. The identification of molecular mechanisms underlying psychostimulant effects provides novel and promising therapeutic approaches for the treatment of drug addiction.

  18. Sweet taste liking is associated with subjective response to amphetamine in women but not men.

    Science.gov (United States)

    Weafer, Jessica; Lyon, Nicholas; Hedeker, Donald; de Wit, Harriet

    2017-11-01

    Preference for sweet taste rewards has been linked to the propensity for drug use in both animals and humans. Here, we tested the association between sweet taste liking and sensitivity to amphetamine reward in healthy adults. We hypothesized that sweet likers would report greater euphoria and stimulation following D-amphetamine (20 mg) compared to sweet dislikers. Men (n = 36) and women (n = 34) completed a sweet taste test in which they rated their liking of various concentrations of sucrose and filtered water (0.05, 0.10, 0.21, 0.42, and 0.83 M). Participants who preferred the highest concentration were classified as "sweet likers." All others were classified as "sweet dislikers." They then completed four sessions in which they received D-amphetamine (20 mg) and placebo in alternating order, providing self-report measures of euphoria and stimulation on the Addiction Research Center Inventory (ARCI) at regular intervals. We conducted linear mixed effects models to examine relationships between sweet liking and drug-induced euphoria and stimulation. Sweet likers reported significantly greater amphetamine-induced euphoria than did sweet dislikers among women. By contrast, sweet liking was not associated with amphetamine response in men. No associations with stimulation were observed. The association between sweet preference and amphetamine response in women is consistent with animal studies linking sweet taste preference and drug reward and also fits with observations that individuals who use drugs show a preference for sweet tastes. Whether the sex difference is related to circulating hormones, or other variables, remains to be determined.

  19. Amphetamine increases schedule-induced drinking reduced by negative punishment procedures.

    Science.gov (United States)

    Pérez-Padilla, Angeles; Pellón, Ricardo

    2003-05-01

    d-Amphetamine has been reported to increase schedule-induced drinking punished by lick-dependent signalled delays in food delivery. This might reflect a drug-behaviour interaction dependent on the type of punisher, because no such effect has been found when drinking was reduced by lick-contingent electric shocks. However, the anti-punishment effect of amphetamine could be mediated by other behavioural processes, such as a loss of discriminative control or an increase in the value of delayed reinforcers. To test the effects of d-amphetamine on the acquisition and maintenance of schedule-induced drinking reduced by unsignalled delays in food delivery. Rats received 10-s unsignalled delays initiated by each lick after polydipsia was induced by a fixed-time 30-s food reinforcement schedule or from the outset of the experiment. Yoked-control rats received these same delays but independently of their own behaviour. d-Amphetamine (0.1-3.0 mg/kg) was then tested IP. d-Amphetamine dose-dependently increased and then decreased punished schedule-induced drinking. The drug led to dose-dependent reductions when the delays were not contingent or when they were applied from the outset of training. These results support the contention that d-amphetamine has an increasing effect on schedule-induced drinking that has been previously reduced by a negative punishment procedure. This effect cannot be attributed to other potentially involved processes, and therefore support the idea that drug effects on punished behaviour depend on punishment being delays in food or shock deliveries.

  20. Amphetamine margin in sports. [Effects on performance of highly trained athletes

    Energy Technology Data Exchange (ETDEWEB)

    Laties, V.G.; Weiss, B.

    1980-01-01

    The amphetamines can enhance athletic performance. That much seems clear from the literature, some of which is reviewed here. Increases in endurance have been demonstrated in both man and rat. Smith and Beecher, 20 years ago, showed improvement of running, swimming, and weight throwing in highly trained athletes. Laboratory analogues of such performance have also been used and similar enhancement demonstrated. The amount of change induced by the amphetamines is usually small, of the order of a few percent. Nevertheless, since a fraction of a percent improvement can make the difference between fame and oblivion, the margin conferred by these drugs can be quite important.

  1. Acute but not delayed amphetamine treatment improves behavioral outcome in a rat embolic stroke model

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Overgaard, Karsten; Kristiansen, Uffe

    2011-01-01

    OBJECTIVES: The objective of this study was to examine the effects of d-amphetamine (amph) upon recovery after embolic stroke in rats. METHODS: Ninety-three rats were embolized in the right middle cerebral artery and assigned to: (1) controls; (2) combination (acute amph and later amph-facilitate...

  2. Cannabis and Amphetamine Use and Associated Factors among School-Going Adolescents in Nine African Countries

    Science.gov (United States)

    Peltzer, Karl; Pengpid, Supa

    2018-01-01

    The aim of this study was to assess the prevalence of cannabis and amphetamine use and associated factors among adolescents in nine African countries. We analyzed cross-sectional data from 25,372 adolescents (mean age 14.3 years, SD = 1.6) from nine African countries that participated in the Global School-Based Student Health Survey (GSHS) in…

  3. Cross-reactivity of amphetamine analogues with Roche Abuscreen radioimmunoassay reagents

    International Nuclear Information System (INIS)

    Cody, J.T.

    1990-01-01

    Cross-reactivity of amphetamine analogues with the Abuscreen amphetamine radioimmunoassay reagents was determined for both the standard and high specificity antibody systems. Compounds tested included 2-methoxyamphetamine, 4-hydroxymethamphetamine, 2,5-dimethoxyamphetamine (DMA), 4-bromo-2,5-dimethoxyamphetamine (DOB), 4-bromo-2,5-dimethoxy-beta-phenethylamine (BDMPEA), 3,4,5-trimethoxyamphetamine (TMA), 3,4-methylenedioxyamphetamine (MDA), N,N-dimethyl-3,4-methylenedioxyamphetamine and N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), 2,5-dimethoxy-4-ethylamphetamine, 2,5-dimethoxy-4-methylamphetamine (DOM), and 3,4,5-trimethoxyphenethylamine (mescaline). Blank negative reference material was spiked with 1,000 to 100,000 ng/mL of the amphetamine analogue and used as sample in the assays. MDA was the only analogue that showed cross reactivity equal to or greater than that of amphetamine. None of the other analogue compounds demonstrated a positive result at even the highest concentration; however several showed depressed counts at various concentration levels

  4. [Identification of Methamphetamine Abuse and Selegiline Use: Chiral Analysis of Methamphetamine and Amphetamine in Urine].

    Science.gov (United States)

    Xiang, P; Bu, J; Qiao, Z; Zhuo, X Y; Wu, H J; Shen, M

    2017-12-01

    To study the content variation of selegiline and its metabolites in urine, and based on actual cases, to explore the feasibility for the identification of methamphetamine abuse and selegiline use by chiral analysis. The urine samples were tested by chiral separation and LC-MS/MS method using CHIROBIOTIC™ V2 chiral liquid chromatography column. The chiral analysis of methamphetamine and amphetamine were performed on the urine samples from volunteers of selegiline use and drug addicts whom suspected taking selegiline. After 5 mg oral administration, the positive test time of selegiline in urine was less than 7 h. The mass concentrations of R(-)-methamphetamine and R(-)-amphetamine in urine peaked at 7 h which were 0.86 μg/mL and 0.18 μg/mL and couldn't be detected after 80 h and 168 h, respectively. The sources of methamphetamine and amphetamine in the urine from the drug addicts whom suspected taking selegiline were analysed successfully by present method. The chiral analysis of methamphetamine and amphetamine, and the determination of selegiline's metabolites can be used to distinguish methamphetamine abuse from selegiline use. Copyright© by the Editorial Department of Journal of Forensic Medicine

  5. Effects of OROS-MPH Versus Dl-Amphetamine-XR on Driving Performance of ADHD Adolescents

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-10-01

    Full Text Available Driving performance of 35 adolescent ADHD patients (19 boys/16 girls; mean age 17.8 years on a driving simulator was compared while taking OROS methylphenidate (Concerta, 72 mg, mixed dl-amphetamine salts (Adderall XR, 30 mg, or placebo in a randomized, double-blind, crossover study at University of Virginia, Charlottesville.

  6. Simulated Driving Changes in Young Adults with ADHD Receiving Mixed Amphetamine Salts Extended Release and Atomoxetine

    Science.gov (United States)

    Kay, Gary G.; Michaels, M. Alex; Pakull, Barton

    2009-01-01

    Background: Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder (ADHD). Method: This was a randomized, double-blind, placebo-controlled, crossover study of simulated driving performance with mixed amphetamine salts--extended release (MAS XR) 50 mg/day (Cohort 1) and…

  7. Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms.

    Science.gov (United States)

    Achterberg, E J Marijke; Trezza, Viviana; Siviy, Stephen M; Schrama, Laurens; Schoffelmeer, Anton N M; Vanderschuren, Louk J M J

    2014-04-01

    Social play behavior is a characteristic form of social behavior displayed by juvenile and adolescent mammals. This social play behavior is highly rewarding and of major importance for social and cognitive development. Social play is known to be modulated by neurotransmitter systems involved in reward and motivation. Interestingly, psychostimulant drugs, such as amphetamine and cocaine, profoundly suppress social play, but the neural mechanisms underlying these effects remain to be elucidated. In this study, we investigated the pharmacological underpinnings of amphetamine- and cocaine-induced suppression of social play behavior in rats. The play-suppressant effects of amphetamine were antagonized by the alpha-2 adrenoreceptor antagonist RX821002 but not by the dopamine receptor antagonist alpha-flupenthixol. Remarkably, the effects of cocaine on social play were not antagonized by alpha-2 noradrenergic, dopaminergic, or serotonergic receptor antagonists, administered either alone or in combination. The effects of a subeffective dose of cocaine were enhanced by a combination of subeffective doses of the serotonin reuptake inhibitor fluoxetine, the dopamine reuptake inhibitor GBR12909, and the noradrenaline reuptake inhibitor atomoxetine. Amphetamine, like methylphenidate, exerts its play-suppressant effect through alpha-2 noradrenergic receptors. On the other hand, cocaine reduces social play by simultaneous increases in dopamine, noradrenaline, and serotonin neurotransmission. In conclusion, psychostimulant drugs with different pharmacological profiles suppress social play behavior through distinct mechanisms. These data contribute to our understanding of the neural mechanisms of social behavior during an important developmental period, and of the deleterious effects of psychostimulant exposure thereon.

  8. Brain SPECT with /sup 123/I-isopropyl amphetamine in epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Reske, S.N.; Rasche, A.; Reichmann, K.; Winkler, C.; Froescher, W.; Kluenenberg, H.

    1983-04-01

    Ten patients were studied with N-isopropyl I-123 p-iodoamphetamine. Single photon emission computed tomography (SPECT) was carried out by hand of a rotating gamma camera system (Gammatome T9000/CGR, high resolution collimator). During 1 rotation (360/sup 0/) 64 frames (4k matrix) were acquired within 20 min 1 hour after injection of 6.5 mCi I-123 labeled amphetamine. The content of I-124 was less than 2%. After reconstruction of transverse slices coronar and sagittal reconstructions were rapidly performed using an array processor. Nine patients suffered from epilepsy and one from severe migraine. Excellent differentiation between gray and white matter of the cerebral cortex and the basal ganglia was evident in all of the cases. In 2 out of 3 patients with epilepsy and negative CT results SPECT revealed circumscribed areas with increased amphetamine uptake in accordance with the EEG findings. In 4 out of 6 cases with positive CT findings SPECT lesions with diminished amphetamine uptake could be established. One patient with severe migraine showed focal increased amphetamine uptake in accordance with the respective clinical results.

  9. Syntaxin 1A interaction with the dopamine transporter promotes amphetamine-induced dopamine efflux

    DEFF Research Database (Denmark)

    Binda, Francesca; Dipace, Concetta; Bowton, Erica

    2008-01-01

    of the dopamine (DA) transporter (DAT) as the site of direct interaction with SYN1A. Amphetamine (AMPH) increases the association of SYN1A with human DAT (hDAT) in a heterologous expression system (hDAT cells) and with native DAT in murine striatal synaptosomes. Immunoprecipitation of DAT from the biotinylated...

  10. Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle

    Science.gov (United States)

    Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

    Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning.

  11. Glucostatic regulation of (+)-[3H]amphetamine binding in the hypothalamus: correlation with Na+, K+-ATPase activity

    International Nuclear Information System (INIS)

    Angel, I.; Hauger, R.L.; Luu, M.D.; Giblin, B.; Skolnick, P.; Paul, S.M.

    1985-01-01

    Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (37 0 C) resulted in a time-dependent decrease in specific (+)-[ 3 H]amphetamine binding in the crude synaptosomal fraction prepared from these slices. The addition of D-glucose resulted in a dose- and time-dependent stimulation of (+)-[ 3 H]amphetamine binding, whereas incubations with L-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose failed to increase the number of (+)-[ 3 H]amphetamine binding sites. Ouabain potently inhibited the glucose-induced stimulation of (+)-[ 3 H]amphetamine binding, suggesting the involvement of Na + , K + -ATPase. Preincubation of hypothalamic slices with glucose also resulted in an increase in Na + ,K + -ATPase activity and the number of specific high-affinity binding sites for [ 3 H]ouabain, and a good correlation was observed between the glucose-stimulated increase in (+)-[ 3 H]amphetamine and [ 3 H]ouabain binding. These data suggest that the (+)-[ 3 H]amphetamine binding site in hypothalamus, previously linked to the anorectic actions of various phenylethylamines, is regulated both in vitro and in vivo by physiological concentrations of glucose. Glucose and amphetamine appear to interact at common sites in the hypothalamus to stimulate Na + ,K + -ATPase activity, and the latter may be involved in the glucostatic regulation of appetite

  12. [Persistent amphetamine consumption by truck drivers in São Paulo State, Brazil, despite the ban on production, prescription, and use].

    Science.gov (United States)

    Oliveira, Lúcio Garcia de; Endo, Ligia Goes; Sinagawa, Daniele Mayumi; Yonamine, Maurício; Munoz, Daniel Romero; Leyton, Vilma

    2013-09-01

    Amphetamine use by truck drivers for occupational purposes is widely known. The production and consumption of amphetamines was banned by the Brazilian National Health Surveillance Agency (ANVISA) in October 2011. This study analyzes persistent amphetamine use by truck drivers since the ban was implemented. A convenience sample of 427 truck drivers was taken along highways in São Paulo State in 2012. Participants were asked to answer a structured questionnaire and provide a urine sample to screen for recent amphetamine consumption through toxicological analysis. Among the interviewed drivers, 7% had used some illicit drug recently and 2.7% had used amphetamines. Amphetamines are still consumed by truck drivers despite the risks and the recent ban. The authorities should thus monitor the possession and use of amphetamines by drivers in order to effectively enforce the ban.

  13. Enhancement of a visual reinforcer by D-amphetamine and nicotine in adult rats: relation to habituation and food restriction.

    Science.gov (United States)

    Wright, Jennifer M; Ren, Suelynn; Constantin, Annie; Clarke, Paul B S

    2018-03-01

    Nicotine and D-amphetamine can strengthen reinforcing effects of unconditioned visual stimuli. We investigated whether these reinforcement-enhancing effects reflect a slowing of stimulus habituation and depend on food restriction. Adult male rats pressed an active lever to illuminate a cue light during daily 60-min sessions. Depending on the experiment, rats were challenged with fixed or varying doses of D-amphetamine (0.25-2 mg/kg IP) and nicotine (0.025-0.2 mg/kg SC) or with the tobacco constituent norharman (0.03-10 μg/kg IV). Experiment 1 tested for possible reinforcement-enhancing effects of D-amphetamine and norharman. Experiment 2 investigated whether nicotine and amphetamine inhibited the spontaneous within-session decline in lever pressing. Experiment 3 assessed the effects of food restriction. Amphetamine (0.25-1 mg/kg) and nicotine (0.1 mg/kg) increased active lever pressing specifically (two- to threefold increase). The highest doses of nicotine and amphetamine also affected inactive lever responding (increase and decrease, respectively). With the visual reinforcer omitted, responding was largely extinguished. Neither drug appeared to slow habituation, as assessed by the within-session decline in lever pressing, and reinforcement-enhancing effects still occurred if the drugs were given after this decline had occurred. Food restriction enhanced the reinforcement-enhancing effect of amphetamine but not that of nicotine. Responding remained goal-directed after several weeks of testing. Low doses of D-amphetamine and nicotine produced reinforcement enhancement even in free-feeding subjects, independent of the spontaneous within-session decline in responding. Reinforcement enhancement by amphetamine, but not nicotine, was enhanced by concurrent subchronic food restriction.

  14. Circulating adrenal hormones are not necessary for the development of sensitization to the psychomotor activating effects of amphetamine.

    Science.gov (United States)

    Badiani, A; Morano, M I; Akil, H; Robinson, T E

    1995-02-27

    We reported previously that when amphetamine is given in NOVEL test cages both its acute psychomotor activating effects (rotational behaviour and locomotor activity) and the degree of sensitization are greater than when amphetamine is given in HOME cages that are physically identical to the NOVEL test cages. Since exposure to the NOVEL environment increases plasma corticosterone levels (Experiment 1) it is possible that the enhancement in the effects of amphetamine in the NOVEL condition is mediated by corticosterone. If this hypothesis is correct adrenalectomy (ADX) should abolish the difference between the HOME and NOVEL groups. This was tested in three independent experiments, in which the response (rotational behavior in Experiments 2 and 3; locomotor activity and rearing behavior in Experiment 4) to repeated injections of amphetamine was assessed in rats that underwent adrenalectomy (ADX) or a sham operation (SHAM). ADX animals received either no corticosterone replacement or one of two corticosterone replacement treatments. Adrenalectomy, with or without corticosterone replacement treatment, had no significant effect on the development of amphetamine sensitization, either in the HOME or the NOVEL environment. By contrast, the effects of adrenalectomy on the acute response to amphetamine varied depending on the behavioral measure and possibly on the dose of amphetamine (2.0 mg/kg, 3.0 mg/kg and 1.5 mg/kg IP, in Experiments 2, 3 and 4, respectively). We conclude that: (i) a stress-induced secretion of adrenal hormones is not responsible for the enhancement in sensitization to amphetamine seen in animals tested in a NOVEL environment; (ii) circulating adrenal hormones are not necessary for development of sensitization to the psychomotor activating effects of amphetamine.

  15. Elucidating the sorption mechanism of “mixed-mode” SPME using the basic drug amphetamine as a model compound

    International Nuclear Information System (INIS)

    Peltenburg, Hester; Groothuis, Floris A.; Droge, Steven T.J.; Bosman, Ingrid J.; Hermens, Joop L.M.

    2013-01-01

    Graphical abstract: -- Highlights: •C18/propylsulfonic acid “mixed-mode” SPME fiber is efficient in sampling amphetamine. •Both protonated and neutral species of amphetamine sorb to the mixed-mode fiber. •Sorption of organic cations to this mixed-mode fiber depends on pH and salinity. •Amphetamine has a 20× higher affinity to the mixed-mode coating than to polyacrylate. -- Abstract: We studied the sorption of amphetamine as a model drug to represent small, polar organic cations to a new SPME coating combining C18 and propylsulfonic acid. This combination of hydrophobic and strong cation exchange (SCX) groups was compared to conventional SPME fibers with polyacrylate (PA) or C18 coating. The affinity of amphetamine at physiological pH (PBS) was 20 to 180 times greater for the new C18/SCX coating than for C18 alone and PA of different coating thickness. As amphetamine is a base and >99% protonated at physiological pH, this enhanced affinity is attributed to the ion-exchange phase in the coating. Tests at pH above the pK a of amphetamine show that, when normalized to the coating volume, neutral amphetamine also has a higher affinity compared to PA. As ion-exchange groups are not unlimitedly present in the coating, amphetamine isotherms level off to a saturation concentration on the C18/SCX fiber at the highest tested aqueous concentrations. Also, other cations (Na + , K + , Ca 2+ ) compete for the SCX sites and decrease the sorption coefficients, e.g. by 1.7 log units when comparing Milli-Q water with PBS. The C18/SCX fiber provides improved sensitivity over some of the classic SPME fibers. However, care should be taken near the cation exchange capacity of the fiber and the fiber should be calibrated in an appropriate matrix so as to eliminate competition effects

  16. Amphetamines, atomoxetine and the risk of serious cardiovascular events in adults.

    Directory of Open Access Journals (Sweden)

    Hedi Schelleman

    Full Text Available To compare the incidence rates of serious cardiovascular events in adult initiators of amphetamines or atomoxetine to rates in non-users.This was a retrospective cohort study of new amphetamines (n=38,586 or atomoxetine (n=20,995 users. Each medication user was matched to up to four non-users on age, gender, data source, and state (n=238,183. The following events were primary outcomes of interest 1 sudden death or ventricular arrhythmia, 2 stroke, 3 myocardial infarction, 4 a composite endpoint of stroke or myocardial infarction. Cox proportional hazard regression was used to calculate propensity-adjusted hazard ratios for amphetamines versus matched non-users and atomoxetine versus matched non-users, with intracluster dependence within matched sets accounted for using a robust sandwich estimator.The propensity-score adjusted hazard ratio for amphetamines use versus non-use was 1.18 (95% CI: 0.55-2.54 for sudden death/ventricular arrhythmia, 0.80 (95% CI: 0.44-1.47 for stroke, 0.75 (95% CI: 0.42-1.35 for myocardial infarction, and 0.78 (95% CI: 0.51-1.19 for stroke/myocardial infarction. The propensity-score adjusted hazard ratio for atomoxetine use versus non-use was 0.41 (95% CI: 0.10-1.75 for sudden death/ventricular arrhythmia, 1.30 (95% CI: 0.52-3.29 for stroke, 0.56 (95% CI: 0.16-2.00 for myocardial infarction, and 0.92 (95% CI: 0.44-1.92 for stroke/myocardial infarction.Initiation of amphetamines or atomoxetine was not associated with an elevated risk of serious cardiovascular events. However, some of the confidence intervals do not exclude modest elevated risks, e.g. for sudden death/ventricular arrhythmia.

  17. Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers

    Science.gov (United States)

    Mick, Inge; Myers, Jim; Ramos, Anna C; Stokes, Paul R A; Erritzoe, David; Colasanti, Alessandro; Gunn, Roger N; Rabiner, Eugenii A; Searle, Graham E; Waldman, Adam D; Parkin, Mark C; Brailsford, Alan D; Galduróz, José C F; Bowden-Jones, Henrietta; Clark, Luke; Nutt, David J; Lingford-Hughes, Anne R

    2016-01-01

    Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [11C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [11C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [11C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [11C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions. PMID:26552847

  18. Acute methoxetamine and amphetamine poisoning with fatal outcome: A case report

    Directory of Open Access Journals (Sweden)

    Marek Wiergowski

    2014-08-01

    Full Text Available Methoxetamine (MXE is a psychoactive substance distributed mostly via the Internet and is not liable to legal regulation in Poland. MXE has a toxicity profile similar to that of ketamine but longer-lasting effects. The paper describes a case of acute poisoning that resulted from recreational use of MXE and amphetamine and ended in death. In mid-July 2012, a 31-year old man was admitted to the clinical toxicology unit in Gdańsk because of poisoning with an unknown psychoactive substance. The patient was transported to the emergency department (ED at 5:15 a.m. in a very poor general condition, in a deep coma, with acute respiratory failure, hyperthermia (> 39°C and generalized seizures. Laboratory tests showed marked leukocytosis, signs of massive rhabdomyolysis, hepatic failure and beginning of acute renal failure. Despite intensive therapy, the patient died 4 weeks after the poisoning in the course of multi-organ dysfunction syndrome. Chemical and toxicological studies of serum and urine samples collected on the poisoning day at 1:40 p.m. confirmed that amphetamine and MXE had been taken earlier that day. Concentration of amphetamine in the serum (0.06 μg/ml was within the non-toxic range, while MXE (0.32 μg/ml was within the toxic range of concentrations. Amphetamine was also detected in the patient's hair, which suggested a possibility of its use within the last dozen weeks or so. The serious clinical course of intoxication and co-existence of amphetamine and MXE in the patient's blood and urine suggest the possibility of adverse interactions between them.

  19. Protective effects of amphetamine on gastric ulcerations induced by indomethacin in rats

    Institute of Scientific and Technical Information of China (English)

    Vlaicu Sandor; Barbu Cuparencu; Dan L Dumitrascu; Mircea A Birt; Tibor L Krausz

    2006-01-01

    AIM: To study the effects of amphetamine, an indirectacting adrenomimetic compound on the indomethacininduced gastric ulcerations in rats.METHODS: Male Wistar-Bratislava rats were randomly divided into four groups: Group 1 (control), received an ulcerogenic dose of indomethacin (50 μmol/kg) and Groups 2, 3 and 4, treated with amphetamine (10, 25and 50 μmol/kg). The drug was administered simultaneously with indomethacin and once again 4 h later.The animals were sacrificed 8 h after indomethacin treatment. The stomachs were opened and the incidence, the number of lesions and their severity were evaluated. The results were expressed as percentage and as mean ± standard error (mean ± SE).RESULTS: The incidence of ulceration in the control group was 100%. Amphetamine, at doses of 10, 25 and 50 μmol/kg, lowered the incidence to 88.89%, 77.78%and 37.5% respectively. The protection ratio was positive: 24.14%, 55.17% and 80.6% respectively. The total number of ulcerations/rat was 12.44 ± 3.69 in the control group. It decreased to 7.33 ± 1.89, 5.33 ± 2.38 and 2.25 ± 1.97 under the effects of the above-mentioned doses of amphetamine.CONCLUSION: Amphetamine affords a significant dose-dependent protection against the indomethacininduced gastric ulcerations in rats. It is suggested that the adrenergic system is involved in the gastric mucosa protection.

  20. Effects of prior amphetamine exposure on approach strategy in appetitive Pavlovian conditioning in rats.

    Science.gov (United States)

    Simon, Nicholas W; Mendez, Ian A; Setlow, Barry

    2009-03-01

    Pavlovian conditioning with a discrete reward-predictive visual cue can elicit two classes of behaviors: "sign-tracking" (approach toward and contact with the cue) and "goal-tracking" (approach toward the site of reward delivery). Sign-tracking has been proposed to be linked to behavioral disorders involving compulsive reward-seeking, such as addiction. Prior exposure to psychostimulant drugs of abuse can facilitate reward-seeking behaviors through enhancements in incentive salience attribution. Thus, it was predicted that a sensitizing regimen of amphetamine exposure would increase sign-tracking behavior. The purpose of these experiments was to determine how a regimen of exposure to amphetamine affects subsequent sign-tracking behavior. Male Long-Evans rats were given daily injections of d-amphetamine (2.0 mg/kg) or saline for 5 days, then given a 7-day drug-free period followed by testing in a Pavlovian conditioning task. In experiment 1, rats were presented with a visual cue (simultaneous illumination of a light and extension of a lever) located either to the left or right of a centrally located food trough. One cue (CS+) was always followed by food delivery, whereas the other (CS-) was not. In experiment 2, rats were tested in a nondiscriminative (CS+ only) version of the task. In both experiments, amphetamine-exposed rats showed less sign-tracking and more goal-tracking compared to saline controls. Contrary to predictions, prior amphetamine exposure decreased sign-tracking and increased goal-tracking behavior. However, these results do support the hypothesis that psychostimulant exposure and incentive sensitization enhance behavior directed toward reward-proximal cues at the expense of reward-distal cues.

  1. Risk factors of schizophrenia development in patients with amphetamines dependence and psychosis (amphetamine-induced psychosis and schizophrenia), and without psychosis [Czynniki ryzyka rozwoju schizofrenii u pacjentów uzależnionych od amfetaminy i jej pochodnych z psychozą (pointoksykacyjną lub schizofrenią) oraz bez psychozy

    OpenAIRE

    Rabe-Jabłońska, Jolanta; Mirek, Marta; Pawełczyk, Tomasz

    2012-01-01

    Aim. Amphetamine and its derivates can induce, usually after many intoxications, schizophrenia-like psychosis. These disorders appeared only in part patients with amphetamine dependence. Aim of the study was to establish prevalence of selective risk factors of schizophrenia development in amphetamine users: 1) with amphetamine – induced schizophrenia – like psychosis, 2) with schizophrenia, and 2) without psychotic symptoms. Material. In the study 3 groups of subjects were included: 30 amphet...

  2. Single Prazosin Infusion in Prelimbic Cortex Fosters Extinction of Amphetamine-Induced Conditioned Place Preference

    Directory of Open Access Journals (Sweden)

    Emanuele C. Latagliata

    2017-08-01

    Full Text Available Exposure to drug-associated cues to induce extinction is a useful strategy to contrast cue-induced drug seeking. Norepinephrine (NE transmission in medial prefrontal cortex has a role in the acquisition and extinction of conditioned place preference induced by amphetamine. We have reported recently that NE in prelimbic cortex delays extinction of amphetamine-induced conditioned place preference (CPP. A potential involvement of α1-adrenergic receptors in the extinction of appetitive conditioned response has been also suggested, although their role in prelimbic cortex has not been yet fully investigated. Here, we investigated the effects of the α1-adrenergic receptor antagonist prazosin infusion in the prelimbic cortex of C57BL/6J mice on expression and extinction of amphetamine-induced CPP. Acute prelimbic prazosin did not affect expression of amphetamine-induced CPP on the day of infusion, while in subsequent days it produced a clear-cut advance of extinction of preference for the compartment previously paired with amphetamine (Conditioned stimulus, CS. Moreover, prazosin-treated mice that had extinguished CS preference showed increased mRNA expression of brain-derived neurotrophic factor (BDNF and post-synaptic density 95 (PSD-95 in the nucleus accumbens shell or core, respectively, thus suggesting that prelimbic α1-adrenergic receptor blockade triggers neural adaptations in subcortical areas that could contribute to the extinction of cue-induced drug-seeking behavior. These results show that the pharmacological blockade of α1-adrenergic receptors in prelimbic cortex by a single infusion is able to induce extinction of amphetamine-induced CPP long before control (vehicle animals, an effect depending on contingent exposure to retrieval, since if infused far from or after reactivation it did not affect preference. Moreover, they suggest strongly that the behavioral effects depend on post-treatment neuroplasticity changes in corticolimbic

  3. The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Brandt-Christensen, M; Andersen, M B; Fink-Jensen, A

    2006-01-01

    -amphetamine-induced behaviours in EPS sensitised Cebus apella monkeys. (-)-OSU6162 was administered subcutaneously in doses of 1, 3, 6 and 9 mg/kg alone and in combination with (-)-apomorphine (0.25 mg/kg) or d-amphetamine (0.5 mg/kg). (-)-OSU6162 inhibited (-)-apomorphine-(1-9 mg/kg) as well as d-amphetamine (3-9 mg....../kg)-induced arousal and stereotypy. EPS did not occur when (-)-OSU6162 was administered in combination with (-)-apomorphine or d-amphetamine. However, when (-)-OSU6162 was administered alone, dystonia was observed at high doses (6 and 9 mg/kg) in two out of six monkeys. The present study shows that (-)-OSU6162 can...

  4. Association study of GABA system genes polymorphisms with amphetamine-induced psychotic disorder in a Han Chinese population.

    Science.gov (United States)

    Zhang, Kai; Zhao, Yan; Wang, Qingzhong; Jiang, Haifeng; Du, Jiang; Yu, Shunying; Zhao, Min

    2016-05-27

    GABA system genes have been implicated in neurotrophy and neurogenesis, which play pivotal roles in an individual's variation in vulnerability to amphetamine addiction or amphetamine-induced psychosis (AIP). We hypothesized that common genetic variants in the GABA system genes may be associated with amphetamine-induced psychotic disorder. In our study, thirty-six single nucleotide polymorphisms (SNPs) within the GABA system genes were genotyped in 400 amphetamine-induced psychotic disorder patients and 400 amphetamine use disorders patients (AUP) (not including those categorized as psychosis) in the Han Chinese population. In this study, 51.88% of the Han Chinese amphetamine-type substance use disorder patients met the criteria of amphetamine-induced psychotic disorder, and 79.5% amphetamine-induced psychotic disorder patients had auditory hallucinations, while 46.5% had delusions of reference. The allele frequency of rs1129647 showed nominal association with AIP in the Han Chinese population (P=0.03). Compared with AUP group patients, T allele frequency of AIP group patients was significantly increased. The adjustment for age and gender factors in the AIP and AUP patients was executed using unconditional logistic regression under five inheritance models. The genotype frequency of rs1129647 showed nominal association with AIP in the log-additive model (P=0.04). The genotype frequency of rs2290733 showed nominal association with AIP in the recessive model (P=0.04). Compared with female AIP patients, male patients were more likely to have the CC genotype of rs17545383 (P=0.04). Moreover, we determined that more male patients carried the T allele of rs2290733 in the AIP group (P=0.004). Unfortunately, the significant differences did not survive Benjamini-Hochberg false discovery rate correction (adjusted P>0.05). No association between the SNPs of the GABA system genes and amphetamine-induced psychotic disorder risk was identified. No haplotype of the GABA system

  5. Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys

    OpenAIRE

    Banks, Matthew L.; Smith, Douglas A.; Kisor, David F.; Poklis, Justin L.

    2015-01-01

    Methamphetamine is a globally abused drug that is metabolized to amphetamine, which also produces abuse-related behavioral effects. However, the contributing role of methamphetamine metabolism to amphetamine in methamphetamine's abuse-related subjective effects is unknown. This preclinical study was designed to determine 1) the relationship between plasma methamphetamine levels and methamphetamine discriminative stimulus effects and 2) the contribution of the methamphetamine metabolite amphet...

  6. Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice

    DEFF Research Database (Denmark)

    Schmidt, Lene S; Miller, Anthony D; Lester, Deranda B

    2010-01-01

    showed that M(5) receptor knockout (M (5) (-/-) ) mice are less sensitive to the reinforcing properties of addictive drugs. MATERIALS AND METHODS: Here, we investigate the role of M(5) receptors in the effects of amphetamine and cocaine on locomotor activity, locomotor sensitization, and dopamine release......-induced hyperactivity and dopamine release as well as amphetamine sensitization are enhanced in mice lacking the M(5) receptor. These results support the concept that the M(5) receptor modulates effects of addictive drugs....

  7. Breakingtheice: a protocol for a randomised controlled trial of an internet-based intervention addressing amphetamine-type stimulant use.

    Science.gov (United States)

    Tait, Robert J; McKetin, Rebecca; Kay-Lambkin, Frances; Bennett, Kylie; Tam, Ada; Bennett, Anthony; Geddes, Jenny; Garrick, Adam; Christensen, Helen; Griffiths, Kathleen M

    2012-06-25

    The prevalence of amphetamine-type stimulant use is greater than that of opioids and cocaine combined. Currently, there are no approved pharmacotherapy treatments for amphetamine-type stimulant problems, but some face-to-face psychotherapies are of demonstrated effectiveness. However, most treatment services focus on alcohol or opioid disorders, have limited reach and may not appeal to users of amphetamine-type stimulants. Internet interventions have proven to be effective for some substance use problems but none has specifically targeted users of amphetamine-type stimulants. The study will use a randomized controlled trial design to evaluate the effect of an internet intervention for amphetamine-type stimulant problems compared with a waitlist control group. The primary outcome will be assessed as amphetamine-type stimulant use (baseline, 3 and 6 months). Other outcomes measures will include 'readiness to change', quality of life, psychological distress (K-10 score), days out of role, poly-drug use, help-seeking intention and help-seeking behavior. The intervention consists of three modules requiring an estimated total completion time of 90 minutes. The content of the modules was adapted from face-to-face clinical techniques based on cognitive behavior therapy and motivation enhancement. The target sample is 160 men and women aged 18 and over who have used amphetamine-type stimulants in the last 3 months. To our knowledge this will be the first randomized controlled trial of an internet intervention specifically developed for users of amphetamine-type stimulants. If successful, the intervention will offer greater reach than conventional therapies and may engage clients who do not generally seek treatment from existing service providers. Australian and New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) ACTRN12611000947909.

  8. Breakingtheice: A protocol for a randomised controlled trial of an internet-based intervention addressing amphetamine-type stimulant use

    Directory of Open Access Journals (Sweden)

    Tait Robert J

    2012-06-01

    Full Text Available Abstract Background The prevalence of amphetamine-type stimulant use is greater than that of opioids and cocaine combined. Currently, there are no approved pharmacotherapy treatments for amphetamine-type stimulant problems, but some face-to-face psychotherapies are of demonstrated effectiveness. However, most treatment services focus on alcohol or opioid disorders, have limited reach and may not appeal to users of amphetamine-type stimulants. Internet interventions have proven to be effective for some substance use problems but none has specifically targeted users of amphetamine-type stimulants. Design/method The study will use a randomized controlled trial design to evaluate the effect of an internet intervention for amphetamine-type stimulant problems compared with a waitlist control group. The primary outcome will be assessed as amphetamine-type stimulant use (baseline, 3 and 6 months. Other outcomes measures will include ‘readiness to change’, quality of life, psychological distress (K-10 score, days out of role, poly-drug use, help-seeking intention and help-seeking behavior. The intervention consists of three modules requiring an estimated total completion time of 90 minutes. The content of the modules was adapted from face-to-face clinical techniques based on cognitive behavior therapy and motivation enhancement. The target sample is 160 men and women aged 18 and over who have used amphetamine-type stimulants in the last 3 months. Discussion To our knowledge this will be the first randomized controlled trial of an internet intervention specifically developed for users of amphetamine-type stimulants. If successful, the intervention will offer greater reach than conventional therapies and may engage clients who do not generally seek treatment from existing service providers. Trial registration Australian and New Zealand Clinical Trials Registry (http://www.anzctr.org.au/ ACTRN12611000947909

  9. Brain abnormalities detected on magnetic resonance imaging of amphetamine users presenting to an emergency department: a pilot study.

    Science.gov (United States)

    Fatovich, Daniel M; McCoubrie, David L; Song, Swithin J; Rosen, David M; Lawn, Nick D; Daly, Frank F

    2010-09-06

    To determine the prevalence of occult brain abnormalities in magnetic resonance imaging of active amphetamine users. Prospective convenience study in a tertiary hospital emergency department (ED). Patients presenting to the ED for an amphetamine-related reason were eligible for inclusion. We collected demographic data, drug use data, and performed a mini-mental state examination (MMSE). The proportion of patients with an abnormality on their MRI scan. Of 38 patients enrolled, 30 had MRI scans. Nineteen were male and their mean age was 26.7 +/- 5.4 years (range 19-41 years). The mean age of first amphetamine use was 18 years (range 13-26 years). Sixteen patients used crystal methamphetamine (mean amount 2.5 g/week), nine used amphetamine ("speed") (mean amount 2.9 g/week), and 23 used ecstasy (mean amount 2.3 tablets/week). Marijuana was smoked by 26 (mean amount 5.9 g/week), and 28 drank alcohol (mean amount 207 g/week). The median MMSE score was 27/30 (interquartile range, 26-29). Abnormalities on brain MRI scans were identified in six patients, most commonly an unidentified bright object (n = 4). In this pilot study of brain MRI of young people attending the ED with an amphetamine-related presentation, one in five had an occult brain lesion. While the significance of this is uncertain, it is congruent with evidence that amphetamines cause brain injury.

  10. Dopamine-independent locomotor actions of amphetamines in a novel acute mouse model of Parkinson disease.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available Brain dopamine is critically involved in movement control, and its deficiency is the primary cause of motor symptoms in Parkinson disease. Here we report development of an animal model of acute severe dopamine deficiency by using mice lacking the dopamine transporter. In the absence of transporter-mediated recycling mechanisms, dopamine levels become entirely dependent on de novo synthesis. Acute pharmacological inhibition of dopamine synthesis in these mice induces transient elimination of striatal dopamine accompanied by the development of a striking behavioral phenotype manifested as severe akinesia, rigidity, tremor, and ptosis. This phenotype can be reversed by administration of the dopamine precursor, L-DOPA, or by nonselective dopamine agonists. Surprisingly, several amphetamine derivatives were also effective in reversing these behavioral abnormalities in a dopamine-independent manner. Identification of dopamine transporter- and dopamine-independent locomotor actions of amphetamines suggests a novel paradigm in the search for prospective anti-Parkinsonian drugs.

  11. Acute myocardial infarction with multiple coronary thromboses in a young addict of amphetamines and benzodiazepines

    Directory of Open Access Journals (Sweden)

    Mohammed A. Al Shehri

    2016-07-01

    Full Text Available A 35-year-old man of average build and a smoker, with a background of a psychiatric disorder, was brought by his neighbor to the emergency department after an hour of severe chest pain. Upon arrival at the hospital he had cardiac arrest, was resuscitated, and moved to the catheterization laboratory with inferior, posterior, and lateral myocardial infarction. Coronary angiography showed an unusual thrombosis in multiple coronary branches. Toxicology report showed high levels of amphetamines and benzodiazepines in the patient’s original blood sample. The patient was kept under ventilation for 18 days, with difficult recovery due to severe withdrawal manifestations, ventilation acquired pneumonia, and rhabdomyolysis inducing acute renal failure. The patient regained near normal left ventricular function after baseline severe regional and global dysfunction. We postulate a relationship between the use of amphetamines, potentiated by benzodiazepines, and occurrence of acute thrombosis of multiple major coronary arteries.

  12. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Science.gov (United States)

    Parnaudeau, Sébastien; Dongelmans, Marie-louise; Turiault, Marc; Ambroggi, Frédéric; Delbes, Anne-Sophie; Cansell, Céline; Luquet, Serge; Piazza, Pier-Vincenzo; Tronche, François; Barik, Jacques

    2014-01-01

    The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs) release. GCs bind the glucocorticoid receptor (GR) a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While GR within dopamine-innervated areas drives cocaine's behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurons is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice. PMID:24574986

  13. Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

    Science.gov (United States)

    Lee Stubbeman, Bobbie; Brown, Clifford J; Yates, Justin R; Bardgett, Mark E

    2017-10-05

    Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Interactions between estradiol and haloperidol on perseveration and reversal learning in amphetamine-sensitized female rats.

    Science.gov (United States)

    Almey, Anne; Arena, Lauren; Oliel, Joshua; Shams, Waqqas M; Hafez, Nada; Mancinelli, Cynthia; Henning, Lukas; Tsanev, Aleks; Brake, Wayne G

    2017-03-01

    There are sex differences associated with schizophrenia, as women exhibit later onset of the disorder, less severe symptomatology, and better response to antipsychotic medications. Estrogens are thought to play a role in these sex differences; estrogens facilitate the effects of antipsychotic medications to reduce the positive symptoms of schizophrenia, but it remains unclear whether estrogens protect against the cognitive symptoms of this disorder. Amphetamine sensitization is used to model some symptoms of schizophrenia in rats, including cognitive deficits like excessive perseveration and slower reversal learning. In this experiment female rats were administered a sensitizing regimen of amphetamine to mimic these cognitive symptoms. They were ovariectomized and administered either low or high estradiol replacement as well as chronic administration of the antipsychotic haloperidol, and were assessed in tests of perseveration and reversal learning. Results of these experiments demonstrated that, in amphetamine-sensitized rats, estradiol alone does not affect perseveration or reversal learning. However, low estradiol facilitates a 0.25mg/day dose of haloperidol to reduce perseveration and improve reversal learning. Combined high estradiol and 0.25mg/day haloperidol has no effect on perseveration or reversal learning, but high estradiol facilitates the effects of 0.13mg/day haloperidol to reduce perseveration and improve reversal learning. Thus, in amphetamine-sensitized female rats, 0.25mg/day haloperidol only improved perseveration and reversal learning when estradiol was low, while 0.13mg/day haloperidol only improved these cognitive processes when estradiol was high. These findings suggest that estradiol facilitates the effects of haloperidol to improve perseveration and reversal learning in a dose-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Directory of Open Access Journals (Sweden)

    Sebastien eParnaudeau

    2014-02-01

    Full Text Available The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs release. GCs bind the glucocorticoid receptor (GR a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While the GR within dopamine-innervated areas drives cocaine’s behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurones is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice.

  16. Membrane permeable C-terminal dopamine transporter peptides attenuate amphetamine-evoked dopamine release

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Owens, WA; Winkler, Marie-Therese

    2013-01-01

    The dopamine transporter (DAT) is responsible for sequestration of extracellular dopamine (DA). The psychostimulant amphetamine (AMPH) is a DAT substrate, which is actively transported into the nerve terminal, eliciting vesicular depletion and reversal of DA transport via DAT. Here, we investigate......-terminal protein-protein interactions are critical for AMPH-evoked DA efflux and suggest that it may be possible to target protein-protein interactions to modulate transporter function and interfere with psychostimulant effects....

  17. Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD.

    Science.gov (United States)

    Cherkasova, Mariya V; Faridi, Nazlie; Casey, Kevin F; O'Driscoll, Gillian A; Hechtman, Lily; Joober, Ridha; Baker, Glen B; Palmer, Jennifer; Dagher, Alain; Leyton, Marco; Benkelfat, Chawki

    2014-05-01

    Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [(11)C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87 ± 8.65) and 18 healthy male controls (age: 25.44 ± 6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [(11)C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [(11)C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.

  18. Amphetamine sensitization alters reward processing in the human striatum and amygdala.

    Directory of Open Access Journals (Sweden)

    Owen G O'Daly

    Full Text Available Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.

  19. Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine.

    Science.gov (United States)

    Dos Santos, Rafael G; Valle, Marta; Bouso, José Carlos; Nomdedéu, Josep F; Rodríguez-Espinosa, José; McIlhenny, Ethan H; Barker, Steven A; Barbanoj, Manel J; Riba, Jordi

    2011-12-01

    Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting β-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users.

  20. A triazolam/amphetamine dose-effect interaction study: dissociation of effects on memory versus arousal.

    Science.gov (United States)

    Mintzer, Miriam Z; Griffiths, Roland R

    2007-06-01

    In addition to producing robust memory impairment, benzodiazepines also induce marked sedation. Thus, it is possible that the observed amnestic effects are secondary to more global sedative effects and do not reflect a specific primary benzodiazepine effect on memory mechanisms. The objective was to use the nonspecific stimulant d-amphetamine to dissociate the sedative and memory-impairing effects of the benzodiazepine triazolam. Single oral doses of placebo, triazolam alone (0.25, 0.50 mg/70 kg), d-amphetamine sulfate alone (20, 30 mg/70 kg), and triazolam (0.25, 0.50 mg/70 kg) and d-amphetamine sulfate (20, 30 mg/70 kg) conjointly (at all dose combinations) were administered to 18 healthy adult participants across nine sessions in a double-blind, staggered-dosing, crossover design. In addition to standard data analyses, analyses were also conducted on z-score standardized data, enabling effects to be directly compared across measures. Relative to the sedative measures, the memory measures generally exhibited a pattern of less reversal of triazolam's effects by d-amphetamine. The memory measures ranged in degree of reversal such that the most reversal was observed for reaction time on the n-back working memory task, and the least reversal was observed for accuracy on the Sternberg working memory task, with most measures showing an overall pattern of partial reversal. Benzodiazepines have specific effects on memory that are not merely a by-product of the drugs' sedative effects, and the degree to which sedative effects contribute to the amnestic effects varies as a function of the particular memory process being assessed.

  1. Clinical characteristics and outcome of heart failure and captagon amphetamine use: An observational prospective study

    OpenAIRE

    Abdelfatah A. Elasfar; Kamal Eldein Ahmad; Waleed AlShaghaa

    2014-01-01

    The fenetylline (captagon) tablets (an amphetamine like substance) are a stimulant drugs which are widely used in the Arabian Peninsula. Objectives: The aim of this study was to evaluate the clinical characteristics and outcome of acute heart failure in patients using captagon tablets. Methods: From September, 2009, through December, 2011, 280 consecutive patients with acute dilated cardiomyopathy and acute heart failure syndrome presented to emergency department in one tertiary care ce...

  2. Profile of Executive and Memory Function Associated with Amphetamine and Opiate Dependence

    Science.gov (United States)

    Ersche, Karen D; Clark, Luke; London, Mervyn; Robbins, Trevor W; Sahakian, Barbara J

    2007-01-01

    Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetamine-dependent individuals, opiate-dependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants were administered the Tower of London (TOL) planning task and the 3D-IDED attentional set-shifting task to assess executive function, and Paired Associates Learning and Delayed Pattern Recognition Memory tasks to assess visual memory function. The three groups of substance users showed significant impairments on TOL planning, Pattern Recognition Memory and Paired Associates Learning. Current amphetamine users displayed a greater degree of impairment than current opiate users. Consistent with previous research showing that healthy men are performing better on visuo-spatial tests than women, our male controls remembered significantly more paired associates than their female counterparts. This relationship was reversed in drug users. While performance of female drug users was normal, male drug users showed significant impairment compared to both their female counterparts and male controls. There was no difference in performance between current and former drug users. Neither years of drug abuse nor years of drug abstinence were associated with performance. Chronic drug users display pronounced neuropsychological impairment in the domains of executive and memory function. Impairment persists after several years of drug abstinence and may reflect neuropathology in frontal and temporal cortices. PMID:16160707

  3. The modulation effects of d-amphetamine and procaine on the spontaneously generated action potentials in the central neuron of snail, Achatina fulica Ferussac.

    Science.gov (United States)

    Lin, Chia-Hsien; Tsai, Ming-Cheng

    2005-05-01

    The modulation effects of d-amphetamine and procaine on the spontaneously generated action potentials were studied on the RP1 central neuron of giant African snails (Achatina fulica Ferussac). Extra-cellular application of d-amphetamine or procaine reversibly elicited bursts of potential (BoP). Prazosin, propranolol, atropine or d-tubocurarine did not alter the BoP elicited by either d-amphetamine or procaine. KT-5720 or H89 (protein kinase A inhibitors) blocked d-amphetamine-elicited BoP, whereas they did not block the procaine-elicited BoP. U73122, neomycin (phospholipase C inhibitors) blocked the procaine-elicited BoP, whereas they did not block the d-amphetamine-elicited BoP in the same neuron. These results suggest that BoP elicited by d-amphetamine or procaine were associated with protein kinase A and phospholipase C activity in the neuron.

  4. The effects of diazepam and zolpidem on cocaine- and amphetamine-induced place preference.

    Science.gov (United States)

    Meririnne, E; Kankaanpää, A; Lillsunde, P; Seppälä, T

    1999-01-01

    Drugs such as benzodiazepines, which enhance the effects of inhibitory neurotransmitter gamma-amino butyric acid (GABA), are known to modulate the mesocorticolimbic dopaminergic system, which is considered to mediate the rewarding effects of psychostimulants. The effects of diazepam, a benzodiazepine that binds unspecifically to omega 1- (omega1-) and omega2-receptors, and zolpidem, a nonbenzodiazepine drug that binds preferentially to omega1-receptors, on cocaine- and amphetamine-induced place preference were evaluated in Wistar rats. In tests using the counterbalanced method, neither diazepam (0.2, 1, and 5 mg/kg) nor zolpidem (2.5, 5, and 10 mg/kg) alone induced place preference or place aversion. Diazepam pretreatment prevented both cocaine- and amphetamine-induced (15 and 9 mg/kg, respectively) place preference; however, at doses that were earlier shown to cause sedation and amnesia, zolpidem failed to prevent either cocaine- or amphetamine-induced place preference. These results suggest that diazepam interferes with the rewarding properties of the psychostimulants, whereas zolpidem is less effective in this respect, possibly due to differential distribution of omega1- and omega2-receptors in the brain.

  5. Predictors of Hazardous Alcohol Consumption Among Young Adult Amphetamine-Type Stimulant Users

    Directory of Open Access Journals (Sweden)

    Ellen M. Leslie

    2016-02-01

    Full Text Available Background: Very high levels of alcohol consumption have been observed in young adult amphetamine-type stimulant (i.e., ecstasy and methamphetamine users. The reasons for this association are poorly understood. Objective: To examine predictors of hazardous alcohol consumption in a sample of young adult amphetamine-type stimulant users after 30 months of follow-up, controlling for potential confounders. Method: Analysis of longitudinal data from a population-derived sample of Australian young adult amphetamine-type stimulant users (n = 292. A prediction model of alcohol use at 30 months was developed using generalized linear latent and mixed modeling (GLLAMM. Results: Concurrently using ecstasy (Adjusted Odds Ratio [AOR] = 2.67, 95% Confidence Interval [CI] = [1.41, 5.07], frequently attending nightclubs (AOR = 2.53, 95% CI = [1.04, 6.16], high baseline alcohol use patterns (AOR = 2.06, 95% CI = [1.32, 3.20], and being male (AOR = 3.60, 95% CI = [1.48, 8.78] were associated with an increased likelihood of hazardous alcohol use at 30 months. Conclusion: Concurrent, but not baseline, ecstasy use was associated with hazardous alcohol use, suggesting that combined use of these substances may have an instrumental role in terms of the social functions of drug use (e.g., increasing capacity to drink. Integration of educational interventions concerning alcohol and stimulants is warranted.

  6. Neurotoxicity of amphetamine derivatives is mediated by caspase pathway activation in rat cerebellar granule cells

    International Nuclear Information System (INIS)

    Jimenez, Andres; Jorda, Elvira G.; Verdaguer, Ester; Pubill, David; Sureda, Francesc X.; Canudas, Anna M.; Escubedo, Elena; Camarasa, Jordi; Camins, Antoni; Pallas, Merce

    2004-01-01

    The neurotoxic action of the abuse drugs methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) on cerebellar granule neurones (CGNs) culture was examined. Treatment for 48 h with METH or MDMA (1-5 mM) induced a higher decrease in viability than 24 h treatment. z.VAD.fmk (100 μM) but not MK-801 nor NBQX recovered control viability values. In both cases, cell death was characterised as apoptotic rather than necrotic by morphology cell observation. Apoptosis measured by flow cytometry indicated an increase in the hypodiploid population after 48 h treatment with METH and MDMA. Apoptosis was reverted by the presence of z.VAD.fmk (100 μM) but not by 10 μM MK-801 or NBQX. Similar results were obtained by analysing nuclear chromatine condensation. These results ruled out excitotoxic participation in amphetamine derivative-induced neurotoxicity in CGNs. Participation of radical oxygen species (ROS) was evaluated using α-tocopherol (1-15 μM) and cytometric studies. The co-treatment with 4 mM METH or MDMA for 48 h partially reverted neurotoxic action and apoptotic features, indicating ROS implication in CGNs death by amphetamine derivatives. Alteration of mitochondrial function induced cytochrome C (Cyt C) release after 48-h treatment with METH and MDMA (4 mM). There was also indication of caspase-3-like activation, measured by immunoanalysis and biochemically. Finally, neurodegenerative action caused by amphetamine derivatives may be prevented by using caspase inhibitors

  7. Khat use and appetite: An overview and comparison of amphetamine, khat and cathinone

    Science.gov (United States)

    Lemieux, Andrine M.; Li, Bingshuo; al’Absi, Mustafa

    2014-01-01

    Ethnopharmacological relevance To understand the role of khat (Catha edulis) use on the aberrations in appetite and weight which are common comorbidities for khat and other amphetamine users. Materials and methods We provide a comprehensive overview and conceptual summary of the historical cultural use of khat as a natural stimulant and describe the similarities and differences between cathinone (the main psychoactive constituent of khat) and amphetamine highlighting the limited literature on the neurophysiology of appetite and subsequent weight effects of khat. Results Animal and some human studies indicate that khat produces appetite suppression, although little is known about mechanisms of this effect. Both direct and indirect effects of khat stem from multiple factors including behavioral, chemical and neurophysiological effects on appetite and metabolism. Classic and newly identified appetite hormones have not been explored sufficiently in the study of appetite and khat use. Unique methodological challenges and opportunities are encountered when examining effects of khat and cathinone including khat-specific medical comorbidities, unique route of administration, differential patterns of behavioral effects relative to amphetamines and the nascent state of our understanding of the neurobiology of this drug. Conclusion A considerable amount of work remains in the study of the appetite effects of khat chewing and outline a program of research that could inform our understanding of this natural amphetamine’s appetite effects and help prepare health care workers for the unique health effects of this drug. PMID:25435289

  8. Increased BOLD activation to predator stressor in subiculum and midbrain of amphetamine-sensitized maternal rats.

    Science.gov (United States)

    Febo, Marcelo; Pira, Ashley S

    2011-03-25

    Amphetamine, which is known to cause sensitization, potentiates the hormonal and neurobiological signatures of stress and may also increase sensitivity to stress-inducing stimuli in limbic areas. Trimethylthiazoline (5μL TMT) is a chemical constituent of fox feces that evokes innate fear and activates the neuronal and hormonal signatures of stress in rats. We used blood oxygen level dependent (BOLD) MRI to test whether amphetamine sensitization (1mg/kg, i.p. ×3days) in female rats has a lasting effect on the neural response to a stress-evoking stimulus, the scent of a predator, during the postpartum period. The subiculum and dopamine-enriched midbrain VTA/SN of amphetamine-sensitized but not control mothers showed a greater BOLD signal response to predator odor than a control putrid scent. The greater responsiveness of these two brain regions following stimulant sensitization might impact neural processing in response to stressors in the maternal brain. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Presentation of regional cerebral blood flow in amphetamine abusers by 99Tcm-HMPAO brain SPECT

    International Nuclear Information System (INIS)

    Kao, C.H.; Wang, S.J.; Yeh, S.H.

    1994-01-01

    The aim of this study was to describe the effectiveness of 99 Tc m -hexamethylpropyleneamine oxime ( 99 Tc m -HMPAO) brain single photon emission computed tomography (SPECT) in the assessment of the regional cerebral blood flow (rCBF) in amphetamine abusers. Twenty-one amphetamine abusers were included and 99 Tc m -HMPAO brain SPECT performed to evaluate rCBF. The drug-using periods ranged from 1 month to several years. The demonstrated neuropsychogenic symptoms and signs of the abusers were from normal presentation to various neurologic complications. The brain SPECT scans were interpreted visually as either normal or abnormal. The degree of abnormality was classified into mild or severe. The results revealed that (a) most SPECT studies in abusers show small defects (95%, 20/21 cases); 71% (15/21) of cases revealed multiple defects over both hemispheres (classified as severe); 24% (5/21) of the cases had focal defects (classified as mild); and only one case (5%, 1/21) demonstrated a normal SPECT finding; (b) the degree of abnormality on SPECT scans was not related to the dose and duration of drug use or the severity of the neuropsychiatric symptoms and signs. In conclusion, 99 Tc m -HMPAO brain SPECT is a sensitive but not specific test for neuropsychogenic abnormalities associated with amphetamine abuse. (Author)

  10. Clinical Characteristics and Outcomes of Patients with Amphetamine-Associated Cardiomyopathy in South Auckland, New Zealand.

    Science.gov (United States)

    Kueh, Shaw-Hua Anthony; Gabriel, Ruvin S; Lund, Mayanna; Sutton, Tim; Bradley, Joshua; Kerr, Andrew J; Looi, Jen-Li

    2016-11-01

    Amphetamine-associated cardiomyopathy (AAC) is becoming an increasingly recognised entity. The characteristics and outcomes of these patients are poorly understood. Thirty patients admitted with heart failure and echocardiographic evidence of cardiomyopathy between 2005 and 2014 and who had a documented history of amphetamine abuse that was considered an important factor in the causation of their cardiomyopathy were retrospectively identified. Mean age at presentation was 40±10 years with a male predominance (n=25, 83%). The majority were of indigenous Maori ethnicity. At presentation, four patients were in cardiogenic shock. Five patients required intensive care unit (ICU) admission for inotropic support and mechanical ventilation. Fifteen had severe left ventricular (LV) dilation (mean LV end-diastolic dimension 6.8±1.0cm) and all patients had severe LV dysfunction (mean LV ejection fraction 22±8%). Despite optimal heart failure therapy, LV size remained significantly dilated with minimal improvement in LV function. During median follow-up of 18 months, five patients died from end-stage heart failure and 17 had at least one readmission with decompensated heart failure. Amphetamine-associated cardiomyopathy was seen predominantly in young indigenous Maori men. They presented with severe cardiomyopathy, often requiring ICU admission. Severe LV dilation and significant LV dysfunction persisted despite treatment and mortality was high. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  11. Different reactivities of amphetamines with N-methyl-bis(trifluoroacetamide) in heated gas chromatographic injectors.

    Science.gov (United States)

    Hidvégi, E; Hideg, Zs; Somogyi, G P

    2008-03-01

    A fast gas chromatographic mass spectrometric method has been developed earlier for the determination of amphetamine derivatives in human serum and urine. For derivatization, N-methyl-bis(trifluoroacetamide) (MBTFA) was used. Derivatization was performed using an on-line mode, since 1 microl of MBTFA and 1 microl sample extract, dissolved in toluene were injected simultaneously. In this study, the reactivity of the several amphetamine type analytes with MBTFA was investigated. MBTFA used for flash derivatization was applied undiluted on the one hand and diluted 4--4096-fold with acetonitrile on the other hand. Studying several amphetamines in the test sample spiked at the same concentrations we found that they could be divided into 3 groups based on relative target ion peak areas as a function of MBTFA dilution. Group 1, containing only primary amines showed an early increase of the relative peak areas if we increased MBTFA concentration, where group 2 (mainly N-methyl secondary amines) showed that relative peak areas started to increase intensively at higher MBTFA concentrations. Finally, MDEA as an N-ethyl secondary amine, representing group 3, showed significant increase if only slightly diluted MBTFA was used as a flash reagent. This phenomenon can be explained mainly with the less and less reactivity of amine groups in the case of groups 2 and 3, compared to group 1. These findings could help to optimise analytical methods involving flash derivatization processes.

  12. Withdrawal from chronic exposure to amphetamine, but not nicotine, leads to an immediate and enduring deficit in motivated behavior without affecting social interaction in rats

    OpenAIRE

    Der-Avakian, Andre; Markou, Athina

    2010-01-01

    Psychostimulant withdrawal leads to depressive symptoms, such as anhedonia and social dysfunction. We determined the effects of withdrawal from chronic exposure to nicotine (9 mg/kg/day salt, 28 days) or amphetamine (10 mg/kg/day salt, 7 days) on the motivated response for a sucrose reward and on social interaction in rats. Both nicotine and amphetamine exposure increased the motivated response for sucrose. However, only spontaneous amphetamine withdrawal led to an immediate and persistent de...

  13. Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist.

    Science.gov (United States)

    Fuller, R W; Hemrick-Luecke, S K; Ornstein, P L

    1992-10-01

    LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.

  14. PKC phosphorylates residues in the N-terminal of the DA transporter to regulate amphetamine-induced DA efflux.

    Science.gov (United States)

    Wang, Qiang; Bubula, Nancy; Brown, Jason; Wang, Yunliang; Kondev, Veronika; Vezina, Paul

    2016-05-27

    The DA transporter (DAT), a phosphoprotein, controls extracellular dopamine (DA) levels in the central nervous system through transport or reverse transport (efflux). Multiple lines of evidence support the claim that PKC significantly contributes to amphetamine-induced DA efflux. Other signaling pathways, involving CaMKII and ERK, have also been shown to regulate DAT mediated efflux. Here we assessed the contribution of putative PKC residues (S4, S7, S13) in the N-terminal of the DAT to amphetamine-induced DA efflux by transfecting DATs containing different serine to alanine (S-A) point mutations into DA pre-loaded HEK-293 cells and incubating these cells in amphetamine (2μM). The effects of a S-A mutation at the non-PKC residue S12 and a threonine to alanine (T-A) mutation at the ERK T53 residue were also assessed for comparison. WT-DATs were used as controls. In an initial experiment, we confirmed that inhibiting PKC with Go6976 (130nM) significantly reduced amphetamine-induced DA efflux. In subsequent experiments, cells transfected with the S4A, S12A, S13A, T53A and S4,7,13A mutants showed a reduction in amphetamine-induced DA efflux similar to that observed with Go6976. Interestingly, cells transfected with the S7A mutant, identified by some as a PKC-PKA residue, showed unperturbed WT-DAT levels of amphetamine-induced DA efflux. These results indicate that phosphorylation by PKC of select residues in the DAT N-terminal can regulate amphetamine-induced efflux. PKC can act either independently or in concert with other kinases such as ERK to produce this effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Evidence for fibroblast growth factor-2 as a mediator of amphetamine-enhanced motor improvement following stroke.

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    William A Wolf

    Full Text Available Previously we have shown that addition of amphetamine to physical therapy results in enhanced motor improvement following stroke in rats, which was associated with the formation of new motor pathways from cortical projection neurons of the contralesional cortex. It is unclear what mechanisms are involved, but amphetamine is known to induce the neuronal release of catecholamines as well as upregulate fibroblast growth factor-2 (FGF-2 expression in the brain. Since FGF-2 has been widely documented to stimulate neurite outgrowth, the present studies were undertaken to provide evidence for FGF-2 as a neurobiological mechanism underlying amphetamine-induced neuroplasticity. In the present study rats that received amphetamine plus physical therapy following permanent middle cerebral artery occlusion exhibited significantly greater motor improvement over animals receiving physical therapy alone. Amphetamine plus physical therapy also significantly increased the number of FGF-2 expressing pyramidal neurons of the contralesional cortex at 2 weeks post-stroke and resulted in significant axonal outgrowth from these neurons at 8 weeks post-stroke. Since amphetamine is a known releaser of norepinephrine, in vitro analyses focused on whether noradrenergic stimulation could lead to neurite outgrowth in a manner requiring FGF-2 activity. Primary cortical neurons did not respond to direct stimulation by norepinephrine or amphetamine with increased neurite outgrowth. However, conditioned media from astrocytes exposed to norepinephrine or isoproterenol (a beta adrenergic agonist significantly increased neurite outgrowth when applied to neuronal cultures. Adrenergic agonists also upregulated FGF-2 expression in astrocytes. Pharmacological analysis indicated that beta receptors and alpha1, but not alpha2, receptors were involved in both effects. Antibody neutralization studies demonstrated that FGF-2 was a critical contributor to neurite outgrowth induced by

  16. Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists

    Directory of Open Access Journals (Sweden)

    Andrew John Dudley Nelson

    2013-05-01

    Full Text Available Repeated exposure to the psychostimulant amphetamine has been shown to disrupt goal-directed instrumental actions and promote the early and abnormal development of goal-insensitive habitual responding (Nelson and Killcross, 2006. To investigate the neuropharmacological specificity of this effect as well as restore goal-directed responding in animals with pre-training amphetamine exposure, animals were treated with the non-selective dopamine antagonist α-flupenthixol, the selective D1 antagonist SCH 23390 or the selective D2 antagonist eticlopride, prior to instrumental training (3 sessions. Subsequently, the reinforcer was paired with LiCL-induced gastric-malaise and animals were given a test of goal-sensitivity both in extinction and reacquisition. The effect of these dopaminergic antagonists on the sensitivity of lever press performance to outcome devaluation was assessed in animals with pre-training exposure to amphetamine (Experiments 1a-1c or in non-sensitized animals (Experiment 2. Both α-flupenthixol and SCH23390 reversed accelerated habit formation following amphetamine sensitization. However, eticlopride appeared to enhance this effect and render instrumental performance compulsive as these animals were unable to inhibit responding both in extinction and reacquisition, even though a consumption test confirmed they had acquired an aversion to the reinforcer. These findings demonstrate that amphetamine induced-disruption of goal-directed behaviour is mediated by activity at distinct dopamine receptor subtypes and may represent a putative model of the neurochemical processes involved in the loss of voluntary control over behaviour.

  17. The amphetamine sensitization model of schizophrenia symptoms and its effect on schedule-induced polydipsia in the rat.

    Science.gov (United States)

    Hawken, Emily R; Beninger, Richard J

    2014-05-01

    Amphetamine enhances dopamine (DA) transmission and induces psychotic states or exacerbates psychosis in at-risk individuals. Amphetamine sensitization of the DA system has been proposed as a rodent model of schizophrenia-like symptoms. In humans, excessive nonphysiologic drinking or primary polydipsia is significantly associated with a diagnosis of schizophrenia. In rodents, nonphysiologic drinking can be induced by intermittent presentation of food in the presence of a drinking spout to a hungry animal; this phenomenon is termed, "schedule-induced polydipsia" (SIP). This study aims to determine the effects of amphetamine sensitization on SIP. We injected rats with amphetamine (1.5 mg/kg) daily for 5 days. Following 4 weeks of withdrawal, animals were food restricted and exposed to the SIP protocol (noncontingent fixed-time 1-min food schedule) for daily 2-h sessions for 24 days. Results showed that previously amphetamine-injected animals drank more in the SIP protocol and drank more than controls when the intermittent food presentation schedule was removed. These findings suggest that hyperdopaminergia associated with schizophrenia may contribute to the development of polydipsia in this population. Whether animals that develop SIP have DA dysfunction or aberrant activity of other circuits that modulate DA activity has yet to be clearly defined.

  18. The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities.

    Science.gov (United States)

    Faraone, Stephen V

    2018-04-01

    Psychostimulants, including amphetamines and methylphenidate, are first-line pharmacotherapies for individuals with attention-deficit/hyperactivity disorder (ADHD). This review aims to educate physicians regarding differences in pharmacology and mechanisms of action between amphetamine and methylphenidate, thus enhancing physician understanding of psychostimulants and their use in managing individuals with ADHD who may have comorbid psychiatric conditions. A systematic literature review of PubMed was conducted in April 2017, focusing on cellular- and brain system-level effects of amphetamine and methylphenidate. The primary pharmacologic effect of both amphetamine and methylphenidate is to increase central dopamine and norepinephrine activity, which impacts executive and attentional function. Amphetamine actions include dopamine and norepinephrine transporter inhibition, vesicular monoamine transporter 2 (VMAT-2) inhibition, and monoamine oxidase activity inhibition. Methylphenidate actions include dopamine and norepinephrine transporter inhibition, agonist activity at the serotonin type 1A receptor, and redistribution of the VMAT-2. There is also evidence for interactions with glutamate and opioid systems. Clinical implications of these actions in individuals with ADHD with comorbid depression, anxiety, substance use disorder, and sleep disturbances are discussed. Copyright © 2018 The Author. Published by Elsevier Ltd.. All rights reserved.

  19. Segmental analysis of amphetamines in hair using a sensitive UHPLC-MS/MS method.

    Science.gov (United States)

    Jakobsson, Gerd; Kronstrand, Robert

    2014-06-01

    A sensitive and robust ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine and 3,4-methylenedioxy methamphetamine in hair samples. Segmented hair (10 mg) was incubated in 2M sodium hydroxide (80°C, 10 min) before liquid-liquid extraction with isooctane followed by centrifugation and evaporation of the organic phase to dryness. The residue was reconstituted in methanol:formate buffer pH 3 (20:80). The total run time was 4 min and after optimization of UHPLC-MS/MS-parameters validation included selectivity, matrix effects, recovery, process efficiency, calibration model and range, lower limit of quantification, precision and bias. The calibration curve ranged from 0.02 to 12.5 ng/mg, and the recovery was between 62 and 83%. During validation the bias was less than ±7% and the imprecision was less than 5% for all analytes. In routine analysis, fortified control samples demonstrated an imprecision <13% and control samples made from authentic hair demonstrated an imprecision <26%. The method was applied to samples from a controlled study of amphetamine intake as well as forensic hair samples previously analyzed with an ultra high performance liquid chromatography time of flight mass spectrometry (UHPLC-TOF-MS) screening method. The proposed method was suitable for quantification of these drugs in forensic cases including violent crimes, autopsy cases, drug testing and re-granting of driving licences. This study also demonstrated that if hair samples are divided into several short segments, the time point for intake of a small dose of amphetamine can be estimated, which might be useful when drug facilitated crimes are investigated. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Use of amphetamine by recreational users of ecstasy (MDMA) is associated with reduced striatal dopamine transporter densities: a [123I]beta-CIT SPECT study--preliminary report

    NARCIS (Netherlands)

    Reneman, Liesbeth; Booij, Jan; Lavalaye, Jules; de Bruin, Kora; Reitsma, Johannes B.; Gunning, BoudewijnW; den Heeten, Gerard J.; van den Brink, Wim

    2002-01-01

    RATIONALE: Tablets sold as ecstasy often contain not only 3,4-methylenedioxymethamphetamine (MDMA) but other compounds well known to cause dopaminergic neurotoxicity, such as (meth)amphetamine. Furthermore, the use of ecstasy in the Netherlands is often combined with the use of amphetamine. However,

  1. Novel Selectivity-Based Forensic Toxicological Validation of a Paper Spray Mass Spectrometry Method for the Quantitative Determination of Eight Amphetamines in Whole Blood

    NARCIS (Netherlands)

    Teunissen, Sebastiaan F.; Fedick, Patrick W.; Berendsen, Bjorn J.A.; Nielen, Michel W.F.; Eberlin, Marcos N.; Graham Cooks, R.; Asten, van Arian C.

    2017-01-01

    Paper spray tandem mass spectrometry is used to identify and quantify eight individual amphetamines in whole blood in 1.3 min. The method has been optimized and fully validated according to forensic toxicology guidelines, for the quantification of amphetamine, methamphetamine,

  2. Amphetamines and cannabinoids testing in hair: Evaluation of results from a two-year period.

    Science.gov (United States)

    Burgueño, María José; Alonso, Amaya; Sánchez, Sergio

    2016-08-01

    This paper presents an overview of a set of amphetamines and cannabinoids tests performed on head hair samples from the Medico-Legal sector at the Madrid Department of the Spanish National Institute of Toxicology and Forensic Sciences during the years 2013 and 2014. The hair samples were tested for five stimulant phenylalkylamine derivatives -amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy-amphetamine (MDA), and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)- and/or two cannabinoids-Δ(9)-tetrahydrocannabinol (THC) and cannabinol (CBN)- by gas chromatography equipped with mass spectrometry detection in selected-ion monitoring mode, applying a method accredited to ISO/IEC 17025 standards. The test results were interpreted according to the confirmation cut-offs proposed by the Society of Hair Testing (SoHT) to identify chronic drug use. The ratios of positive results were studied in relation to gender, age, hair colour, dyeing and length of the tested samples to assess the independence from these variables or the association with them. Low, medium and high ranges of concentration were also estimated for each drug. 21.94% of the 2954 hair samples tested for phenylalkylamine derivatives were positive for one or more substances. 16.38% of the samples were positive for AP, 12.09% for MDMA and only 0.44% for MA. 6.60% of the tested samples were positive for AP/MDMA combination. A total of 3178 samples were tested for cannabinoids, resulting in 53.40% positive for THC and CBN. Simultaneous tests for phenylalkylamine derivatives and cannabinoids were performed in 2931 of the samples; 14.94% of them were positive for THC, CBN, and one or more amphetamines. According to the results from the statistical analysis, the use of THC and MDMA vary with age and gender among the Medico-Legal sector in an extended area of Spain, while the use of AP appears to be independent of these variables. On the other hand, the results of THC in

  3. A rapid novel derivatization of amphetamine and methamphetamine using 2,2,2-trichloroethyl chloroformate for gas chromatography electron ionization and chemical ionization mass spectrometric analysis.

    Science.gov (United States)

    Dasgupta, A; Spies, J

    1998-05-01

    Amphetamine and methamphetamine are commonly abused central nervous system stimulants. We describe a rapid new derivatization of amphetamine and methamphetamine using 2,2,2-trichloroethyl chloroformate for gas chromatography-mass spectrometric analysis. Amphetamine and methamphetamine, along with N-propyl amphetamine (internal standard), were extracted from urine using 1-chlorobutane. The derivatization with 2,2,2-trichloroethyl chloroformate can be achieved at room temperature in 10 minutes. The electron ionization mass spectrum of amphetamine 2,2,2-trichloroethyl carbamate showed two weak molecular ions at m/z 309 and 311, but showed diagnostic strong peaks at m/z 218, 220, and 222. In contrast, chemical ionization of the mass spectrum of amphetamine 2,2,2-trichloroethyl carbamate showed strong (M + 1) ions at m/z 310 and 312 and other strong diagnostic peaks at m/z 274 and 276. The major advantages of this derivative are the presence of a diagnostic cluster of peaks due to the isotopic effect of three chlorine atoms (isotopes 35 and 37) in the derivatized molecule and the relative ease of its preparation. We also observed strong molecular ions for derivatized methamphetamine in the chemical ionization mass spectrum, but the molecular ions were very weak in the electron ionization mass spectrum. We used the scan mode of mass spectrometry in all analyses. When using a urine standard containing 1,000 ng/mL of amphetamine (a 7.4-micromol/L concentration) and methamphetamine (a 6.7-micromol/L concentration), the within-run precisions were 4.8% for amphetamine and 3.6% for methamphetamine. The corresponding between-run precisions were 5.3% for amphetamine and 6.7% for methamphetamine. The assay was linear for amphetamine and methamphetamine concentrations of 250 to 5,000 ng/mL (amphetamine, 1.9-37.0 micromol/L; methamphetamine, 1.7-33.6 micromol/L). The detection limit was 100 ng/mL (amphetamine, 0.74 micromol/L; methamphetamine, 0.67 micromol/L) using the scan mode

  4. Amphetamine concentrations in human urine following single-dose administration of the calcium antagonist prenylamine-studies using fluorescence polarization immunoassay (FPIA) and GC-MS.

    Science.gov (United States)

    Kraemer, Thomas; Roditis, Susanne K; Peters, Frank T; Maurer, Hans H

    2003-03-01

    Prenylamine (R,S-N-(3,3-diphenylpropyl-methyl-2-phenethylamine), a World Health Organization class V calcium antagonist, is known to be metabolized to amphetamine. In this study, amphetamine concentrations after a single-dose administration of prenylamine were determined to check if they reached values that could be of analytical and/or pharmacological importance in clinical and forensic toxicology. Enantiomeric composition of amphetamine was also studied. Five volunteers received a single 120-mg oral dose of prenylamine. Urine samples were analyzed using the Abbott TDx immunoassay Amphetamine/Methamphetamine II and using our routine systematic toxicological analysis (STA) gas chromatography-mass spectrometry (GC-MS) procedure. For quantitation purposes, GC-MS was used in the selected-ion monitoring (SIM) mode (ions m/z 118, 122, 240, 244) after solid-phase extraction (Isolute Confirm HCX) and derivatization (heptafluorobutyric anhydride). Amphetamine-d5 was used as internal standard (IS). Chiral separation of the heptafluorobutyrated amphetamine enantiomers was achieved using an Astec Chiraldex G-PN column. The TDx results showed a great variability for the different volunteers. A urine sample of one volunteer showed results as high as 3200 ng/mL, whereas the urine samples of another volunteer never gave results greater than the TDx detection limit (100 ng/mL). Using the STA procedure, the presence of amphetamine could be confirmed in all urine samples with TDx results greater than the cutoff value (300 ng/mL). Using the GC-MS SIM method, amphetamine concentrations up to 1280 ng/mL were determined. Chiral analysis revealed that both enantiomers of amphetamine were present in the samples with a surplus of the S(+)-enantiomer in the early phase of excretion. Forensic implications are discussed.

  5. Responding for sucrose and wheel-running reinforcement: effect of D-amphetamine.

    Science.gov (United States)

    Belke, T W; Oldford, A C; Forgie, M Y; Beye, J A

    2005-07-01

    The present study assessed the effect of D-amphetamine on responding maintained by wheel-running and sucrose reinforcement. Six male albino Wistar rats were placed in running wheels and exposed to a fixed-interval 30-s schedule that produced either a drop of 5% sucrose solution or the opportunity to run for 15 s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. Doses of 0.25, 0.5, 1.0, 1.5, and 3.0 mg/kg D-amphetamine were administered by i.p. injection 20 min prior to a session. As the dose increased, index of curvature values decreased toward zero and rate-dependency plots revealed increases in lower rates early in the interval and decreases in higher rates toward the end of the interval. Effects were similar in the presence of both stimuli. However, an analysis of post-reinforcement pauses and local response rates broken down by transitions revealed a differential effect. As the dose increased, local response rates following a wheel-running reinforcer were affected more than those following a sucrose reinforcer.

  6. Cocaine versus food choice procedure in rats: environmental manipulations and effects of amphetamine.

    Science.gov (United States)

    Thomsen, Morgane; Barrett, Andrew C; Negus, S Stevens; Caine, S Barak

    2013-03-01

    We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine-choice dose-effect curves (0-1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine-reinforced lever was not affected significantly by removal of cocaine-associated visual or auditory cues, but it was decreased after removal of response-contingent or response-independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d-amphetamine treatment on cocaine choice. Acute and chronic d-amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys. © Society for the Experimental Analysis of Behavior.

  7. Effects of methylphenidate during emotional processing in amphetamine users: preliminary findings.

    Science.gov (United States)

    Bottelier, M A; Schouw, M L J; de Ruiter, M B; Ruhe, H G; Lindauer, R J L; Reneman, L

    2015-12-01

    D-amphetamine (dAMPH) and methylphenidate (MPH) are stimulants used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Preclinical studies have shown that in healthy animals, dAMPH induces dopamine (DA) dysfunction, as evidenced for instance by loss of DA levels and its transporters. It has also been suggested that DA plays an important role in emotional processing, and that altered DA-ergic intervention may modulate amygdala function. To explore the role of the DA system in emotional processing we examined emotional processing using functional magnetic resonance imaging (fMRI) in eight male recreational users of dAMPH and eight male healthy controls. We compared brain activation between both groups during an emotional face-processing task with and without an oral MPH challenge. All subjects were abstinent for at least 2 weeks during the baseline scan. The second scan was performed on the same day 1½ hours after receiving an oral dose of 35 mg MPH. A significant Valence*Group interaction (p = .037) indicated amygdala hyperreactivity to fearful facial expressions in dAMPH users that was robust against adjustment for age (p = .015). Furthermore, duration of amphetamine use in years was positively correlated with amygdala reactivity in dAMPH users (r = .76; p = .029). These exploratory findings are in line with previous findings suggesting that DA plays a role in emotional processing.

  8. Antipsychotic activity of aqueous ethanolic extract of Tinospora Cordifolia in amphetamine challenged mice model

    Directory of Open Access Journals (Sweden)

    Bindu nee Giri Jain

    2010-01-01

    Full Text Available Tinospora cordifolia is reported to have CNS active principle and is used for the treatment of various neurological disorders. Hence, the effect of aqueous ethanolic extract of Tinospora cordifolia was investigated for its putative antipsychotic activity using amphetamine challenged mice model. Haloperidol (1 mg/kg i.p. was administered acutely to mice as standard drug. Control animals received vehicle (10% DMSO. The in vivo receptor binding studies were carried out to correlate the antipsychotic activity of the extract with its capacity to bind to the DAD2 receptor. The results in SLA showed that the hydro alcoholic extract of the stems of Tinospora cordifolia at a dose level of 250 mg/kg and 500 mg/kg showed no significant antipsychotic activity in amphetamine induced hyperactivity in mice when compared to standard. Extract alone treated group at a dos level of 250 mg/kg and 500 mg/kg showed a decreased in locomotor activity when compared to the control. The plant extract increased the DAD2 receptor binding in a dose dependent manner in treated mice compared to the control group.

  9. History of childhood adversity is positively associated with ventral striatal dopamine responses to amphetamine.

    Science.gov (United States)

    Oswald, Lynn M; Wand, Gary S; Kuwabara, Hiroto; Wong, Dean F; Zhu, Shijun; Brasic, James R

    2014-06-01

    Childhood exposure to severe or chronic trauma is an important risk factor for the later development of adult mental health problems, such as substance abuse. Even in nonclinical samples of healthy adults, persons with a history of significant childhood adversity seem to experience greater psychological distress than those without this history. Evidence from rodent studies suggests that early life stress may impair dopamine function in ways that increase risks for drug abuse. However, the degree to which these findings translate to other species remains unclear. This study was conducted to examine associations between childhood adversity and dopamine and subjective responses to amphetamine in humans. Following intake assessment, 28 healthy male and female adults, aged 18-29 years, underwent two consecutive 90-min positron emission tomography studies with high specific activity [(11)C]raclopride. The first scan was preceded by intravenous saline; the second by amphetamine (AMPH 0.3 mg/kg). Consistent with prior literature, findings showed positive associations between childhood trauma and current levels of perceived stress. Moreover, greater number of traumatic events and higher levels of perceived stress were each associated with higher ventral striatal dopamine responses to AMPH. Findings of mediation analyses further showed that a portion of the relationship between childhood trauma and dopamine release may be mediated by perceived stress. Overall, results are consistent with preclinical findings suggesting that early trauma may lead to enhanced sensitivity to psychostimulants and that this mechanism may underlie increased vulnerability for drug abuse.

  10. The role of the GABA system in amphetamine-type stimulant use disorders

    Directory of Open Access Journals (Sweden)

    Dongliang eJiao

    2015-05-01

    Full Text Available Abuse of amphetamine-type stimulants (ATS has become a global public health problem. ATS causes severe neurotoxicity, which could lead to addiction and could induce psychotic disorders or cognitive dysfunctions. However, until now, there has been a lack of effective medicines for treating ATS-related problems. Findings from recent studies indicate that in addition to the traditional dopamine-ergic system, the GABA (gamma-aminobutyric acid-ergic system plays an important role in ATS abuse. However the exact mechanisms of the GABA-ergic system in amphetamine-type stimulant use disorders are not fully understood. This review discusses the role of the GABA-ergic system in ATS use disorders, including ATS induced psychotic disorders and cognitive dysfunctions. We conclude that the GABA-ergic system are importantly involved in the development of ATS use disorders through multiple pathways, and that therapies or medicines that target specific members of the GABA-ergic system may be novel effective interventions for the treatment of ATS use disorders.

  11. Which amphetamine-type stimulants can be detected by oral fluid immunoassays?

    Science.gov (United States)

    Souza, Daniele Z; Boehl, Paula O; Comiran, Eloisa; Prusch, Débora S; Zancanaro, Ivomar; Fuentefria, Alexandre M; Pechansky, Flavio; Duarte, Paulina C A V; De Boni, Raquel B; Fröehlich, Pedro E; Limberger, Renata P

    2012-02-01

    The use of oral fluid for monitoring drug consumption on roads has many advantages over conventional biological fluids; therefore, several immunoassays have been developed for this purpose. In this work, the ability of 3 commercial immunoassays to detect amphetamine-type stimulants (ATSs) in oral fluid was assessed. In addition, it was reviewed the main controlled ATSs available worldwide, as well as the oral fluid immunological screening tests that have been used for identifying ATSs in drivers. The analytical specificity of amphetamine direct enzyme-linked immunosorbent assay (ELISA), methamphetamine direct ELISA (Immunalysis Corporation), and Oral-View saliva multidrug of abuse test (Alfa Scientific Designs) was evaluated using ATS-spiked oral fluid. Legislation and published articles that report the use of immunological screening tests to detect ATS consumption in conductors were reviewed, including the kit's technical information, project reports, police and drug databases. Even at high concentrations, the tested assays were not able to detect methylphenidate, fenproporex, or diethylpropion, controlled ATSs legally marketed in many countries. This evidences the need to develop new kits that enable one to control the misuse of prescription ATSs on roads through oral fluid immunoassays.

  12. Amphetamine in rat brain after intraperitoneal injection of N-alkylated analogues.

    Science.gov (United States)

    Nazarali, A J; Baker, G B; Coutts, R T; Pasutto, F M

    1983-01-01

    Three N-alkylated analogues of amphetamine were administered intraperitoneally to male Sprague-Dawley rats and whole brain levels of amphetamine (AM) and the N-alkyl analogue were determined one hour after injection of the N-alkylated compounds. The drugs administered were the N-2-cyanoethyl-(I) (fenproporex), the N-3-chloropropyl-(II) (mefenorex) and the N-n-propyl-(III) derivatives of AM: the first two of these are used clinically as anorexiants, and the latter has been used extensively to study aspects of metabolism of AM-like compounds. Analysis of AM, I, II and III was performed using electron-capture gas chromatography with a capillary column after reaction of compounds with pentafluorobenzoyl chloride under aqueous conditions. In a second comparative study, equimolar doses (0.05 mMole/kg) of I or AM were administered intraperitoneally to the rats and brain levels determined after one hour. Results indicate extensive N-dealkylation occurs for compounds I, II and III in the rat.

  13. Cocaine Versus Food Choice Procedure in Rats: Environmental Manipulations and Effects of Amphetamine

    Science.gov (United States)

    Thomsen, Morgane; Barrett, Andrew C.; Negus, S. Stevens; Caine, S. Barak

    2014-01-01

    We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine-choice dose-effect curves (0–1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine-reinforced lever was not affected significantly by removal of cocaine-associated visual or auditory cues, but it was decreased after removal of response-contingent or response-independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d-amphetamine treatment on cocaine choice. Acute and chronic d-amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys. PMID:23319458

  14. Association of Cocaine- and Amphetamine-Regulated Transcript (CART) Messenger RNA Level, Food Intake, and Growth in Channel Catfish

    Science.gov (United States)

    Cocaine-and Amphetamine-Regulated Transcript (CART) is a potent hypothalamic anorectic peptide in mammals and fish. We hypothesized that increased food intake is associated with changes in expression of CART mRNA within the brain of channel catfish. Objectives were to clone the CART gene, examine ...

  15. Adolescent THC exposure does not sensitize conditioned place preferences to subthreshold d-amphetamine in male and female rats.

    Science.gov (United States)

    Keeley, Robin J; Bye, Cameron; Trow, Jan; McDonald, Robert J

    2018-01-01

    The acute effects of marijuana consumption on brain physiology and behaviour are well documented, but the long-term effects of its chronic use are less well known. Chronic marijuana use during adolescence is of increased interest, given that the majority of individuals first use marijuana during this developmental stage , and  adolescent marijuana use is thought to increase the susceptibility to abusing other drugs when exposed later in life. It is possible that marijuana use during critical periods in adolescence could lead to increased sensitivity to other drugs of abuse later on. To test this, we chronically administered ∆ 9 -tetrahydrocannabinol (THC) to male and female Long-Evans (LER) and Wistar (WR) rats directly after puberty onset. Rats matured to postnatal day 90 before being exposed to a conditioned place preference task (CPP). A subthreshold dose of d-amphetamine, found not to induce place preference in drug naïve rats, was used as the unconditioned stimulus. The effect of d-amphetamine on neural activity was inferred by quantifying cfos expression in the nucleus accumbens and dorsal hippocampus following CPP training. Chronic exposure to THC post-puberty had no potentiating effect on a subthreshold dose of d-amphetamine to induce CPP. No differences in cfos expression were observed. These results show that chronic exposure to THC during puberty did not increase sensitivity to d-amphetamine in adult LER and WR rats. This supports the concept that THC may not sensitize the response to all drugs of abuse.

  16. Adulterants and diluents in heroin, amphetamine, and cocaine found on the illicit drug market in Aarhus, Denmark

    DEFF Research Database (Denmark)

    Andreasen, Mette Findal; Lindholst, Christian; Kaa, Elisabet

    2009-01-01

    of adulterants and diluents present in the drugs. Results are compared with a similar study conducted ten years earlier. The concentrations of the active substances in illicit heroin, amphetamine, and cocaine samples have decreased significantly over a 10-year period. This finding shows that the "cutting...

  17. Calmodulin kinase II interacts with the dopamine transporter C terminus to regulate amphetamine-induced reverse transport

    DEFF Research Database (Denmark)

    Fog, Jacob U; Khoshbouei, Habibeh; Holy, Marion

    2006-01-01

    Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the d...

  18. Effectiveness and safety of amphetamine for ADHD in population between 6 and 19 years: a systematic review

    Directory of Open Access Journals (Sweden)

    José Calleja

    2012-09-01

    Full Text Available Introduction: Attention deficit hyperactivity disorder (ADHD drug treatment is based on psychostimulants, and methylphenidate is still the most widely used one. Other psychostimulants used include amphetamines, hence the importance of knowing both its effectiveness and safety. Purpose: To identify, synthesize and evaluate the best available evidence on the effectiveness and safety of amphetamine in ADHD in the 6-19 year-old population. Methods: A systematic review of studies that evaluated the effectiveness of interventions comparing amphetamine to methylphenidate was conducted. The outcomes measured were educational performance, psychosocial functioning, quality of life and adverse effects. The following databases were searched up to February 2012 in English and Spanish: PubMed/MEDLINE, LILACS, Cochrane, DARE and National Guideline Clearinghouse. The articles that met inclusion criteria were assessed by two researchers independently. Results: Of the 114 studies found initially, four were included, among which a systematic review, a primary article and two clinical guidelines. Conclusions: The evidence on amphetamine for ADHD treatment recommends its use as an alternative to MPH. Further good-quality studies are needed.

  19. Glycogen synthase kinase-3β inhibition in the medial prefrontal cortex mediates paradoxical amphetamine action in a mouse model of ADHD

    Directory of Open Access Journals (Sweden)

    Yi-Chun eYen

    2015-03-01

    Full Text Available Psychostimulants show therapeutic efficacy in the treatment of attention-deficit hyperactivity disorder (ADHD. It is generally assumed that they ameliorate ADHD symptoms via interfering with monoaminergic signaling. We combined behavioral pharmacology, neurochemistry and molecular analyses to identify mechanisms underlying the paradoxical calming effect of amphetamine in low trait anxiety behavior (LAB mice, a novel multigenetic animal model of ADHD. Amphetamine (1 mg/kg and methylphenidate (10 mg/kg elicited similar dopamine and norepinephrine release in the medial prefrontal cortex (mPFC and in the striatum of LAB mice. In contrast, amphetamine decreased, while methylphenidate increased locomotor activity. This argues against changes in dopamine and/or norepinephrine release as mediators of amphetamine paradoxical effects. Instead, the calming activity of amphetamine corresponded to the inhibition of glycogen synthase kinase3β (GSK3β activity, specifically in the mPFC. Accordingly, not only systemic administration of the GSK3β inhibitor TDZD-8 (20 mg/kg, but also local microinjections of TDZD-8 and amphetamine into the mPFC, but not into the striatum, decreased locomotor activity in LAB mice. Amphetamine effects seem to depend on NMDA receptor signaling, since pre- or co-treatment with MK-801 (0.3 mg/kg abolished the effects of amphetamine (1 mg/kg on the locomotion and on the phosphorylation of GSK3β at the level of the mPFC. Taken together, the paradoxical calming effect of amphetamine in hyperactive LAB mice concurs with a decreased GSK3β activity in the mPFC. This effect appears to be independent of dopamine or norepinephrine release, but contingent on NMDA receptor signaling.

  20. CRISIS UNDER THE RADAR: ILLICIT AMPHETAMINE USE IS REACHING EPIDEMIC PROPORTIONS AND CONTRIBUTING TO RESOURCE OVER-UTILIZATION AT A LEVEL 1 TRAUMA CENTER.

    Science.gov (United States)

    Gemma, Vincent A; Chapple, Kristina A; Goslar, Pamela W; Israr, Sharjeel; Petersen, Scott R; Weinberg, Jordan A

    2018-05-21

    Trauma centers reported illicit amphetamine use in approximately 10% of trauma admissions in the previous decade. From experience at a trauma center located in a southwestern metropolis, our perception is that illicit amphetamine use is on the rise, and that these patients utilize in-hospital resources beyond what would be expected for their injuries. The purpose of this study was to document the incidence of illicit amphetamine use among our trauma patients and to evaluate its impact on resource utilization. We conducted a retrospective cohort study using 7 consecutive years of data (starting July 2010) from our institution's trauma registry. Toxicology screenings were used to categorize patients into one of three groups: illicit amphetamine, other drugs, or drug free. Adjusted linear and logistic regression models were used to predict hospital cost, length of stay, ICU admission and ventilation between drug groups. Models were conducted with combined injury severity (ISS) and then repeated for ISS <9, ISS 9-15 and ISS 16 and above. 8,589 patients were categorized into the following three toxicology groups: 1255 (14.6%) illicit amphetamine, 2214 (25.8%) other drugs, and 5120 (59.6%) drug free. Illicit amphetamine use increased threefold over the course of the study (from 7.85% to 25.0% of annual trauma admissions). Adjusted linear models demonstrated that illicit amphetamine among patients with ISS<9 was associated with 4.6% increase in hospital cost (P=.019) and 7.4% increase in LOS (P=.043). Logistic models revealed significantly increased odds of ventilation across all ISS groups and increased odds of ICU admission when all ISS groups were combined (P=.001) and within the ISS<9 group (P=.002). Hospital resource utilization of amphetamine patients with minor injuries is significant. Trauma centers with similar epidemic growth in proportion of amphetamine patients face a potentially significant resource strain relative to other centers. Prognostic and

  1. Effect of D-amphetamine on emotion-potentiated startle in healthy humans: implications for psychopathy and antisocial behaviour.

    Science.gov (United States)

    Corr, Philip J; Kumari, Veena

    2013-01-01

    An emerging literature associates increased dopaminergic neurotransmission with altered brain response to aversive stimuli in humans. The direction of the effect of dopamine on aversive motivation, however, remains unclear, with some studies reporting increased and others decreased amygdala activation to aversive stimuli following the administration of dopamine agonists. Potentiation of the startle response by aversive foreground stimuli provides an objective and directional measure of emotional reactivity and is considered useful as an index of the emotional effects of different drugs. We investigated the effects of two doses of D-amphetamine (5 and 10 mg), compared to placebo, for the first time to our knowledge, using the affect-startle paradigm. The study employed a between-subjects, double-blind design, with three conditions: 0 mg (placebo), and 5 and 10 mg D-amphetamine (initially n = 20/group; final sample: n = 18, placebo; n = 18, 5 mg; n = 16, 10 mg). After drug/placebo administration, startle responses (eyeblinks) to intermittent noise probes were measured during viewing of pleasant, neutral and unpleasant images. Participants' general and specific impulsivity and fear-related personality traits were also assessed. The three groups were comparable on personality traits. Only the placebo group showed significant startle potentiation by unpleasant, relative to neutral, images; this effect was absent in both 5- and 10-mg D-amphetamine groups (i.e. the same effect of D-amphetamine observed at different doses in different people). Our findings demonstrate a reduced aversive emotional response under D-amphetamine and may help to account for the known link between the use of psychostimulant drugs and antisocial behaviour.

  2. REM sleep deprivation produces a motivational deficit for food reward that is reversed by intra-accumbens amphetamine in rats.

    Science.gov (United States)

    Hanlon, Erin C; Benca, Ruth M; Baldo, Brian A; Kelley, Ann E

    2010-10-30

    Prolonged sleep deprivation in rats produces a characteristic syndrome of increase in food intake accompanied by, paradoxically, decrease in weight, suggesting a potential alteration in motivation for food reward. Using the multiple platform method to produce REM sleep deprivation (REMSD), we investigated the effect of REMSD on motivation for food reinforcement with a progressive ratio operant task, which yields a measure of the motor effort that a hungry animal is willing to expend to obtain food (the point at which the animal quits responding is termed the "break-point"). We found that REMSD rats decreased the break point for sucrose pellet reinforcement in comparison to controls, as revealed by a within-session decline in responding. This behavioral deficit is similar to that observed in rats with diminished dopamine transmission within the nucleus accumbens (Acb), and, considering that stimulants are frequently used in the clinical setting to reverse the effects of sleepiness, we examined the effect of systemic or intra-Acb amphetamine on break point in REMSD rats. Animals were given either systemic or intra-Acb amphetamine injections on days 3 and 5 of REMSD. Systemic amphetamine (0.1, 0.5, or 2.5mg/kg) did not increase break point in REMSD rats. In contrast, intra-Acb infusions of amphetamine (1, 10, or 30μg/0.5μl bilaterally) reversed the REMSD-induced suppression of progressive ratio responding. Specifically, the two higher doses of intra-Acb amphetamine were able to prolong responding within the session (resulting in an increased break point) on day 3 of REMSD while only the highest dose was sufficient following 5 days of REMSD. These data suggest that decreased motivation for food reward caused by REMSD may result from a suppression of dopamine function in the Acb. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Changes of cytosolic calcium and contractility of young rat vas deferens by acute treatment with amphetamine, fluoxetine or sibutramine.

    Science.gov (United States)

    Jurkiewicz, Neide Hyppolito; da Silva Júnior, Edilson Dantas; de Souza, Bruno Palmieri; Ferreira Verde, Luciana; Drawanz Pereira, Janaina; Mendes Sobrinho, Cairo; Soubhi Smaili, Soraya; Caricati-Neto, Afonso; Miranda-Ferreira, Regiane; Jurkiewicz, Aron

    2012-09-15

    Previous studies conducted in our laboratory indicated that administration of amphetamine, fluoxetine or sibutramine affects the sympathetic nervous system of the rat vas deferens. Therefore, our goal was to verify the role of calcium in vasa deferentia from young rats pretreated with a single dose of these drugs. Young 40-day-old male Wistar rats were pretreated with amphetamine 3 mg/kg, fluoxetine 10 mg/kg or sibutramine 6 mg/kg for 4 h before the experiments. CaCl(2) (10 mM) was used to induce contraction through time-effect curves in calcium-free solution to measure phasic and tonic components. We also evaluated the calcium-induced fluorescence of vas deferens cut into thin slices. In rats pretreated with amphetamine, we found an increase of the tonic contraction component which was reduced by verapamil. The phasic and tonic responses were increased in the group treated with fluoxetine, but only the tonic response was more sensitive to the antagonism by verapamil. The group treated with sibutramine showed an increase of phasic response whereas the tonic component was decreased. In this group an increase of the affinity for verapamil antagonism was found. In the calcium fluorescence study it was observed that the group treated with amphetamine, fluoxetine or sibutramine showed higher basal Ca(2+) fluorescence after stimulus with KCl (70 mM), noradrenaline (10(-4)M) or acetylcholine (10(-4)M). In all pretreated groups the calcium fluorescence was diminished by nifedipine 10(-7)M. Therefore, the pretreatment with amphetamine, fluoxetine or sibutramine seems to affect the calcium contractility and homeostasis in young rat vas deferens. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Headspace liquid-phase microextraction of methamphetamine and amphetamine in urine by an aqueous drop

    International Nuclear Information System (INIS)

    He Yi; Vargas, Angelica; Kang, Youn-Jung

    2007-01-01

    This study developed a headspace liquid-phase microextraction (LPME) method by using a single aqueous drop in combination with high performance liquid chromatography (HPLC)-UV detection for the determination of methamphetamine (MAP) and amphetamine (AP) in urine samples. The analytes, volatile and basic, were released from sample matrix into the headspace first, and then protonated and dissolved in an aqueous H 3 PO 4 drop hanging in the headspace by a HPLC syringe. After extraction, this drop was directly injected into HPLC. Parameters affecting extraction efficiency were investigated and optimized. This method showed good linearity in the investigated concentration range of 1.0-1500 μg L -1 , repeatability of the extraction (R.S.D. -1 for both analytes). Enrichment factors of about 400-fold and 220-fold were achieved for MAP and AP, respectively, at optimum conditions. The feasibility of the method was demonstrated by analyzing human urine samples

  5. Evidence that alpha-methyl-p-tyramine is implicated in behavioural augmentation to amphetamine.

    Science.gov (United States)

    Dougan, D F; Labrie, S L; Paull, P D; Duffield, P H; Wade, D N

    1986-01-01

    Behavioural studies showed that administration of alpha-methyl-p-tyramine (AMT; 10 mg/kg i.p.) to rats 24 hr before treatment with d-amphetamine (AMPHET; 4 mg/kg i.p.) resulted in augmentation of AMPHET-induced stereotype activity. Parallel experiments involving electro-chemical estimation of dopamine metabolites in the striatum showed that the decrease in the concentration of homovanillic acid (HVA) produced by AMPHET (4 mg/kg) was enhanced in AMT (10 mg/kg) pretreated animals. These findings suggest that AMT derived from previous doses of AMPHET may play a role in the phenomena of behavioural augmentation observed after chronic administration of AMPHET.

  6. Contribution of the dorsal noradrenergic bundle to the effect of amphetamine on acetylcholine turnover

    International Nuclear Information System (INIS)

    Robinson, S.E.

    1986-01-01

    In order to determine the contribution of the noradrenergic projections of the locus coeruleus to the action of amphetamine on cholinergic neurons in several areas of the brain, the dorsal noradrenergic bundle was selectively lesioned by injection of the neurotoxin 6-hydroxydopamine. The bundles of Equithesin-anesthetized male rats were lesioned bilaterally by stereotaxically-placed injections of 6-OHDA. The animals were killed in the microwave and constant rate infusion with phosphoryl ( 2 H 9 )-choline was begun. Levels of ACh and choline and TR /SUB ACh/ were determined by a mass fragmentographic technique. Rats not exhibiting the proper decrease in NE were excluded from all data calculations. It is shown that noradrenergic neurons travelling in the dorsal noradrenergic bundle do not exert a tonic action on cholinergic neurons in the cortex, hippocampus or hypothalamus

  7. Cardiovascular manifestations of substance abuse: part 2: alcohol, amphetamines, heroin, cannabis, and caffeine.

    Science.gov (United States)

    Frishman, William H; Del Vecchio, Alexander; Sanal, Shirin; Ismail, Anjum

    2003-01-01

    The abuse of alcohol is associated with chronic cardiomyopathy, hypertension, and arrhythmia. Abstinence or using alcohol in moderation can reverse these cardiovascular problems. Alcohol is also distinguished among the substances of abuse by having possible protective effects against coronary artery disease and stroke when used in moderate amounts. Amphetamines (eg, speed, ice, ecstasy) have many of the cardiovascular toxicities seen with cocaine, including acute and chronic cardiovascular diseases. Heroin and other opiates can cause arrhythmias and noncardiac pulmonary edema, and may reduce cardiac output. Cardiovascular problems are less common with cannabis (marijuana) than with opiates, but major cognitive disorders may be seen with its chronic use. It is still controversial whether caffeine can cause hypertension and coronary artery disease, and questions have been raised about its safety in patients with heart failure and arrhythmia.

  8. Predicting hydration free energies of amphetamine-type stimulants with a customized molecular model

    International Nuclear Information System (INIS)

    Li, Jipeng; Lu, Diannan; Fu, Jia; Wu, Jianzhong; Huang, Xing

    2016-01-01

    Amphetamine-type stimulants (ATS) are a group of incitation and psychedelic drugs affecting the central nervous system. Physicochemical data for these compounds are essential for understanding the stimulating mechanism, for assessing their environmental impacts, and for developing new drug detection methods. However, experimental data are scarce due to tight regulation of such illicit drugs, yet conventional methods to estimate their properties are often unreliable. Here we introduce a tailor-made multiscale procedure for predicting the hydration free energies and the solvation structures of ATS molecules by a combination of first principles calculations and the classical density functional theory. We demonstrate that the multiscale procedure performs well for a training set with similar molecular characteristics and yields good agreement with a testing set not used in the training. The theoretical predictions serve as a benchmark for the missing experimental data and, importantly, provide microscopic insights into manipulating the hydrophobicity of ATS compounds by chemical modifications. (paper)

  9. Comparison of radioimmunoassay and gas chromatographic mass spectrometric assay for d-amphetamine

    International Nuclear Information System (INIS)

    Powers, K.H.; Ebert, M.H.

    1979-01-01

    Quantification of low levels of psychotropic drugs (10 -7 to 10 -9 g ml -1 ) in small volumes of plasma requires sensitive and accurate methods. Validation of these methods is best achieved by comparing results obtained using several techniques. In this study, amphetamine levels in plasma were measured using gas chromatography mass spectrometry and radioimmunoassay. Correlation of the results obtained by the two methods was found to be positive and high (R = 0.9822). The average coefficient of variation between assays for gas chromatography mass spectrometry was 5.8% and for radioimmunoassay was 12.3%, while the average coefficient of variation within assays for gas chromatography mass spectrometry was 4.9% and for radioimmunoassay 6.9%. Although gas chromatography mass spectrometry was 1.9 times more sensitive than radioimmunoassay, for most purposes, the convenience of the radioimmunoassay method outweighs the technical superiority of gas chromatography mass spectrometry. (author)

  10. Single-photon emission tomography (SPECT) with 123I-amphetamine in cerebral ischemia

    International Nuclear Information System (INIS)

    Koenig, B.; Donis, J.; Mostbeck, A.; Koehn, H.

    1987-01-01

    The uptake of 123 I-amphetamine (IMP) in brain mainly corresponds to regional perfusion. Distribution of IMP can be visualized in tomographic slices by single-photon emission computed tomography (SPECT). For better evaluation and comparison in follow-up studies, right/left ratios were computed and an asymmetry index calculated. The most sensitive asymmetry index was achieved by 120 average circumferential profiles. In 52 patients with stroke and 16 controls the respective sensitivities of IMP-SPECT, computed tomography (CT), static and dynamic brain scanning and angiography were evaluated. In patients with TIA and PRIND the IMP-SPECT had the highest sensitivity of all non-invasive methods. In patients with completed stroke, the sensitivity of IMP-SPECT was comparable with that of CT (90 vs. 93%). There was a significant correlation between the IMP asymmetry index and the clinical and social score (p [de

  11. Differentiation of ring-substituted regioisomers of amphetamine and methamphetamine by supercritical fluid chromatography.

    Science.gov (United States)

    Segawa, Hiroki; T Iwata, Yuko; Yamamuro, Tadashi; Kuwayama, Kenji; Tsujikawa, Kenji; Kanamori, Tatsuyuki; Inoue, Hiroyuki

    2017-03-01

    Chromatographic differentiation of the ring-substituted regioisomers of amphetamine (AMP) and methamphetamine (MA) was performed by supercritical fluid chromatography (SFC). The behaviour of the retention against the changes of column temperature and co-solvent proportion was studied. The obtained information facilitated the optimization of the each regioisomer. As a result, 2-, 3-, and 4-ring-substituted analogues of AMP and MA with methyl, methoxy, fluoro, chloro, and bromo groups were separated, generally within 6 min. In addition, we found that the separation pattern of the examined regioisomers was classified into two, which depended on the electron donating/withdrawing effect of the substituent. Our results indicate that SFC could be used in forensic drug analysis for fast, reliable identification of structurally similar drugs of abuse. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. The influence of social structure on social isolation in amphetamine-treated Java monkeys (Macaca fascicularis).

    Science.gov (United States)

    Knobbout, D.A.; Ellenbroek, B.A.; Cools, A.R.

    1996-10-01

    Amphetamine-induced social isolation in monkeys has often been considered a valid animal model for certain negative symptoms of schizophrenia. However, there appear to be many ambiguities in relation to the exact nature of the isolation. Therefore, the effect of orally administered amphetamine (AMP) on the occurrence of social isolation in Java monkeys was studied. In part I the rank dependency of the effects of AMP (0.5mg/kg) was investigated in four alpha-males and three beta-males. AMP increased 'proximity' and 'passive groom', and decreased 'active allogroom' in alpha-males. In contrast, AMP decreased all three behavioural elements to a certain extent in beta-males. It is concluded that AMP induces social isolation in beta-males, but not in alpha-males. In part II of this study the AMP-induced behaviour of the treated monkey and the simultaneously occurring changes in the non-treated monkeys were investigated in a detailed study of a single social group. AMP significantly reduced the frequency of 'exploration', 'locomotion', 'self-groom', 'swing', 'active groom', 'inspect', 'approach' and originally-present stereotypies. Thus AMP apparently reduces the ability to initiate behaviour which is characteristic for the adult animal. AMP did not affect the frequency of 'present' and 'play' and enhanced that of 'aggression' and 'fear' in the beta-male; it also elicited various juvenile-like behaviours in both alpha- and beta-males, suggesting that AMP induces a behavioural regression. Furthermore, the behaviour of the non-treated monkeys of the group was decisive for the occurrence of social isolation of the treated monkey. Thus, the effects of AMP on the social behaviour of Java monkeys depend on the individual sensitivity, the social position which the subject occupies in its group, and the behaviour of the partners of the treated subject.

  13. Bioanalysis for cocaine, opiates, methadone, and amphetamines exposure detection during pregnancy.

    Science.gov (United States)

    Concheiro, Marta; Lendoiro, Elena; de Castro, Ana; Gónzalez-Colmenero, Eva; Concheiro-Guisan, Ana; Peñas-Silva, Patricia; Macias-Cortiña, Manuel; Cruz-Landeira, Angelines; López-Rivadulla, Manuel

    2017-06-01

    Drug exposure during pregnancy constitutes a major legal issue and a public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta, and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography-tandem mass spectrometry for the determination of cocaine, opioids, methadone, and amphetamines, and compared the analytical results from the four different matrices. The cases were divided in non-exposure, low, and frequent exposure, based on maternal hair concentrations and segmental analysis by trimesters. For cocaine, 62 cases tested positive in hair, 9 in meconium, 6 in placenta and 7 in umbilical cord. In the case of opioids, 14 maternal hair cases were positive, 11 meconium and umbilical cord and 9 placenta samples. For methadone, 11 cases were positive in hair, 9 in meconium and 6 in placenta and umbilical cord. For amphetamines, 18 cases were positive according to maternal hair, but all meconium, placenta, and umbilical cord tested negative. Maternal hair was the most sensitive specimen to detect drug exposure during pregnancy. Meconium, placenta, and umbilical cord tested positive if hair concentrations showed frequent drug use during the whole pregnancy, especially during the third trimester. Meconium, placenta, and umbilical cord also tested positive for morphine and metabolites, if this drug was administered during labour and delivery. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Differential effects of psychomotor stimulants on attentional performance in rats: nicotine, amphetamine, caffeine and methylphenidate.

    Science.gov (United States)

    Bizarro, L; Patel, S; Murtagh, C; Stolerman, I P

    2004-05-01

    Nicotine can improve attentional performance in the rat as assessed by a modified five-choice serial reaction time task (5-CSRTT), but it is not known if the effect is shared with other psychomotor stimulants. This study compared the effects of nicotine, amphetamine, caffeine and methylphenidate on performance in the 5-CSRTT and determined whether presenting stimuli at unpredictable times by using variable inter-trial intervals (ITI) influenced the sensitivity of the task to the drugs. One group of male hooded rats was trained to obtain food reinforcers by nose-poking in response to 1 s light stimuli presented randomly in one of five apertures, with fixed ITI; for a second group of rats, ITI varied randomly (n=12 per group). As observed previously, nicotine (tested in doses of 0.05-0.2 mg/kg) produced dose-related improvements in accuracy, reduced omission errors and response latencies, but increased anticipatory responding. Amphetamine (0.1-0.8 mg/kg) and methylphenidate (2.5-10 mg/kg) increased accuracy and reduced response latency, and decreased anticipatory responding. Caffeine (2.5-20 mg/kg) did not improve performance except at a small dose that decreased omission errors only. Training at different levels of stimulus predictability influenced performance in the undrugged state but had little impact on profiles of responses to the drugs. The findings with methylphenidate support the potential value of the 5-CSRTT for testing drugs that may be useful in the treatment of attention deficit hyperactivity disorder.

  15. New chlorinated amphetamine-type-stimulants disinfection-by-products formed during drinking water treatment.

    Science.gov (United States)

    Huerta-Fontela, Maria; Pineda, Oriol; Ventura, Francesc; Galceran, Maria Teresa

    2012-06-15

    Previous studies have demonstrated high removal rates of amphetamine-type-stimulants (ATSs) through conventional drinking water treatments; however the behaviour of these compounds through disinfection steps and their transformation into disinfection-by-products (DBPs) is still unknown. In this work, for the first time, the reactivity of some ATSs such as amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA) with chlorine has been investigated under simulated and real drinking water treatment conditions in order to evaluate their ability to give rise to transformation products. Two new DBPs from these illicit drugs have been found. A common chlorinated-by-product (3-chlorobenzo)-1,3-dioxole, was identified for both MDA and MDEA while for MDMA, 3-chlorocatechol was found. The presence of these DBPs in water samples collected through drinking water treatment was studied in order to evaluate their formation under real conditions. Both compounds were generated through treatment from raw river water samples containing ATSs at concentration levels ranging from 1 to 15 ng/L for MDA and from 2.3 to 78 ng/L for MDMA. One of them, (3-chlorobenzo)-1,3-dioxole, found after the first chlorination step, was eliminated after ozone and GAC treatment while the MDMA DBP mainly generated after the postchlorination step, showed to be recalcitrant and it was found in final treated waters at concentrations ranging from 0.5 to 5.8 ng/L. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine.

    Science.gov (United States)

    Ahn, Kyung-Heup; Sewell, Andrew; Elander, Jacqueline; Pittman, Brian; Ranganathan, Mohini; Gunduz-Bruce, Handan; Krystal, John; D'Souza, Deepak Cyril

    2015-11-01

    Some schizophrenia patients are more sensitive to amphetamine (AMPH)-induced exacerbations in psychosis-an effect that correlates with higher striatal dopamine release. This enhanced vulnerability may be related to gamma-aminobutyric acid (GABA) deficits observed in schizophrenia. We hypothesized that a pharmacologically induced GABA deficit would create vulnerability to the psychotomimetic effects to the 'subthreshold' dose of AMPH in healthy subjects, which by itself would not induce clinically significant increase in positive symptoms. To test this hypothesis, a GABA deficit was induced by intravenous infusion of iomazenil (IOM; 3.7 μg/kg), an antagonist and partial inverse agonist of benzodiazepine receptor. A subthreshold dose of AMPH (0.1 mg/kg) was administered by intravenous infusion. Healthy subjects received placebo IOM followed by placebo AMPH, active IOM followed by placebo AMPH, placebo IOM followed by active AMPH, and active IOM followed by active AMPH in a randomized, double-blind crossover design over 4 test days. Twelve healthy subjects who had a subclinical response to active AMPH alone were included in the analysis. Psychotomimetic effects (Positive and Negative Syndrome Scale (PANSS)), perceptual alterations (Clinician Administered Dissociative Symptoms Scale (CADSS)), and subjective effects (visual analog scale) were captured before and after the administration of drugs. IOM significantly augmented AMPH-induced peak changes in PANSS positive symptom subscale and both subjective and objective CADSS scores. There were no pharmacokinetic interactions. In conclusion, GABA deficits increased vulnerability to amphetamine-induced psychosis-relevant effects in healthy subjects, suggesting that pre-existing GABA deficits may explain why a subgroup of schizophrenia patients are vulnerable to AMPH.

  17. Withdrawal from chronic exposure to amphetamine, but not nicotine, leads to an immediate and enduring deficit in motivated behavior without affecting social interaction in rats.

    Science.gov (United States)

    Der-Avakian, Andre; Markou, Athina

    2010-07-01

    Psychostimulant withdrawal leads to depressive symptoms, such as anhedonia and social dysfunction. We determined the effects of withdrawal from chronic exposure to nicotine (9 mg/kg/day salt, 28 days) or amphetamine (10 mg/kg/day salt, 7 days) on the motivated response for a sucrose reward and on social interaction in rats. Both nicotine and amphetamine exposure increased the motivated response for sucrose. However, only spontaneous amphetamine withdrawal led to an immediate and persistent decrease in motivated behavior, which was not correlated with body weight loss. Social interaction was not affected during withdrawal from either drug. These results indicate that withdrawal from chronic amphetamine exposure leads to an immediate and enduring anhedonic state.

  18. Amphetamine self-administration and dopamine function: assessment of gene × environment interactions in Lewis and Fischer 344 rats.

    Science.gov (United States)

    Meyer, Andrew C; Bardo, Michael T

    2015-07-01

    Previous research suggests both genetic and environmental influences on substance abuse vulnerability. The current work sought to investigate the interaction of genes and environment on the acquisition of amphetamine self-administration as well as amphetamine-stimulated dopamine (DA) release in nucleus accumbens shell using in vivo microdialysis. Inbred Lewis (LEW) and Fischer (F344) rat strains were raised in either an enriched condition (EC), social condition (SC), or isolated condition (IC). Acquisition of amphetamine self-administration (0.1 mg/kg/infusion) was determined across an incrementing daily fixed ratio (FR) schedule. In a separate cohort of rats, extracellular DA and the metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in the nucleus accumbens shell following an acute amphetamine injection (1 mg/kg). "Addiction-prone" LEW rats had greater acquisition of amphetamine self-administration on a FR1 schedule compared to "addiction-resistant" F344 rats when raised in the SC environment. These genetic differences were negated in both the EC and IC environments, with enrichment buffering against self-administration and isolation enhancing self-administration in both strains. On a FR5 schedule, the isolation-induced increase in amphetamine self-administration was greater in F344 than LEW rats. While no group differences were obtained in extracellular DA, gene × environment differences were obtained in extracellular levels of the metabolite DOPAC. In IC rats only, LEW rats showed attenuation in the amphetamine-induced decrease in DOPAC compared to F344 rats. IC LEW rats also had an attenuated DOPAC response to amphetamine compared to EC LEW rats. The current results demonstrate gene × environment interactions in amphetamine self-administration and amphetamine-induced changes in extracellular DOPAC in nucleus accumbens (NAc) shell. However, the behavioral and neurochemical differences were not related directly, indicating that

  19. Novelty response and 50 kHz ultrasonic vocalizations: Differential prediction of locomotor and affective response to amphetamine in Sprague-Dawley rats.

    Science.gov (United States)

    Garcia, Erik J; Cain, Mary E

    2016-02-01

    Novelty and sensation seeking (NSS) predisposes humans and rats to experiment with psychostimulants. In animal models, different tests of NSS predict different phases of drug dependence. Ultrasonic vocalizations (USVs) are evoked by psychomotor stimulants and measure the affective/motivation response to stimuli, yet the role NSS has on USVs in response to amphetamine is not determined. The aim of the present study was to determine if individual differences in NSS and USVs can predict locomotor and USV response to amphetamine (0.0, 0.3, and 1.0 mg/kg) after acute and chronic exposure. Thirty male rats were tested for their response to novelty (IEN), choice to engage in novelty (NPP), and heterospecific play (H-USV). Rats were administered non-contingent amphetamine or saline for seven exposures, and USVs and locomotor activity were measured. After a 14-day rest, rats were administered a challenge dose of amphetamine. Regression analyses indicated that amphetamine dose-dependently increased locomotor activity and the NPP test negatively predicted treatment-induced locomotor activity. The H-USV test predicted treatment-induced frequency-modulated (FM) USVs, but the strength of prediction depended on IEN response. Results provide evidence that locomotor activity and FM USVs induced by amphetamine represent different behavioral responses. The prediction of amphetamine-induced FM USVs by the H-USV screen was changed by the novelty response, indicating that the affective value of amphetamine-measured by FM USVs-depends on novelty response. This provides evidence that higher novelty responders may develop a tolerance faster and may escalate intake faster.

  20. Fenproporex N-dealkylation to amphetamine--enantioselective in vitro studies in human liver microsomes as well as enantioselective in vivo studies in Wistar and Dark Agouti rats.

    Science.gov (United States)

    Kraemer, Thomas; Pflugmann, Thomas; Bossmann, Michael; Kneller, Nicole M; Peters, Frank T; Paul, Liane D; Springer, Dietmar; Staack, Roland F; Maurer, Hans H

    2004-09-01

    Fenproporex (FP) is known to be N-dealkylated to R(-)-amphetamine (AM) and S(+)-amphetamine. Involvement of the polymorphic cytochrome P450 (CYP) isoform CYP2D6 in metabolism of such amphetamine precursors is discussed controversially in literature. In this study, the human hepatic CYPs involved in FP dealkylation were identified using recombinant CYPs and human liver microsomes (HLM). These studies revealed that not only CYP2D6 but also CYP1A2, CYP2B6 and CYP3A4 catalyzed this metabolic reaction for both enantiomers with slight preference for the S(+)-enantiomer. Formation of amphetamine was not significantly changed by quinidine and was not different in poor metabolizer HLM compared to pooled HLM. As in vivo experiments, blood levels of R(-)-amphetamine and S(+)-amphetamine formed after administration of FP were determined in female Dark Agouti rats (fDA), a model of the human CYP2D6 poor metabolizer phenotype (PM), male Dark Agouti rats (mDA), an intermediate model, and in male Wistar rats (WI), a model of the human CYP2D6 extensive metabolizer phenotype. Analysis of the plasma samples showed that fDA exhibited significantly higher plasma levels of both amphetamine enantiomers compared to those of WI. Corresponding plasma levels in mDA were between those in fDA and WI. Furthermore, pretreatment of WI with the CYP2D inhibitor quinine resulted in significantly higher amphetamine plasma levels, which did not significantly differ from those in fDA. The in vivo studies suggested that CYP2D6 is not crucial to the N-dealkylation but to another metabolic step, most probably to the ring hydroxylation. Further studies are necessary for elucidating the role of CYP2D6 in FP hydroxylation.

  1. Effect of (+)-amphetamine on the retention of 3H-catecholamines in slices of normal and reserpinized rat brain and heart

    International Nuclear Information System (INIS)

    Ross, S.B.; Renyi, A.L.

    1978-01-01

    The effect of reserpine on the inhibition by (+)-amphetamine and cocaine of the accumulation of 3 H-dopamine (DA) in striatal slices and 3 H-noradrenaline (NA) in slices of cerebral occipital cortex and heart atrium of rats and the release of the 3 H-amines from these tissues were examined. Reserpine (5 mg/kg intraperitoneally) was injected 18 hours before the experiments. It was found that reserpine markedly enhanced the in vitro potency of amphetamine in the striatum and heart but only slightly in the cortex. After administration in vivo (+)-amphetamine was about 10 times more potent in reducing the amine accumulation in the cortex as in the striatum. Reserpine enhanced the effect in both regions. The inhibitory potency of cocaine in vitro was unchanged by reserpine in the striatum but was reduced in the cortex and heart. Reserpine did not change the inhibitory potency of desipramine in the cortex and heart. The release of the 3 H-amines by (+)-amphetamine was enhanced by reserpine in the striatum and heart but the small release produced in the cortex was not increased. The release produced by cocaine was similarly enhanced by reserpine but cocaine was much less active than (+)-amphetamine. The results indicate that (+)-amphetamine and cocaine inhibit the amine accumulation by different mechanisms. (author)

  2. [Effect of chlorpromazine and amphetamine on incidental memory and its relation to the introvert-extravert structure of personality].

    Science.gov (United States)

    Zaimov, K; Kokoshkarova, A

    1978-10-01

    A total of fifty-four test subjects divided into one control group and two experimental groups were used to study the effects of chlorpromazine and amphetamine upon the incidental memory, its accuracy, and possible dependence on the introversive or extroversive personality structure, respectively. It has been found that chlorpromazine tends to lessen the incidental memory in extent and increase the number of allomnesias or instances of inaccurate remembrance, whereas amphetamine has the effects of increasing the extent of the incidental memory and reducing the number of allomnesias. A comparison of the extent of the incidental memory with the structure of personality in respect of introversion or extroversion in the control group also showed significant differences, the incidental memory being of smaller extent in the case of introversion and greater extent in the case of extroversion.

  3. Effects of an acute therapeutic or rewarding dose of amphetamine on acquisition of Pavlovian autoshaping and ventral striatal dopamine signaling.

    Science.gov (United States)

    Schuweiler, D R; Athens, J M; Thompson, J M; Vazhayil, S T; Garris, P A

    2018-01-15

    Rewarding doses of amphetamine increase the amplitude, duration, and frequency of dopamine transients in the ventral striatum. Debate continues at the behavioral level about which component of reward, learning or incentive salience, is signaled by these dopamine transients and thus altered in addiction. The learning hypothesis proposes that rewarding drugs result in pathological overlearning of drug-predictive cues, while the incentive sensitization hypothesis suggests that rewarding drugs result in sensitized attribution of incentive salience to drug-predictive cues. Therapeutic doses of amphetamine, such as those used to treat attention-deficit hyperactivity disorder, are hypothesized to enhance the ventral striatal dopamine transients that are critical for reward-related learning and to enhance Pavlovian learning. However, the effects of therapeutic doses of amphetamine on Pavlovian learning are poorly understood, and the effects on dopamine transients are completely unknown. We determined the effects of an acute pre-training therapeutic or rewarding amphetamine injection on the acquisition of Pavlovian autoshaping in the intact rat. We also determined the effects of these doses on electrically evoked transient-like dopamine signals using fast-scan cyclic voltammetry in the anesthetized rat. The rewarding dose enhanced the amplitude and duration of DA signals, caused acute task disengagement, impaired learning for several days, and triggered incentive sensitization. The therapeutic dose produced smaller enhancements in DA signals but did not have similar behavioral effects. These results underscore the necessity of more studies using therapeutic doses, and suggest a hybrid learning/incentive sensitization model may be required to explain the development of addiction. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Application of gas chromatography-tandem mass spectrometry for the determination of amphetamine-type stimulants in blood and urine.

    Science.gov (United States)

    Woźniak, Mateusz Kacper; Wiergowski, Marek; Aszyk, Justyna; Kubica, Paweł; Namieśnik, Jacek; Biziuk, Marek

    2018-01-30

    Amphetamine, methamphetamine, phentermine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxy-N-ethylamphetamine (MDEA) are the most popular amphetamine-type stimulants. The use of these substances is a serious societal problem worldwide. In this study, a method based on gas chromatography-tandem mass spectrometry (GC-MS/MS) with simple and rapid liquid-liquid extraction (LLE) and derivatization was developed and validated for the simultaneous determination of the six aforementioned amphetamine derivatives in blood and urine. The detection of all compounds was based on multiple reaction monitoring (MRM) transitions. The most important advantage of the method is the minimal sample volume (as low as 200μL) required for the extraction procedure. The validation parameters, i.e., the recovery (90.5-104%), inter-day accuracy (94.2-109.1%) and precision (0.5-5.8%), showed the repeatability and sensitivity of the method for both matrices and indicated that the proposed procedure fulfils internationally established acceptance criteria for bioanalytical methods The procedure was successfully applied to the analysis of real blood and urine samples examined in 22 forensic toxicological cases. To the best of our knowledge, this is the first work presenting the use of GC-MS/MS for the determination of amphetamine-type stimulants in blood and urine. In view of the low limits of detection (0.09-0.81ng/mL), limits of quantification (0.26-2.4ng/mL), and high selectivity, the procedure can be applied for drug monitoring in both fatal and non-fatal intoxication cases in routine toxicology analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Amphetamine Action at the Cocaine- and Antidepressant-Sensitive Serotonin Transporter Is Modulated by αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Montgomery, Therese R; Hofmaier, Tina

    2015-01-01

    Serotonergic neurotransmission is terminated by reuptake of extracellular serotonin (5-HT) by the high-affinity serotonin transporter (SERT). Selective 5-HT reuptake inhibitors (SSRIs) such as fluoxetine or escitalopram inhibit SERT and are currently the principal treatment for depression and anx...... and efflux at monoamine transporters are asymmetric processes that can be targeted separately. Ultimately, this may provide a molecular mechanism for putative drug developments to treat amphetamine addiction....

  6. Some effects of prenatal exposure to d-amphetamine sulfate and phenobarbital on developmental neurochemistry and on behavior.

    Science.gov (United States)

    Zemp, J W; Middaugh, L D

    1975-01-01

    Amphetamine. Prenatal intraperitoneal injection of d-amphetamine sulfate (5 mg/kg) produces decreases in the levels of catecholamines in the brain the day of birth and increases on day 30. Open-field activity from days 12 to 31 was higher for the group of animals injected with amphetamine or saline if scores were totaled across all test days. At day 75 the offspring of amphetamine-injected mothers exhibited altered open-field behavior. The effects were not observed with subcutaneous injection regardless of the dose used (2.5, 5.0, and 10.0 mg/kg). The lowest subcutaneous dose decreases neonatal viability. Phenobarbital. Prenatal intraperitoneal injection of phenobarbital (80 mg/kg) resulted in decreased litter size, increases mortality, and decreased amounts of nucleic acid and protein in the brains of surviving offspring. Behavioral deficits associated with response perseveration could be demonstrated at 60 days in the mice prenatally exposed to this dosage. Subcutaneous injections of phenobarbital to pregnant mice at 80 and 40 mg/kg, but not 20 mg/kg, doses increased neonatal mortality. Mature animals prenatally exposed to 40 mg/kg phenobarbital have altered open-field behavior and differ from control animals on a passive avoidance task. Mature offspring prenatally exposed to the 20 or 40 mg/kg dose also responded less than controls on an operant task requiring an increasing number of responses per reinforcement. These studies suggest that prenatal exposure to phenobarbital has in some way altered the animals' reactivity to stimualtion.

  7. The Role of Hypothalamic Insulin and Dopamine in the Anorectic Effect of Cocaine and d-amphetamine

    Science.gov (United States)

    1992-08-21

    smoking free-base cocaine, or smoking crack, and (5) smoking coca-paste (cocaine-sulfate, usually smoked with tobacco or cannabis ). Cocaine is a...Exposure to cocaine involves a wide variety of physiological, neurochemical, behavioral, and psychological consequences. The pharmacology and toxicology ...agonists. Neuropharmacology, 21, 885-890. Asghar, K., & De Souza, E. (1989). Pharmacology and toxicology of amphetamine and related designer drugs. NIDA

  8. Stimulus properties of nicotine, amphetamine, and chlordiazepoxide as positive features in a pavlovian appetitive discrimination task in rats.

    Science.gov (United States)

    Palmatier, Matthew I; Wilkinson, Jamie L; Metschke, Dawn M; Bevins, Rick A

    2005-04-01

    Recent experiments from our laboratory have demonstrated that drug states can signal when environmental cues will be followed by rewarding outcomes (ie Pavlovian conditioning). However, little is known about the generality of this approach and whether it can be used for studying the pharmacological properties of drug states. Accordingly, the present experiments tested the pharmacological specificity of nicotine (0.4 mg/kg), amphetamine (1 mg/kg), and chlordiazepoxide (CDP, 5 mg/kg) in this Pavlovian drug discrimination procedure. Following drug administration, presentation of a conditional stimulus (CS) was followed by brief access to sucrose. When saline was administered, the same CS was presented but sucrose was withheld. In substitution tests, rats in each condition received varying doses of all training drugs and caffeine. Anticipatory food seeking developed during the CS on drug sessions but not on saline sessions for all drug features (ie drug state-specific conditional response (CR)). In generalization tests, this CR decreased as a function of decreases in the training dose. Median effective doses (ED50s) were calculated for nicotine (0.054 mg/kg), amphetamine (0.26 mg/kg), and CDP (2.48 mg/kg). No compound tested substituted for the CDP training drug. Partial substitution was evident between nicotine and amphetamine; CDP did not substitute for either of these drug features. Caffeine fully substituted for nicotine (ED50 = 15.45 mg/kg) and amphetamine (ED50 = 3.70 mg/kg), but not for CDP. These results are consistent with the hypothesis that drug states can occasion appetitive Pavlovian CRs in a pharmacologically specific manner.

  9. Differential effects of acute amphetamine and phencyclidine treatment and withdrawal from repeated amphetamine or phencyclidine treatment on social interaction and social memory in rats.

    Science.gov (United States)

    Li, Ming; He, Wei; Munro, Rebecca

    2012-06-01

    Although animal models based on amphetamine (AMPH) or phencyclidine (PCP) treatment have been used extensively to study the neurobiological and behavioral characteristics of schizophrenia, there are conflicting reports regarding their validity in modeling the negative symptoms and cognitive deficits of schizophrenia. The present study examined how acute AMPH or PCP treatment (Experiment 1) and withdrawal from repeated AMPH treatment (Experiment 2) or PCP treatment (Experiment 3) affects social behavior and social recognition memory in male Sprague-Dawley rats. Each subject was tested on two consecutive days. On the first day, the rats were tested four times (5 min/each) at 10-min intervals with the same partner rat (termed "AAAA" day). One day later, the rats were tested with the previous partner in the first three sessions and with a new partner rat in the final session (termed "AAAB" day). The results show that acute AMPH treatment (1.5 mg/kg, sc) significantly reduced the time spent on social interaction, but did not affect social recognition on the first day. Acute AMPH only disrupted social recognition on the second day of drug testing. In contrast, acute PCP treatment (2.0 mg/kg, sc) had no effect on time spent on social interaction, but did significantly disrupt social recognition on both days. Withdrawal from repeated AMPH (3.0 mg/kg/day for 7 days, ip) or PCP (5.0 mg/kg/twice daily for 7 days, ip) treatment did not affect social interaction or social recognition, indicating a lack of long-term detrimental effect of repeated AMPH or PCP treatment. These results suggest that acute AMPH treatment at a low dose (1.5 mg/kg) may be useful in modeling social withdrawal symptoms of schizophrenia, whereas acute PCP treatment at a similar dose range (2.0 mg/kg) may be useful in modeling the social cognitive deficit of schizophrenia. © 2012 The Institute of Psychology, Chinese Academy of Sciences and Blackwell Publishing Asia Pty Ltd.

  10. Correlation of individual differences in schizotypal personality traits with amphetamine-induced dopamine release in striatal and extrastriatal brain regions.

    Science.gov (United States)

    Woodward, Neil D; Cowan, Ronald L; Park, Sohee; Ansari, M Sib; Baldwin, Ronald M; Li, Rui; Doop, Mikisha; Kessler, Robert M; Zald, David H

    2011-04-01

    Schizotypal personality traits are associated with schizophrenia spectrum disorders, and individuals with schizophrenia spectrum disorders demonstrate increased dopamine transmission in the striatum. The authors sought to determine whether individual differences in normal variation in schizotypal traits are correlated with dopamine transmission in the striatum and in extrastriatal brain regions. Sixty-three healthy volunteers with no history of psychiatric illness completed the Schizotypal Personality Questionnaire and underwent positron emission tomography imaging with [(18)F]fallypride at baseline and after administration of oral d-amphetamine (0.43 mg/kg). Dopamine release, quantified by subtracting each participant's d-amphetamine scan from his or her baseline scan, was correlated with Schizotypal Personality Questionnaire total and factor scores using region-of-interest and voxel-wise analyses. Dopamine release in the striatum was positively correlated with overall schizotypal traits. The association was especially robust in the associative subdivision of the striatum. Voxel-wise analyses identified additional correlations between dopamine release and schizotypal traits in the left middle frontal gyrus and left supramarginal gyrus. Exploratory analyses of Schizotypal Personality Questionnaire factor scores revealed correlations between dopamine release and disorganized schizotypal traits in the striatum, thalamus, medial prefrontal cortex, temporal lobe, insula, and inferior frontal cortex. The association between dopamine signaling and psychosis phenotypes extends to individual differences in normal variation in schizotypal traits and involves dopamine transmission in both striatal and extrastriatal brain regions. Amphetamine-induced dopamine release may be a useful endophenotype for investigating the genetic basis of schizophrenia spectrum disorders.

  11. Amphetamine-metabolites of deprenyl involved in protection against neurotoxicity induced by MPTP and 2'-methyl-MPTP.

    Science.gov (United States)

    Sziráki, I; Kardos, V; Patthy, M; Pátfalusi, M; Gaál, J; Solti, M; Kollár, E; Singer, J

    1994-01-01

    The ability of 1-deprenyl to protect against the parkinsonian effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been attributed to the inhibition of conversion of MPTP to MPP+ (1-methyl-4-phenylpyridinium) catalyzed by MAO-B. We report here that deprenyl-treatment in mice has an additional neuroprotective element associated with the rapid metabolization of 1-deprenyl to 1-methamphetamine and 1-amphetamine. 1-Methamphetamine and 1-amphetamine inhibit MPP(+)-uptake into striatal synaptosomes prepared from rats. Post-treatment by 1-deprenyl, 1-methamphetamine, 1-amphetamine (at times when MPTP is no longer present in the striatum of mice) protects against neurotoxicity in C57BL mice by blocking the uptake of MPP+ into dopaminergic neurons, and even against the neurotoxicity induced by 2'CH3-MPTP, which is partly bioactivated by MAO-A. These findings may have clinical implications since deprenyl has recently been found to delay the progression of Parkinson's disease.

  12. Amphetamine-enhanced accumulation of [3H]-spiperone in mouse corpus striatum in vivo: Modification by other drugs

    International Nuclear Information System (INIS)

    Dorris, R.L.

    1989-01-01

    Other investigators have reported that amphetamine administered to rodents results in an increase in the in vivo accumulation of either the tritiated dopamine receptor ligand, spiperone or pimozide in the dopaminergic corpus striatum, (specific binding) while not altering that in the sparsely dopaminergically innervated cerebellum (non-specific binding). Experiments were undertaken to determine if the results could be replicated and if some other drugs would modify the effect. Male mice were injected with [ 3 H]-spiperone (20 μCi/Kg, 0.0003 mg/kg) s.c. and killed 2 hrs later for determination of radioactivity in corpus striatum and cerebellum. Amphetamine (20 mg/kg, i.p.) given 15 min before [ 3 H]-spiperone, increased accumulation in striatum but not cerebellum. The increase was inhibited by α - methyltyrosine (α-MT), haloperidol, reserpine or amantadine. It is suggested that the amphetamine-induced increase in accumulation of [ 3 H]-spiperone in corpus striatum (specific binding) depends on release of large amounts of dopamine, which then must be able to interact with the dopamine receptor. The antagonism of the effect by α-MT or reserpine can be explained by dopamine depletion, that of haloperidol by antagonism for binding at the receptor site. It is suggested that amantadine acts by a dual mechanism: (1) as a low efficacy agonist, it competes for binding to the receptor and (2) it has some ability to block dopamine release

  13. Prepulse inhibition of the acoustic startle reflex in pigs and its disruption by D-amphetamine

    DEFF Research Database (Denmark)

    Lind, N. M.; Arnfred, S. M.; Hemmingsen, R. P.

    2004-01-01

    Prepulse inhibition (PPI) of the startle reflex is an operational measure of sensorimotor gating. The dopamine receptor agonist-mediated disruption of PPI in rats is widely used as a model of the sensorimotor gating deficiencies demonstrated in schizophrenia patients. As a possible tool for valid......Prepulse inhibition (PPI) of the startle reflex is an operational measure of sensorimotor gating. The dopamine receptor agonist-mediated disruption of PPI in rats is widely used as a model of the sensorimotor gating deficiencies demonstrated in schizophrenia patients. As a possible tool....../kg with a paradigm including two levels of prepulses (82 and 88dB) and a prepulse (PP) interval of 60 and 120ms. We found an average PPI of the startle reflex of 25.6% and both of the investigated PP intensities and PP intervals were equally effective in this PP-inhibitive paradigm. AMPH significantly disrupted PPI...... and, in spite of only the 0.5mg/kg dose proved statistically significant, the results indicate this to be dose-related. We have demonstrated the phenomenon of PPI of the startle reflex in landrace pigs and its disruption by d-amphetamine. Studies of sensorimotor gating defects could be a valuable...

  14. Simultaneous quantification of cocaine, amphetamines, opiates and cannabinoids in vitreous humor.

    Science.gov (United States)

    Peres, Mariana Dadalto; Pelição, Fabrício Souza; Caleffi, Bruno; De Martinis, Bruno Spinosa

    2014-01-01

    A GC-MS method for simultaneous analysis of cocaine (COC), amphetamines (AMPs), opiates, cannabinoids and their metabolites in vitreous humor (VH) was developed and fully validated. VH samples were extracted using solid phase extraction and injected into the GC-MS, using a selected ion monitoring mode. Linearity ranged from 10 to 1000 ng/mL; the exception was anhydroecgonine methyl ester (AEME), for which linearity ranged from 10 to 750 ng/mL. Inter-assay imprecision lay from 1.2 to 10.0%, intra-assay imprecision was samples taken from individuals whose blood had screened positive for drugs of abuse. All the individuals screened positive for COC in the blood (seven samples) also had positive results in VH; COC concentration ranged from 30.81 to 283.97 ng/mL (mean 186.98 ng/mL) and benzoylecgonine concentration ranged from 11.47 to 460.98 ng/mL (mean 133.91 ng/mL). It was also noticed that, in five cases, cocaethylene was detected. AEME was also quantified in one case. The use of AMP detected by blood analysis was confirmed in the VH of one individual (24.31 ng/mL). However, samples taken from three individuals whose blood tested positive for carboxy-tetrahydrocannabinol presented negative results. The results demonstrated that VH is a suitable alternative biological sample to determine COC, AMPs, opiates and their metabolites.

  15. Neuronal Nicotinic Receptors as New Targets for Amphetamine-Induced Oxidative Damage and Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Elena Escubedo

    2011-06-01

    Full Text Available Amphetamine derivatives such as methamphetamine (METH and 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy” are widely abused drugs in a recreational context. This has led to concern because of the evidence that they are neurotoxic in animal models and cognitive impairments have been described in heavy abusers. The main targets of these drugs are plasmalemmal and vesicular monoamine transporters, leading to reverse transport and increased monoamine efflux to the synapse. As far as neurotoxicity is concerned, increased reactive oxygen species (ROS production seems to be one of the main causes. Recent research has demonstrated that blockade of a7 nicotinic acetylcholine receptors (nAChR inhibits METH- and MDMA-induced ROS production in striatal synaptosomes which is dependent on calcium and on NO-synthase activation. Moreover, a7 nAChR antagonists (methyllycaconitine and memantine attenuated in vivo the neurotoxicity induced by METH and MDMA, and memantine prevented the cognitive impairment induced by these drugs. Radioligand binding experiments demonstrated that both drugs have affinity to a7 and heteromeric nAChR, with MDMA showing lower Ki values, while fluorescence calcium experiments indicated that MDMA behaves as a partial agonist on a7 and as an antagonist on heteromeric nAChR. Sustained Ca increase led to calpain and caspase-3 activation. In addition, modulatory effects of MDMA on a7 and heteromeric nAChR populations have been found.

  16. Headspace liquid-phase microextraction of methamphetamine and amphetamine in urine by an aqueous drop

    Energy Technology Data Exchange (ETDEWEB)

    He Yi [Department of Sciences, John Jay College of Criminal Justice, City University of New York, 445 W 59th Street, New York, NY 10019 (United States)]. E-mail: yhe@jjay.cuny.edu; Vargas, Angelica [Department of Sciences, John Jay College of Criminal Justice, City University of New York, 445 W 59th Street, New York, NY 10019 (United States); Kang, Youn-Jung [Department of Sciences, John Jay College of Criminal Justice, City University of New York, 445 W 59th Street, New York, NY 10019 (United States)

    2007-04-25

    This study developed a headspace liquid-phase microextraction (LPME) method by using a single aqueous drop in combination with high performance liquid chromatography (HPLC)-UV detection for the determination of methamphetamine (MAP) and amphetamine (AP) in urine samples. The analytes, volatile and basic, were released from sample matrix into the headspace first, and then protonated and dissolved in an aqueous H{sub 3}PO{sub 4} drop hanging in the headspace by a HPLC syringe. After extraction, this drop was directly injected into HPLC. Parameters affecting extraction efficiency were investigated and optimized. This method showed good linearity in the investigated concentration range of 1.0-1500 {mu}g L{sup -1}, repeatability of the extraction (R.S.D. < 5%, n = 6), and low detection limits (0.3 {mu}g L{sup -1} for both analytes). Enrichment factors of about 400-fold and 220-fold were achieved for MAP and AP, respectively, at optimum conditions. The feasibility of the method was demonstrated by analyzing human urine samples.

  17. False-Positive TDxFLx urine Amphetamine/Metamphetamine II assay from Ofloxacin

    International Nuclear Information System (INIS)

    Nomier, Mahmoud A.; Al-Huseini, Hani K.

    2004-01-01

    Immunoassays are widely used in testing urine for illicit drugs. Ofloaxcin and a number of other quinolones were found to induce false-positive opiates (OP) urine immunoassays. This can result in misleading conclusions in the concept of drug abuse The aim of present study was to evaluate the effects of ofloxacin in theraputic doses on the induction of false-positive urine immunoassays for common drugs of abuse in healthy male volunteers. The study was conducted on 6 healthy male volunteers, aging between 35-45 years. Two doses of 400 mg ofloxacin each, were given orally to each volunteer at 12 hours interval and urine samples were collected before ofloaxcin administration and 5-7.5 hours after the second dose. Urine samples were subjected for OP, amphetamine/methamphetamine II (AM/MA II), cocaine and cannabinoids assays on TDxFLx analyzer. Ofloxacin produced significant increase (P cutoff) for AM/MA II assays, were found in all volunteers after ofloaxcin administration. The study recomends strongly the confirmation of positive urine immunoassay results for drugs of abuseby a more specific methodology e.g. gas chromatography/ mass spectroscopy (GC/MS). (author)

  18. 123I-amphetamine-SPECT in the diagnosis of neurological disorders

    International Nuclear Information System (INIS)

    Biersack, H.J.; Kreiten, K.; Hartmann, A.; Friedrich, G.; Linck, H.A.; Winkler, C.; Bonn Univ.; Rheinische Landesklinik, Bonn

    1985-01-01

    In contrast to conventional brain scintigraphy with sup(99m)Tc-pertechnetate, SPECT with 123 I-IMP enables visualization of the brain tissue itself. The relevance of this imaging technique was evaluated in 54 patients with cerebral disorders. SPECT of the brain was performed with a rotating gamma camera. In 6 of 24 epileptic patients, SPECT revealed foci consistent with EEG-findings which were, however, not detected by CCT. In 4 of 25 patients with cerebrovascular disease, hypoperfused areas were detected by SPECT despite negative results obtained with CCT. In 50% (10/20) of the patients with cerebrovascular disease, SPECT showed a greater functional extent of the lesions than CCT. In 3 patients with migraine and normal CCT, regional perfusion disturbancers were found. SPECT with 123 I-labeled amphetamines, therefore, enables diagnosis of functional perfusion disorders and metabolic disturbances that are not revealed by CCT. In addition, SPECT can be used to exactly demonstrate the functional extent of lesions detected by CCT. (orig.) [de

  19. /sup 123/I-amphetamine-SPECT in the diagnosis of neurological disorders

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Kreiten, K.; Hartmann, A.; Friedrich, G.; Linck, H.A.; Winkler, C.

    1985-03-01

    In contrast to conventional brain scintigraphy with sup(99m)Tc-pertechnetate, SPECT with /sup 123/I-IMP enables visualization of the brain tissue itself. The relevance of this imaging technique was evaluated in 54 patients with cerebral disorders. SPECT of the brain was performed with a rotating gamma camera. In 6 of 24 epileptic patients, SPECT revealed foci consistent with EEG-findings which were, however, not detected by CCT. In 4 of 25 patients with cerebrovascular disease, hypoperfused areas were detected by SPECT despite negative results obtained with CCT. In 50% (10/20) of the patients with cerebrovascular disease, SPECT showed a greater functional extent of the lesions than CCT. In 3 patients with migraine and normal CCT, regional perfusion disturbancers were found. SPECT with /sup 123/I-labeled amphetamines, therefore, enables diagnosis of functional perfusion disorders and metabolic disturbances that are not revealed by CCT. In addition, SPECT can be used to exactly demonstrate the functional extent of lesions detected by CCT.

  20. The neuroendocrine response to stress under the effect of drugs: Negative synergy between amphetamine and stressors.

    Science.gov (United States)

    Gómez-Román, Almudena; Ortega-Sánchez, Juan A; Rotllant, David; Gagliano, Humberto; Belda, Xavier; Delgado-Morales, Raúl; Marín-Blasco, Ignacio; Nadal, Roser; Armario, Antonio

    2016-01-01

    There have been numerous studies into the interaction between stress and addictive drugs, yet few have specifically addressed how the organism responds to stress when under the influence of psychostimulants. Thus, we studied the effects of different acute stressors (immobilization, interleukin-1β and forced swimming) in young adult male rats simultaneously exposed to amphetamine (AMPH, 4 mg/kg SC), evaluating classic biological markers. AMPH administration itself augmented the plasma hypothalamic-pituitary-adrenal (HPA) hormones, adrenocorticotropin (ACTH) and corticosterone, without affecting plasma glucose levels. By contrast, this drug dampened the peripheral HPA axis, as well as the response of glucose to the three stressors. We also found that AMPH administration completely blocked the forced swim-induced expression of the corticotropin-releasing hormone (hnCRH) and it partially reduced c-fos expression in the paraventricular nucleus of the hypothalamus (PVN). Indeed, this negative synergy in the forced swim test could even be observed with a lower dose of AMPH (1mg/kg, SC), a dose that is usually received in self-administration experiments. In conclusion, when rats that receive AMPH are subjected to stress, a negative synergy occurs that dampens the prototypic peripheral physiological response to stress and activation of the PVN. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Trends in counterfeits amphetamine-type stimulants after its prohibition in Brazil.

    Science.gov (United States)

    Mariotti, Kristiane de Cássia; Ortiz, Rafael S; Souza, Daniele Z; Mileski, Thayse C; Fröehlich, Pedro E; Limberger, Renata P

    2013-06-10

    Brazil is one of the world's highest users of anorectic drugs, mainly diethylpropione, fenproporex and sibutramine. The present work focuses on physical and chemical characteristics of 17 counterfeited capsules containing amphetamine-type stimulants (ATS) from three seizures conducted by Brazilian Federal Police. The physical profile was useful in indicating forgery, bring complementary information, but the use of this data singly was not sufficient to distinguish between authentic and counterfeited medicines. The chemical analysis revealed that the seizures capsules labeled as Desobesi-M (fenproporex 25mg), actually contained the active pharmaceutical ingrediente (API) sibutramine. The amount of this API ranged from 1/3 to 2 times the amount of drug found in commercial product, may reach twice the recommended daily dose. Multivariate analysis with application of principal component analysis on data from spectroscopy attenuated total reflectance Fourier transform infrared classified the samples according to their similarities, indicating that two seizures had common origin. This study represents the first step in the elucidation of falsification of ATS in Brazil. Considering the forensic intelligence these information are valuable in order to develop and establish a database that enables correlate samples from different locations and/or suppliers and to map the profile and trends of trafficking. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection

    Science.gov (United States)

    Xu, Yun; Zhang, Wenri; Klaus, Judith; Young, Jennifer; Koerner, Ines; Sheldahl, Laird C.; Hurn, Patricia D.; Martínez-Murillo, Francisco; Alkayed, Nabil J.

    2006-09-01

    Estrogen reduces brain injury after experimental cerebral ischemia in part through a genomic mechanism of action. Using DNA microarrays, we analyzed the genomic response of the brain to estradiol, and we identified a transcript, cocaine- and amphetamine-regulated transcript (CART), that is highly induced in the cerebral cortex by estradiol under ischemic conditions. Using in vitro and in vivo models of neural injury, we confirmed and characterized CART mRNA and protein up-regulation by estradiol in surviving neurons, and we demonstrated that i.v. administration of a rat CART peptide is protective against ischemic brain injury in vivo. We further demonstrated binding of cAMP response element (CRE)-binding protein to a CART promoter CRE site in ischemic brain and rapid activation by CART of ERK in primary cultured cortical neurons. The findings suggest that CART is an important player in estrogen-mediated neuroprotection and a potential therapeutic agent for stroke and other neurodegenerative diseases. ischemia | stroke | estrogen

  3. Social support and amphetamine-type stimulant use among female sex workers in China.

    Science.gov (United States)

    Zhao, Qun; Mao, Yuchen; Li, Xiaoming; Zhou, Yuejiao; Shen, Zhiyong

    2017-10-01

    Existing research has suggested a positive role of social support in reducing drug use among female sex workers (FSWs). However, there is limited research on the role of social support in amphetamine-type stimulant (ATS) use among FSWs in China. This study explored the present situation of ATS use among FSWs in Guangxi, China and examined the associations of different types of social support from different sources with ATS use. A sample of 1022 FSWs was recruited from 56 commercial sex venues in Guangxi Autonomous Region in China. Bivariate comparison was used to compare demographic characteristics and source of emotional or tangible social support across frequency of ATS use among FSWs. The relationship between social support and ATS use was examined using multiple ordinal logistic regression models controlling for the potential confounding effects of demographic variables. The multiple ordinal logistic regression indicated that FSWs who were from younger age groups (aOR = 10.88 for age group workers for tangible support (aOR = 1.17). Different types of social support from different sources can be either positively or negatively associated with ATS use among FSWs, therefore, the future intervention efforts should differentiate and target different types and different sources of social support in response to the living and work conditions of FSWs.

  4. Amphetamine-like effects of anorectics and related compounds in pigeons.

    Science.gov (United States)

    Evans, S M; Johanson, C E

    1987-06-01

    Four pigeons were trained to discriminate injections of d-amphetamine (AMPH; 2.0 mg/kg i.m.) from saline with responding maintained under a fixed-ratio 30 schedule of food delivery. When drugs used therapeutically as anorectics were tested, they consistently produced greater than 80% of AMPH-appropriate responding. The order of potency for substituting for AMPH was: mazindol greater than AMPH = phenmetrazine = phentermine greater than chlorphentermine = phendimetrazine = diethylpropion greater than clortermine = mefenorex. Other anorectics such as phenylpropanolamine (0.3-30.0 mg/kg) and fenfluramine (1.0-17.0 mg/kg) only substituted partially for AMPH whereas benzphetamine (1.0-100.0 mg/kg) resulted primarily in saline-appropriate responding. Compounds related to AMPH in biochemical mechanism of action or psychomotor stimulant activity also were tested. Methylphenidate (0.1-3.0 mg/kg), piribedil (0.3-17.0 mg/kg) and nisoxetine (0.03-1.0 mg/kg) shared discriminative stimulus properties with AMPH whereas bupropion (1.0-30.0 mg/kg) and propylhexedrine (10.0-100.0 mg/kg) substituted for AMPH in two of three pigeons tested. In contrast, caffeine and fenetylline resulted principally in saline-appropriate responding. Compounds from pharmacological classes not related to AMPH, such as morphine, diazepam and phencyclidine, failed to substitute for AMPH. In general, compounds with anorectic and/or stimulant properties shared discriminative stimulus properties with AMPH.

  5. Governing through problems: the formulation of policy on amphetamine-type stimulants (ATS) in Australia.

    Science.gov (United States)

    Fraser, Suzanne; Moore, David

    2011-11-01

    Producing and implementing credible and effective policies on illicit drug use is generally seen as an important aspect of health governance in the West. Yet the controversy surrounding illicit drug use means this is no easy task. With public opinion perceived by policy makers to be set against illicit drug use, and understandings of its effects tending towards generalisation and pathologisation, the need for timely and rational responses is considered self evident. These responses are, however, regularly criticised as driven as much by electoral politics and expedience as by research findings or expert opinion. Destined to receive close critical scrutiny from all sides, these policies, and the processes undertaken to develop them, are obliged to negotiate a complex political domain. Despite this scrutiny, and the pressure it brings to bear on the policy-making process, little scholarly attention has been paid to the area to date. In this article, we examine in detail one important area of illicit drug policy - the use of amphetamine-type stimulants (ATS) in Australia. We draw on the international critical literature on the ATS problem to situate our analysis. We note that ideas of 'panic', including Cohen's notion of moral panic, have been used here to good effect, but, aiming to acknowledge the complexities of policy, we turn to poststructuralist methods of policy analysis to pursue a different approach. Following Bacchi's observation that 'we are governed through problematisations rather than policies' (2009, p. xi), we ask how the problem of ATS use has been formulated in policy. We examine key state and national policy documents, and two central themes found in them - causation and evidence - to identify the specific strategies used to authorise the recommendations and measures presented as following from the problem of ATS use. In doing so, we clarify important ways in which policy may at times work to obscure the limits of its legitimacy. Copyright © 2011

  6. Perturbations in different forms of cost/benefit decision making induced by repeated amphetamine exposure.

    Science.gov (United States)

    Floresco, Stan B; Whelan, Jennifer M

    2009-08-01

    Psychostimulant abuse has been linked to impairments in cost-benefit decision making. We assessed the effects of repeated amphetamine (AMPH) treatment in rodents on two distinct forms of decision making. Separate groups of rats were trained for 26 days on either a probabilistic (risk) or effort-discounting task, each consisting of four discrete blocks of ten choice trials. One lever always delivered a smaller reward (one or two pellets), whereas another lever delivered a four-pellet reward. For risk-discounting, the probability of receiving the larger reward decreased across trial blocks (100-12.5%), whereas on the effort task, four pellets could be obtained after a ratio of presses that increased across blocks (2-20). After training, rats received 15 saline or AMPH injections (escalating from 1 to 5 mg/kg) and were then retested during acute and long-term withdrawal. Repeated AMPH administration increased risky choice 2-3 weeks after drug exposure, whereas these treatments did not alter effort-based decision making in a separate group of animals. However, prior AMPH exposure sensitized the effects of acute AMPH on both forms of decision making, whereby lower doses were effective at inducing "risky" and "lazy" patterns of choice. Repeated AMPH exposure leads to relatively long-lasting increases in risky choice, as well as sensitization to the effects of acute AMPH on different forms of cost/benefit decision making. These findings suggest that maladaptive decision-making processes exhibited by psychostimulant abusers may be caused in part by repeated drug exposure.

  7. Interactions of [3H]amphetamine with rat brain synaptosomes. II. Active transport

    International Nuclear Information System (INIS)

    Zaczek, R.; Culp, S.; De Souza, E.B.

    1991-01-01

    The accumulation of 5 nM d-[ 3 H]amphetamine (d-[ 3 H]AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-[ 3 H]AMPH into striatal synaptosomes was saturable, of high affinity, ouabain-sensitive and temperature-dependent, suggesting an active transport phenomenon. Eadee-Hofstee analysis of striatal d-[ 3 H]AMPH transport (AMT) saturation isotherms indicated an apparent Km of 97 nM and a Vmax of 3.0 fmol/mg tissue/min. Lesion of the striatal dopaminergic innervation led to equivalent decreases of [ 3 H] dopamine (DA) transport and AMT, indicating that AMT occurs in DA terminals. Furthermore, AMT was not evident in cerebral cortex, a brain region with a paucity of DA terminals. In competition studies, AMT was stereospecific; d-AMPH (IC50 = 60 nM) was an 8-fold more potent inhibitor of the transport than its I-isomer (IC50 = 466 nM). DA(IC50 = 257 nM), DA uptake blockers and substrates were found to be potent inhibitors of AMT: GBR12909 IC50 = 5 nM; methamphetamine IC50 = 48 nM; methylphenidate IC50 = 53 nM; and cocaine IC50 = 172 nM. In contrast, serotonin was relatively weak in inhibiting AMT (IC50 = 7.9 microM). There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents. AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man. Differences between AMT and d-[ 3 H]AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed

  8. Effect of Amphetamine on Adult Male and Female Rats Prenatally Exposed to Methamphetamine

    Directory of Open Access Journals (Sweden)

    Romana Šlamberová

    2014-01-01

    Full Text Available The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA exposure to adult amphetamine (AMP treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed were administered with AMP (5 mg/kg or saline (1 ml/kg in adulthood. Behaviour in unknown environment was examined in open field test (Laboras, active drug-seeking behaviour in conditioned place preference test (CPP, spatial memory in the Morris water maze (MWM, and levels of corticosterone (CORT were analyzed by enzyme immunoassay (EIA. Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

  9. Methamphetamine and amphetamine concentrations in survivors of body-packer syndrome in Japan.

    Science.gov (United States)

    Uekusa, Kyoko; Hayashida, Makiko; Saito, Nobuyuki; Mashiko, Kunihiro; Hara, Kenji; Waters, Brian; Ohno, Youkichi

    2013-04-10

    There are few reports from Japan on the analysis of fluids in survivors of body-packer syndrome. We analyzed the concentrations of stimulants in the serum, plasma and urine collected from three patients suspected of being body packers at immigration that were referred to hospitals between 2010 and 2011. The drugs were extracted with solid-phase columns and analyzed by gas chromatography-mass spectrometry (GC-MS). In all cases, wrapped, cylindrical packets of foreign bodies were detected in the intestinal tract on plain X-ray (X-P) and computed tomography (CT), and they were eventually removed surgically. In case 1, the patient presented with convulsions and tachycardia at admission to the hospital and one of the packets was found to have ruptured. In case 2, although the subject appeared to have an intestinal obstruction caused by the packets on the third day, he exhibited no symptoms on arrival and the packets did not appear to have ruptured. In case 3, the patient exhibited restlessness on the first day and one of the removed packets had ruptured. In all cases, methamphetamine (MA) and amphetamine (AP) were detected in serum, plasma and urine. In this study, we report the variation in MA and AP concentrations in survivors of body-packer syndrome. The serum and plasma concentrations of MA were high in subjects that exhibited symptoms of MA intoxication. MA and AP were also detected in the case in which the patient exhibited no symptoms of intoxication and the packets had not ruptured. These results suggest either that the stimulants may have seeped through the wrap of the packets, or that the subject had been abusing the drugs. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Maternal and fetal cocaine- and amphetamine-regulated transcript in diabetic and non-diabetic pregnancy.

    LENUS (Irish Health Repository)

    Hehir, Mark P

    2012-09-01

    Cocaine- and amphetamine-regulated transcript (CART) is a leptin-regulated anorectic neuropeptide. Increased levels of leptin in cord blood of diabetic mothers have previously been described. The aim of this study was to quantify maternal and fetal serum CART levels in type 1 diabetes mellitus (T1DM, n = 10) and non-diabetic pregnancy (n = 10). Matched maternal serum samples (n = 20) were obtained at 36-weeks gestation and cord samples from the umbilical vein at delivery (n = 20), CART was quantified using a competitive enzyme immunoassay. Statistical analysis was performed using Spearmans correlation and t test. There was no difference in maternal CART levels at 36-weeks gestation between T1DM (mean = 331.13 pg\\/ml, Standard Error of the Mean (SEM) = 114.54) and non-diabetic pregnancy (mean = 195.01 pg\\/ml SEM = 29.37) (p = 0.106). Fetal CART levels in the umbilical vein were similar in T1DM (mean = 199.27 pg\\/ml, SEM = 39.81) and non-diabetic pregnancy (mean = 149.76 pg\\/ml, SEM = 26.08) (p = 0.143). Maternal serum CART levels measured at 36-weeks gestation correlated with maternal BMI at booking (Spearmans ρ = 0.332) (p = 0.001) irrespective of diabetes. Serum CART can be detected in both diabetic and non-diabetic human pregnancy and may play an important role in body mass regulation in pregnancy.

  11. Nucleus accumbens cocaine-amphetamine regulated transcript mediates food intake during novelty conflict

    Science.gov (United States)

    Burghardt, PR; Krolewski, DM; Dykhuis, KE; Ching, J; Pinawin, AM; Britton, SL; Koch, LG; Watson, SJ; Akil, H.

    2016-01-01

    Obesity is a persistent and pervasive problem, particularly in industrialized nations. It has come to be appreciated that the metabolic health of an individual can influence brain function and subsequent behavioral patterns. To examine the relationship between metabolic phenotype and central systems that regulate behavior, we tested rats with divergent metabolic phenotypes (Low Capacity Runner: LCR vs. High Capacity Runner: HCR) for behavioral responses to the conflict between hunger and environmental novelty using the novelty suppressed feeding (NSF) paradigm. Additionally, we measured expression of mRNA, for peptides involved in energy management, in response to fasting. Following a 24-h fast, LCR rats showed lower latencies to begin eating in a novel environment compared to HCR rats. A 48-h fast equilibrated the latency to begin eating in the novel environment. A 24-h fast differentially affected expression of cocaine-amphetamine regulated transcript (CART) mRNA in the nucleus accumbens (NAc), where 24-h of fasting reduced CART mRNA in LCR rats. Bilateral microinjections of CART 55–102 peptide into the NAc increased the latency to begin eating in the NSF paradigm following a 24-h fast in LCR rats. These results indicate that metabolic phenotype influences how animals cope with the conflict between hunger and novelty, and that these differences are at least partially mediated by CART signaling in the NAc. For individuals with poor metabolic health who have to navigate food-rich and stressful environments, changes in central systems that mediate conflicting drives may feed into the rates of obesity and exacerbate the difficulty individuals have in maintaining weight loss. PMID:26926827

  12. Fenproporex and amphetamine pharmacokinetics in oral fluid after controlled oral administration of fenproporex.

    Science.gov (United States)

    Comiran, Eloisa; Souza, Daniele Zago; Boehl, Paula Otero; Cássia Mariotti, Kristiane de; Pechansky, Flavio; Duarte, Paulina do Carmo Arruda Vieira; De Boni, Raquel Brandini; Fröehlich, Pedro Eduardo; Limberger, Renata Pereira

    2012-10-01

    Fenproporex hydrochloride (FEN) is an anorectic drug used in the treatment of obesity, and its major metabolite is amphetamine (AMP), another central nervous system stimulant. The concentration versus time profile of FEN and its metabolite AMP has been described in classic biological matrices such as plasma and urine; however, there are no reports of such data in oral fluid. The aim of this study is to describe the pharmacokinetics of FEN and AMP in oral fluid after intake of FEN. Twenty-five milligrams of FEN (1 capsule of Desobesi-m) was orally administered to 6 male volunteers, and oral fluid samples were collected with a Quantisal device during 24.00 hours after drug ingestion. These samples were submitted to solid-phase microextraction before analysis by gas chromatography-mass spectrometry in the selected-ion-monitoring mode, using deuterium-labeled AMP as internal standard. After FEN administration, both analytes could be detected in oral fluid of all volunteers with an initial detection time varying from 0.50 to 1.00 hour. FEN peak concentrations occurred between 1.00 and 1.50 hours after administration and were between 70.7 and 227.5 μg/L. For AMP, peak concentration occurred between 1.50 and 4.00 hours, reaching 33.0-150.9 μg/L. The authors observed that oral administration of FEN resulted in significant amounts of FEN and AMP in oral fluid, showing that oral fluid could be a biological matrix suitable for pharmacokinetic studies for both analytes. Using a compartmental approach, FEN data were best fitted by 1-compartment model with first-order input and output, whereas AMP followed a 2-compartment model with first-order input and output.

  13. Amphetamine modulates brain signal variability and working memory in younger and older adults.

    Science.gov (United States)

    Garrett, Douglas D; Nagel, Irene E; Preuschhof, Claudia; Burzynska, Agnieszka Z; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R; Bäckman, Lars; Lindenberger, Ulman

    2015-06-16

    Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD(BOLD)) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.

  14. Use and abuse of amphetamine-type stimulants in the United States of America

    Directory of Open Access Journals (Sweden)

    G. Cajetan Luna

    2001-02-01

    Full Text Available In recent years the United States of America has experienced economic growth, low unemployment, low inflation, and technological advances. However, coexisting with these favorable conditions are underlying and underaddressed social inequalities that may have an impact on patterns of use and abuse of substances, including amphetamine-type stimulants (ATSs. For example, since 1975 most of the increase in national income has benefited people who are at the top 20% of the income range. There are disparities between those who do have and those who do not have the skills needed to thrive in a technologically dependent society, and the gap may be widening. New patterns of substance abuse being seen in the United States may in part be explained by the increasing competition to survive financially and interpersonally, the need that those failing to adapt to rapid technological change have to escape psychologically and existentially, and the desire of the socially alienated and disenfranchised to self-medicate with ATSs and at least temporarily avoid social and economical inequities. According to the 1998 National Household Survey on Drug Abuse, an estimated 13.6 million Americans were users of illicit drugs (1. This number is less than the 13.9 million estimated for 1997, and by comparison less than the highest level, in 1979, when the estimate was 25 million. With respect to stimulants in particular, the overall level of usage has remained constant, but increases have been observed in specific high-risk populations, who need focused outreach and intervention efforts. This article will focus on ATSs in the United States, including relevant demographic and cultural dimensions of their use and abuse, and suggested directions for future ATS research and program development.

  15. Discriminative stimulus properties of intragastrically administered d-amphetamine and pentobarbital in rhesus monkeys.

    Science.gov (United States)

    de la Garza, R; Johanson, C E

    1987-12-01

    Rhesus monkeys were trained to discriminate intragastrically administered d-amphetamine (AMPH) or pentobarbital (PENTO) from saline using a signaled shock-avoidance trail procedure. All monkeys maintained criterion levels (greater than 90% drug-appropriate responding) throughout the duration of the study during training sessions. In the AMPH experiment, the anorectics diethylpropion, mazindol, phendimetrazine, phenmetrazine and phentermine completely substituted for the training dose of AMPH. The atypical antidepressant bupropion and the psychomotor stimulant methylphenidate also completely substituted for AMPH. Other anorectics including benzphetamine, clortermine, fenetylline, mefenorex and the psychomotor stimulant pemoline that share some pharmacological properties with AMPH substituted for AMPH in some, but not all, of the monkeys tested. The anorectics fenfluramine and chlorphentermine failed to substitute for AMPH. Drugs from other pharmacological classes such as morphine, diazepam, nortripyline and PENTO also failed to substitute for AMPH, indicating pharmacological specificity. In the PENTO experiment, the benzodiazepines alprazolam, bromazepam, diazepam, flurazepam, halazepam, lorazepam, midazolam, oxazepam, temazepam and triazolam and the sedatives methaqualone and phenobarbital completely substituted for the training dose of PENTO. The nonbenzodiazepine anxiolytic CL 218,872 only partially substituted for PENTO. In addition, morphine and AMPH failed to substitute for PENTO, indicating pharmacological specificity. In summary, drugs delivered intragastrically functioned as discriminative stimuli in a drug-class specific manner. The ability to use drugs delivered by this route as discriminative stimuli provides a way to compare anorectic drugs to AMPH or sedative drugs to PENTO under conditions that resemble the mode of human consumption to determine whether these drugs are likely to be associated with AMPH-like or PENTO-like drug dependence.

  16. The Effects of Oral d-Amphetamine on Impulsivity in Smoked and Intranasal Cocaine Users

    Science.gov (United States)

    Reed, Stephanie Collins; Evans, Suzette M.

    2016-01-01

    BACKGROUND Effective treatments for cocaine use disorders remain elusive. Two factors that may be related to treatment failures are route of cocaine used and impulsivity. Smoked cocaine users are more likely to have poorer treatment outcomes compared to intranasal cocaine users. Further, cocaine users are impulsive and impulsivity is associated with poor treatment outcomes. While stimulants are used to treat Attention Deficit Hyperactivity Disorder (ADHD) and attenuate certain cocaine-related behaviors, few studies have comprehensively examined whether stimulants can reduce behavioral impulsivity in cocaine users, and none examined route of cocaine use as a factor. METHODS The effects of immediate release oral d-amphetamine (AMPH) were examined in 34 cocaine users (13 intranasal, 21 smoked). Participants had three separate sessions where they were administered AMPH (0, 10, or 20 mg) and completed behavioral measures of impulsivity and risk-taking and subjective measures of abuse liability. RESULTS Smoked cocaine users were more impulsive on the Delayed Memory Task, the GoStop task and the Delay Discounting Task than intranasal cocaine users. Smoked cocaine users also reported more cocaine craving and negative mood than intranasal cocaine users. AMPH produced minimal increases on measures of abuse liability (e.g., Drug Liking). CONCLUSIONS Smoked cocaine users were more impulsive than intranasal cocaine users on measures of impulsivity that had a delay component. Additionally, although AMPH failed to attenuate impulsive responding, there was minimal evidence of abuse liability in cocaine users. These preliminary findings need to be confirmed in larger samples that control for route and duration of cocaine use. PMID:27114203

  17. Determination of amphetamine-type stimulants in oral fluid by solid-phase microextraction and gas chromatography-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Daniele Z., E-mail: daniele.dzs@dpf.gov.br [Setor Tecnico-Cientifico, Superintendencia Regional do Departamento de Policia Federal no Rio Grande do Sul, 1365 Ipiranga Avenue, Azenha, Zip Code 90160-093 Porto Alegre, Rio Grande do Sul (Brazil); Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil); Boehl, Paula O.; Comiran, Eloisa; Mariotti, Kristiane C. [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil); Pechansky, Flavio [Centro de Pesquisa em Alcool e Drogas (CPAD), Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, 2350, Ramiro Barcelos Street, Zip Code 90035-903 Porto Alegre, Rio Grande do Sul (Brazil); Duarte, Paulina C.A.V. [Secretaria Nacional de Politicas sobre Drogas (SENAD), Esplanada dos Ministerios, Block ' A' , 5th floor, Zip Code 70050-907 Brasilia, Distrito Federal (Brazil); De Boni, Raquel [Centro de Pesquisa em Alcool e Drogas (CPAD), Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, 2350, Ramiro Barcelos Street, Zip Code 90035-903 Porto Alegre, Rio Grande do Sul (Brazil); Froehlich, Pedro E.; Limberger, Renata P. [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil)

    2011-06-24

    Graphical abstract: Highlights: > Propylchloroformate derivatization of amphetamine-type stimulants in oral fluid. > Direct immersion solid-phase microextraction/gas chromatography-mass spectrometry. > Linear range 2(4)-256 ng mL{sup -1}, detection limits 0.5-2 ng mL{sup -1}. > Accuracy 98-112%, precision <15% of RSD, recovery 77-112%. > Importance of residual evaluation in checking model goodness-of-fit. - Abstract: A method for the simultaneous identification and quantification of amphetamine (AMP), methamphetamine (MET), fenproporex (FEN), diethylpropion (DIE) and methylphenidate (MPH) in oral fluid collected with Quantisal{sup TM} device has been developed and validated. Thereunto, in-matrix propylchloroformate derivatization followed by direct immersion solid-phase microextraction and gas chromatography-mass spectrometry were employed. Deuterium labeled AMP was used as internal standard for all the stimulants and analysis was performed using the selected ion monitoring mode. The detector response was linear for the studied drugs in the concentration range of 2-256 ng mL{sup -1} (neat oral fluid), except for FEN, whereas the linear range was 4-256 ng mL{sup -1}. The detection limits were 0.5 ng mL{sup -1} (MET), 1 ng mL{sup -1} (MPH) and 2 ng mL{sup -1} (DIE, AMP, FEN), respectively. Accuracy of quality control samples remained within 98.2-111.9% of the target concentrations, while precision has not exceeded 15% of the relative standard deviation. Recoveries with Quantisal{sup TM} device ranged from 77.2% to 112.1%. Also, the goodness-of-fit concerning the ordinary least squares model in the statistical inference of data has been tested through residual plotting and ANOVA. The validated method can be easily automated and then used for screening and confirmation of amphetamine-type stimulants in drivers' oral fluid.

  18. Object recognition impairment in Fmr1 knockout mice is reversed by amphetamine: involvement of dopamine in the medial prefrontal cortex.

    Science.gov (United States)

    Ventura, R; Pascucci, T; Catania, M V; Musumeci, S A; Puglisi-Allegra, S

    2004-09-01

    Fragile X syndrome is an X-linked form of mental retardation including, among others, symptoms such as stereotypic behaviour, hyperactivity, hyperarousal, and cognitive deficits. We hypothesized that hyperactivity and/or compromised attentional, cognitive functions may lead to impaired performance in cognitive tasks in Fmr1 knockout mice, the most widely used animal model of fragile X syndrome, and suggested that psychostimulant treatment may improve performance by acting on one or both components. Since hyperactivity and cognitive functions have been suggested to depend on striatal and prefrontal cortex dopaminergic dysfunction, we assessed whether amphetamine produced beneficial, positive effects by acting on dopaminergic corticostriatal systems. Our results show that Fmr1 knockout mice are not able to discriminate between a familiar object and a novel one in the object recognition test, thus showing a clear-cut cognitive impairment that, to date, has been difficult to demonstrate in other cognitive tasks. Amphetamine improved performance of Fmr1 knockout mice, leading to enhanced ability to discriminate novel versus familiar objects, without significantly affecting locomotor activity. In agreement with behavioural data, amphetamine produced a greater increase in dopamine release in the prefrontal cortex of Fmr1 knockout compared with the wild-type mice, while a weak striatal dopaminergic response was observed in Fmr1 knockout mice. Our data support the view that the psychostimulant ameliorates performance in Fmr1 knockout mice by improving merely cognitive functions through its action on prefrontal cortical dopamine, irrespective of its action on motor hyperactivity. These results indicate that prefrontal cortical dopamine plays a major role in cognitive impairments characterizing Fmr1 knockout mice, thus pointing to an important aetiological factor in the fragile X syndrome.

  19. Scopolamine and amphetamine produce similar decision-making deficits on a rat gambling task via independent pathways.

    Science.gov (United States)

    Silveira, Mason M; Malcolm, Emma; Shoaib, Mohammed; Winstanley, Catharine A

    2015-03-15

    Disorders characterized by disturbed cholinergic signaling, such as schizophrenia, exhibit impaired performance on measures of real-world cost/benefit decision-making. Whether the cholinergic system contributes to the choice deficits observed is currently unknown. We therefore determined the effects of broad-acting agonists and antagonists at the nicotinic and muscarinic receptor on decision making, as measured by the rodent gambling task (rGT). Given the anatomical and functional connectivity of the cholinergic and dopaminergic systems, we also sought to modulate amphetamine's previously reported effect on rGT performance via the cholinergic system. Male rats were trained on the rGT, during which animals chose from four different options. The optimal strategy on the rGT is to favor options associated with smaller immediate rewards and less punishment/loss. Impulsive action was also measured by recording the number of premature responses made. Performance on the rGT was assessed following acute treatment with the muscarinic receptor agonist oxotremorine, the muscarinic receptor antagonist scopolamine, nicotine, and the nicotinic receptor antagonist mecamylamine. Similar to the effect produced by amphetamine, muscarinic receptor antagonism with scopolamine (0.1mg/kg) impaired decision making, albeit to a lesser degree. Prior muscarinic agonism with oxotremorine was unable to attenuate amphetamine's effects on rGT performance. Oxotremorine, nicotine, and mecamylamine did not affect the choice profile. We therefore conclude that modulation of the muscarinic, but not nicotinic, receptor system can affect decision making under conditions of risk and uncertainty. Such findings contribute to a broader understanding of the cognitive deficits observed in disorders in which cholinergic signaling is compromised. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. [Application of hair analysis of selected psychoactive substances for medico-legal purposes. Part II. Cases of complex fatal poisonings: interactions of heroine - cocaine - amphetamines].

    Science.gov (United States)

    Rojek, Sebastian; Kłys, Małgorzata; Rzepecka-Woźniak, Ewa; Konopka, Tomasz

    2010-01-01

    The study represents an attempt at employing segmental hair analysis in complex poisonings with xenobiotic mixtures of heroine - cocaine - amphetamines in the context of the cause of death as a consequence of complex interaction mechanisms which occurred prior to death. Two cases of complex poisonings: heroine - cocaine and heroine - cocaine - amphetamines were analyzed and documented with macro- and microscopic examinations and complex toxicological examinations, including the analysis of classic biological material, i.e. samples of selective blood, and alternative material, i.e. hair samples. Determinations of opioids, cocaine and its metabolite and amphetamines in the hair biological matrix were performed using high performance liquid chromatography--atmospheric pressure chemical ionization--tandem mass spectrometry (HPLC-APCI-MS-MS). Segmental hair analysis of the investigated cases indicated a prolonged intake of similar psychoactive substances and a developed adaptation of the addicted to interaction mechanisms, which, however, led gradually to multiorgan anatomopathological changes, and in consequence to death.

  1. Novel Selectivity-Based Forensic Toxicological Validation of a Paper Spray Mass Spectrometry Method for the Quantitative Determination of Eight Amphetamines in Whole Blood

    Science.gov (United States)

    Teunissen, Sebastiaan F.; Fedick, Patrick W.; Berendsen, Bjorn J. A.; Nielen, Michel W. F.; Eberlin, Marcos N.; Graham Cooks, R.; van Asten, Arian C.

    2017-12-01

    Paper spray tandem mass spectrometry is used to identify and quantify eight individual amphetamines in whole blood in 1.3 min. The method has been optimized and fully validated according to forensic toxicology guidelines, for the quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy- N-methylamphetamine (MDMA), 3,4-methylenedioxy- N-ethylamphetamine (MDEA), para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA), and 4-fluoroamphetamine (4-FA). Additionally, a new concept of intrinsic and application-based selectivity is discussed, featuring increased confidence in the power to discriminate the amphetamines from other chemically similar compounds when applying an ambient mass spectrometric method without chromatographic separation. Accuracy was within ±15% and average precision was better than 15%, and better than 20% at the LLOQ. Detection limits between 15 and 50 ng/mL were obtained using only 12 μL of whole blood. [Figure not available: see fulltext.

  2. An unusual presentation of a customs importation seizure containing amphetamine, possibly synthesized by the APAAN-P2P-Leuckart route.

    Science.gov (United States)

    Power, John D; Barry, Michael G; Scott, Kenneth R; Kavanagh, Pierce V

    2014-01-01

    During the analysis of an Irish customs seizure (14 packages each containing approximately one kilogram of a white wet paste) were analysed for the suspected presence of controlled drugs. The samples were found to contain amphetamine and also characteristic by-products including benzyl cyanide, phenylacetone (P2P), methyl-phenyl-pyrimidines, N-formylamphetamine, naphthalene derivatives and amphetamine dimers. The analytical results corresponded with the impurity profile observed and recently reported for the synthesis of 4-methylamphetamine from 4-methylphenylacetoacetonitrile [1]. The synthesis of amphetamine from alpha-phenylacetoacetonitrile (APAAN) was performed (via an acid hydrolysis and subsequent Leuckart reaction) and the impurity profile of the product obtained was compared to those observed in the customs seizure. Observations are made regarding the route specificity of these by-products. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Mortality and causes of death among people who inject amphetamine: A long-term follow-up cohort study from a needle exchange program in Sweden.

    Science.gov (United States)

    Åhman, Ada; Jerkeman, Anna; Blomé, Marianne Alanko; Björkman, Per; Håkansson, Anders

    2018-07-01

    Abuse of amphetamines is a worldwide problem with around 34 million users, and amphetamine is commonly used by people who inject drugs (PWID). Despite this, there is relatively little research on mortality and cause of death among people who use amphetamines primarily. The present study aimed to examine mortality and causes of death among people who inject amphetamine, and compare these results to the general population. This retrospective cohort study was based on data from The Malmö Needle Exchange Program in Sweden (MNEP) and on data from The Swedish National Cause of Death Register. Participants in the MNEP, between 1987 and 2011, with registered national identity number and amphetamine as their primary drug of injection use, were included in the study. Standardized mortality ratios (SMR) was calculated for overall mortality and categories of causes of death. 2019 individuals were included (mean follow-up-time 13.7 years [range 0.02-24.2 years], a total of 27,698 person-years). Of the 448 deceased, 428 had a registered cause of death. The most common causes of death were external causes (n = 162, 38%), followed by diseases of the circulatory system (n = 67, 16%). SMR were significantly elevated (8.3, 95% CI [7.5-9.1]) for the entire study population, and for every category of causes of death respectively. People injecting amphetamine as a primary drug were found to have significantly elevated mortality compared with the general population, with high rates of both external and somatic causes of death. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Effects of 21-day d-amphetamine and risperidone treatment on cocaine vs food choice and extended-access cocaine intake in male rhesus monkeys.

    Science.gov (United States)

    Hutsell, Blake A; Negus, S Stevens; Banks, Matthew L

    2016-11-01

    Clinical trial data suggest amphetamine treatment is most efficacious in moderate to high frequency cocaine users. However, preclinical studies have examined amphetamine treatment effects under relatively limited cocaine access conditions with low to moderate cocaine intakes. This study determined d-amphetamine treatment effects on cocaine self-administration in rhesus monkeys under cocaine access conditions allowing for high daily cocaine intake. For comparison and as a negative control, treatment effects with the antipsychotic risperidone were also examined. Continuous 21-day treatments with ramping doses of d-amphetamine (days 1-7: 0.032mg/kg/h; days 8-21: 0.1mg/kg/h, i.v.) or risperidone (days 1-7: 0.001mg/kg/h; days 8-14: 0.0032mg/kg/h; days 15-21: 0.0056mg/kg/h, i.v.) were administered to rhesus monkeys (n=4) with daily access to two types of cocaine self-administration sessions: (1) a 2-h 'choice' session with concurrent availability of 1-g food pellets and intravenous cocaine injections (0-0.1mg/kg per injection) and (2) a 20-h 'extended-access' session with 0.1mg/kg per injection cocaine availability. Total daily cocaine intake increased >6-fold during extended cocaine access. d-Amphetamine significantly decreased total cocaine intake, but not cocaine vs food choice. In contrast, risperidone did not significantly alter either total cocaine intake or cocaine vs. food choice. These results confirm and extend previous results supporting treatment effectiveness for monoamine releasers, but not dopamine antagonists, to reduce cocaine self-administration. Moreover, these results suggest amphetamine treatment efficacy to decrease preclinical cocaine vs. food choice may depend upon cocaine access conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Comparison of the efficacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced deficits in a reversal learning task in the rat

    Directory of Open Access Journals (Sweden)

    Nagi F Idris

    2009-06-01

    Full Text Available Recent studies in our laboratory have shown that PCP (phencyclidine and d-amphetamine induce a cognitive deficit in rats, in a paradigm of potential relevance for the pathology of schizophrenia. Atypical, but not classical antipsychotics and the anticonvulsant, lamotrigine have been shown to prevent a selective reversal learning deficit induced by PCP. In contrast, only haloperidol reversed the d-amphetamine-induced deficit. The present study aimed to explore the ability of two anticonvulsants with differing mechanism of action, valproate and phenytoin to attenuate the cognitive deficits induced by PCP and d-amphetamine in the reversal learning paradigm. PCP at 1.5mg/kg and d-amphetamine at 0.5mg/kg both produced a selective and significant reduction in performance of the reversal phase with no effect on the initial phase of the task in female-hooded Lister rats. Valproate (25-200mg/kg and phenytoin (25-50mg/kg had no effect on performance when administered alone. Valproate (100-200mg/kg, whose principle action is thought to be the enhancement of GABA transmission, was unable to prevent the cognitive deficit induced by either PCP or d-amphetamine. Conversely, phenytoin (50mg/kg, a use-dependent sodium channel inhibitor, significantly prevented the deficit induced by PCP, but not d-amphetamine. These results add to our earlier work with lamotrigine, and suggest that sodium channel blockade may be a mechanism by which some anticonvulsant drugs can prevent the PCP-induced deficit. These data have implications for the use of anticonvulsant drugs in the treatment of cognitive or psychotic disorders.

  6. Amphetamine-type stimulant use and the risk of injury or death as a result of a road-traffic accident: A systematic review of observational studies.

    Science.gov (United States)

    Hayley, Amie C; Downey, Luke A; Shiferaw, Brook; Stough, Con

    2016-06-01

    Amphetamine-type substances are frequently detected among drivers injured or killed due to road-trauma. However, the role of this substance in crash causation remains equivocal. We performed a systematic review to evaluate existing evidence regarding the association between amphetamine use and the risk of injury or death due to road traffic accidents. A bibliographical search of PubMed, SafetyLit, Scopus, and Science Direct literature databases from 01 January 1980 until May 2015 was performed. The quality of included studies was assessed using the Newcastle-Ottowa Scale (NOS) (cut-off of ≥7 indicated high quality). Inter-rater reliability between three independent reviewers for the NOS was calculated using Cohens kappa (κ) statistic, and best-evidence synthesis was performed. A total of 182 articles were found. Nine studies met eligibility criteria for inclusion for review, and seven studies were included for best-evidence synthesis. Best-evidence synthesis demonstrated a conflicting level of evidence for associations between the use of-amphetamine-type substances and the risk of sustaining an injury, and a moderate level of evidence between amphetamine use and the risk of death due to road trauma. This is the first review to synthesise evidence regarding the association between amphetamine-type substance use and the risk of injury or death due to a road traffic accident. More conclusive evidence of death due to road trauma among amphetamine users may reflect significant and global deficits in functioning associated with effective vehicular control under the influence of this substance. Additional high quality, sufficiently powered studies are required to elucidate the magnitude of these associations. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  7. Amphetamines analysis in wastewaters - method performance of solid phase extraction - higher performance liquid chromatography mass spectrometry techniques (SPE-HPLC MS/MS)

    Science.gov (United States)

    Mustapha, Aliru Olajide; Ajao, Usman L

    2011-01-01

    Recently, many articles have reported different levels and distribution of amphetamine hitherto detected in biological fluids now appreciably found in aquatic environment at ng/L levels. Identification and measurement of amphetamine and its metabolites in surface and sewage waters using higher performance liquid chromatographic methodologies in the literatures now on current trend have provided information that are of scientific interest and effectively replaced immunological methods which only suggest the presence of these substances. Active research on both distribution and impacts of this important drug of abuse and related metabolites in the wastewaters are on-going. PMID:27857670

  8. Ghrelin receptor antagonism attenuates cocaine- and amphetamine-induced locomotor stimulation, accumbal dopamine release, and conditioned place preference.

    Science.gov (United States)

    Jerlhag, Elisabet; Egecioglu, Emil; Dickson, Suzanne L; Engel, Jörgen A

    2010-09-01

    Recently we demonstrated that genetic or pharmacological suppression of the central ghrelin signaling system, involving the growth hormone secretagogue receptor 1A (GHS-R1A), lead to a reduced reward profile from alcohol. As the target circuits for ghrelin in the brain include a mesolimbic reward pathway that is intimately associated with reward-seeking behaviour, we sought to determine whether the central ghrelin signaling system is required for reward from drugs of abuse other than alcohol, namely cocaine or amphetamine. We found that amphetamine-as well as cocaine-induced locomotor stimulation and accumbal dopamine release were reduced in mice treated with a GHS-R1A antagonist. Moreover, the ability of these drugs to condition a place preference was also attenuated by the GHS-R1A antagonist. Thus GHS-R1A appears to be required not only for alcohol-induced reward, but also for reward induced by psychostimulant drugs. Our data suggest that the central ghrelin signaling system constitutes a novel potential target for treatment of addictive behaviours such as drug dependence.

  9. The use of a gold electrode for the determination of amphetamine derivatives and application to their analysis in human urine

    Directory of Open Access Journals (Sweden)

    Nevešćanin Marina M.

    2013-01-01

    Full Text Available The catalytic abilities of gold electrode were tested for the quantitative determination of amphetamine (A and 3,4-methylenedioxy-N-methylamphetamine (MDMA standards by their oxidation using cyclic voltammetry (CV. The value of the oxidative currents of A and MDMA standards at 0.80 V vs. SCE in 0.05 M NaHCO3 at the scan rate of 50 mV/s is linear function of concentration in range of 110.9-258.9 mM and 38.7-229.2 mM, respectively. Square wave voltammetry (SWV revealed linear increase of current with concentration of MDMA (range 30.9-91.6 mM and thus quantitative determination of amphetamine derivates. SWV analysis is successfully performed in spiked urine samples as well. A and MDMA in the presence of sucrose and as a content in illegally produced tablets were also analyzed. The voltammetric determination of A and MDMA derivatives using CV and SWV at gold electrode is a rapid, selective and simple procedure and its accuracy was confirmed with reference method, high performance liquid chromatography (HPLC. The spiked urine samples analysis offers additional possibility for the rapid detection of A and MDMA in human urine.

  10. Relationship between vomiting and taste aversion learning in the ferret: studies with ionizing radiation, lithium chloride, and amphetamine.

    Science.gov (United States)

    Rabin, B M; Hunt, W A

    1992-09-01

    The relationship between emesis and taste aversion learning was studied in ferrets (Mustela putorius furo) following exposure to ionizing radiation (50-200 cGy) or injection of lithium chloride (1.5-3.0 mEq/kg, ip). When 10% sucrose or 0.1% saccharin was used as the conditioned stimulus, neither unconditioned stimulus produced a taste aversion, even when vomiting was produced by the stimulus (Experiments 1 and 2). When a canned cat food was used as the conditioned stimulus, lithium chloride, but not ionizing radiation, produced a taste aversion (Experiment 3). Lithium chloride was effective in producing a conditioned taste aversion when administration of the toxin was delayed by up to 90 min following the ingestion of the canned cat food, indicating that the ferrets are capable of showing long-delay learning (Experiment 4). Experiment 5 examined the capacity of amphetamine, which is a qualitatively different stimulus than lithium chloride or ionizing radiation, to produce taste aversion learning in rats and cats as well as in ferrets. Injection of amphetamine (3 mg/kg, ip) produced a taste aversion in rats and cats but not in ferrets which required a higher dose (> 5 mg/kg). The results of these experiments are interpreted as indicating that, at least for the ferret, there is no necessary relationship between toxin-induced illness and the acquisition of a CTA and that gastrointestinal distress is not a sufficient condition for CTA learning.

  11. Direct Analysis of Amphetamine Stimulants in a Whole Urine Sample by Atmospheric Solids Analysis Probe Tandem Mass Spectrometry

    Science.gov (United States)

    Crevelin, Eduardo J.; Salami, Fernanda H.; Alves, Marcela N. R.; De Martinis, Bruno S.; Crotti, Antônio E. M.; Moraes, Luiz A. B.

    2016-05-01

    Amphetamine-type stimulants (ATS) are among illicit stimulant drugs that are most often used worldwide. A major challenge is to develop a fast and efficient methodology involving minimal sample preparation to analyze ATS in biological fluids. In this study, a urine pool solution containing amphetamine, methamphetamine, ephedrine, sibutramine, and fenfluramine at concentrations ranging from 0.5 pg/mL to 100 ng/mL was prepared and analyzed by atmospheric solids analysis probe tandem mass spectrometry (ASAP-MS/MS) and multiple reaction monitoring (MRM). A urine sample and saliva collected from a volunteer contributor (V1) were also analyzed. The limit of detection of the tested compounds ranged between 0.002 and 0.4 ng/mL in urine samples; the signal-to-noise ratio was 5. These results demonstrated that the ASAP-MS/MS methodology is applicable for the fast detection of ATS in urine samples with great sensitivity and specificity, without the need for cleanup, preconcentration, or chromatographic separation. Thus ASAP-MS/MS could potentially be used in clinical and forensic toxicology applications.

  12. Determination of amphetamine-type stimulants in oral fluid by solid-phase microextraction and gas chromatography-mass spectrometry.

    Science.gov (United States)

    Souza, Daniele Z; Boehl, Paula O; Comiran, Eloisa; Mariotti, Kristiane C; Pechansky, Flavio; Duarte, Paulina C A V; De Boni, Raquel; Froehlich, Pedro E; Limberger, Renata P

    2011-06-24

    A method for the simultaneous identification and quantification of amphetamine (AMP), methamphetamine (MET), fenproporex (FEN), diethylpropion (DIE) and methylphenidate (MPH) in oral fluid collected with Quantisal™ device has been developed and validated. Thereunto, in-matrix propylchloroformate derivatization followed by direct immersion solid-phase microextraction and gas chromatography-mass spectrometry were employed. Deuterium labeled AMP was used as internal standard for all the stimulants and analysis was performed using the selected ion monitoring mode. The detector response was linear for the studied drugs in the concentration range of 2-256 ng mL(-1) (neat oral fluid), except for FEN, whereas the linear range was 4-256 ng mL(-1). The detection limits were 0.5 ng mL(-1) (MET), 1 ng mL(-1) (MPH) and 2 ng mL(-1) (DIE, AMP, FEN), respectively. Accuracy of quality control samples remained within 98.2-111.9% of the target concentrations, while precision has not exceeded 15% of the relative standard deviation. Recoveries with Quantisal™ device ranged from 77.2% to 112.1%. Also, the goodness-of-fit concerning the ordinary least squares model in the statistical inference of data has been tested through residual plotting and ANOVA. The validated method can be easily automated and then used for screening and confirmation of amphetamine-type stimulants in drivers' oral fluid. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Simultaneous analysis of amphetamine-type stimulants in plasma by solid-phase microextraction and gas chromatography-mass spectrometry.

    Science.gov (United States)

    Mariotti, Kristiane de Cássia; Schuh, Roselena S; Ferranti, Priscila; Ortiz, Rafael S; Souza, Daniele Z; Pechansky, Flavio; Froehlich, Pedro E; Limberger, Renata P

    2014-09-01

    Brazil is considered one of the countries with the highest number of amphetamine-type stimulant (ATS) users worldwide, mainly diethylpropion (DIE) and fenproporex (FEN). The use of ATS is mostly linked to diverted prescription stimulants and this misuse is widely associated with (ab)use by drivers. A validated method was developed for the simultaneous analysis of amphetamine (AMP), DIE and FEN in plasma samples employing direct immersion-solid-phase microextraction, and gas chromatographic/mass spectrometric analysis. Trichloroacetic acid 10% was used for plasma deproteinization. In situ derivatization with propylchloroformate was employed. The linear range of the method covered from 5.0 to 100 ng/mL. The detection limits were 1.0 (AMP), 1.5 (DIE) and 2.0 ng/mL (FEN). The accuracy assessment of the control samples was within 85.58-108.33% of the target plasma concentrations. Recoveries ranged from 46.35 to 84.46% and precision was <15% of the value of relative standard deviation. This method is appropriate for screening and confirmation in plasma forensic toxicology analyses of these basic drugs. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. The effects of price and perceived quality on the behavioural economics of alcohol, amphetamine, cannabis, cocaine, and ecstasy purchases.

    Science.gov (United States)

    Goudie, Andrew J; Sumnall, Harry R; Field, Matt; Clayton, Hannah; Cole, Jon C

    2007-07-10

    Behavioural economic models of substance use describe the relationship between changes in unit price and consumption. However, these models rarely take account of the perceived quality (i.e. potency) of controlled drugs. Therefore we investigated the effects of both price and quality on the decision to purchase controlled drugs by polysubstance misusers. Forty current polysubstance misusers (29 males, 11 females; mean age 23.8) were recruited into the study. Participants were asked to hypothetically purchase drugs from a price list of alcohol, amphetamine, cannabis, cocaine and ecstasy at different levels of quality and price (i.e. better quality drugs cost more money). The disposable income available for those purchases was systematically varied in order to determine the impact of income on the decision to purchase drugs. Demand for both normal and strong alcohol was income inelastic. Demand for both poor and average quality cannabis and ecstasy was income inelastic, but demand for good quality cannabis and ecstasy was income elastic. The demand for poor quality cocaine was income inelastic, with the demand for both average and good quality cocaine being income elastic. Participants reported too few purchases of amphetamine, which precluded behavioural economic analysis. These results suggest that, like other goods, controlled drugs are purchased based upon the consumer's interpretations of their relative value. Therefore, it is probable that the purchase and subsequent use of controlled drugs by polysubstance misusers will be heavily influenced by the economic environment.

  15. Interaction of organic cation transporter 3 (SLC22A3) and amphetamine.

    Science.gov (United States)

    Zhu, Hao-Jie; Appel, David I; Gründemann, Dirk; Markowitz, John S

    2010-07-01

    The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission. Relative to wild-type (WT) animals, Oct3 knockout (KO) mice have displayed altered behavioral and neurochemical responses to psychostimulants such as amphetamine (AMPH) and methamphetamine. In the present study, both in vitro and in vivo approaches were utilized to explore potential mechanisms underlying the disparate neuropharmacological effects observed following AMPH exposure in Oct3 KO mice. In vitro uptake studies conducted in OCT3 transfected cells indicated that dextroamphetamine (d-AMPH) is not a substrate of OCT3. However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT). Inhibition studies demonstrated that d-AMPH exerts relatively weak inhibitory effects on the OCT3-mediated uptake of DA, NE, 5-HT, and the model OCT3 substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide. The IC(50) values were determined to be 41.5 +/- 7.5 and 24.1 +/- 7.0 microM for inhibiting DA and 5-HT uptake, respectively, while 50% inhibition of NE and 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide uptake was not achieved by even the highest concentration of d-AMPH applied (100 microM). Furthermore, the disposition of d-AMPH in various tissues including the brain, liver, heart, kidney, muscle, intestine, spleen, testis, uterus, and plasma were determined in both male and female Oct3 KO and WT mice. No significant difference was observed between either genotypes or sex in all tested organs and tissues. Our findings suggest that OCT3 is not a prominent factor influencing the disposition of d-AMPH. Additionally, based upon the inhibitory potency observed in vitro, d

  16. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

    Science.gov (United States)

    Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

    2012-10-25

    Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

  17. Sex-specific differences in the dynamics of cocaine- and amphetamine-regulated transcript and nesfatin-1 expressions in the midbrain of depressed suicide victims vs. controls.

    NARCIS (Netherlands)

    Bloem, B.R.; Xu, L.; Morava, E.; Faludi, G.; Palkovits, M.; Roubos, E.W.; Kozicz, L.T.

    2012-01-01

    An intriguing novel pathophysiological insight into mood disorders is the notion that one's metabolic status influences mood. In rodents, cocaine- and amphetamine-regulated transcript (CART) and nesfatin-1/NUCB2 have not only been implicated in metabolism, but in the pathobiology of anxiety and

  18. Stress-induced locomotor sensitization to amphetamine in adult, but not in adolescent rats, is associated with increased expression of ΔFosB in the nucleus accumbens.

    Directory of Open Access Journals (Sweden)

    Paulo Eduardo Carneiro de Oliveira

    2016-09-01

    Full Text Available While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively were restrained for 2 hours once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p. and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats.

  19. Amphetamine-type stimulant use among men who have sex with men (MSM) in Vietnam : Results from a socio-ecological, community-based study

    NARCIS (Netherlands)

    Vu, Nga Thi Thu; Holt, Martin; Phan, Huong Thi Thu; Le, Huong Thi; La, Lan Thi; Tran, Gioi Minh; Doan, Tung Thanh; Nguyen, Trang Nhu Nguyen; de Wit, John

    2016-01-01

    INTRODUCTION: Amphetamine-type-stimulants (ATS) use is associated with HIV-related sexual risk behaviours and is an emergent problem among men who have sex with men (MSM) in Vietnam. The purpose of this study is to describe ATS use patterns and understand the correlates of recent methamphetamine use

  20. Reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely hospitalized elderly medical patients

    DEFF Research Database (Denmark)

    Glintborg, B.; Olsen, L.; Poulsen, H.

    2008-01-01

    Undisclosed use of illicit drugs and prescription controlled substances is frequent in some settings. The aim of the present study was to estimate the reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely...

  1. Differential effects of stress and amphetamine administration on Fos-like protein expression in corticotropin releasing factor-neurons of the rat brain.

    Science.gov (United States)

    Rotllant, David; Nadal, Roser; Armario, Antonio

    2007-05-01

    Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine.

  2. Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor.

    Science.gov (United States)

    Bunzow, J R; Sonders, M S; Arttamangkul, S; Harrison, L M; Zhang, G; Quigley, D I; Darland, T; Suchland, K L; Pasumamula, S; Kennedy, J L; Olson, S B; Magenis, R E; Amara, S G; Grandy, D K

    2001-12-01

    The trace amine para-tyramine is structurally and functionally related to the amphetamines and the biogenic amine neurotransmitters. It is currently thought that the biological activities elicited by trace amines such as p-tyramine and the psychostimulant amphetamines are manifestations of their ability to inhibit the clearance of extracellular transmitter and/or stimulate the efflux of transmitter from intracellular stores. Here we report the discovery and pharmacological characterization of a rat G protein-coupled receptor that stimulates the production of cAMP when exposed to the trace amines p-tyramine, beta-phenethylamine, tryptamine, and octopamine. An extensive pharmacological survey revealed that psychostimulant and hallucinogenic amphetamines, numerous ergoline derivatives, adrenergic ligands, and 3-methylated metabolites of the catecholamine neurotransmitters are also good agonists at the rat trace amine receptor 1 (rTAR1). These results suggest that the trace amines and catecholamine metabolites may serve as the endogenous ligands of a novel intercellular signaling system found widely throughout the vertebrate brain and periphery. Furthermore, the discovery that amphetamines, including 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"), are potent rTAR1 agonists suggests that the effects of these widely used drugs may be mediated in part by this receptor as well as their previously characterized targets, the neurotransmitter transporter proteins.

  3. Amphetamine sensitization in mice is sufficient to produce both manic- and depressive-related behaviors as well as changes in the functional connectivity of corticolimbic structures.

    Science.gov (United States)

    Pathak, G; Ibrahim, B A; McCarthy, S A; Baker, K; Kelly, M P

    2015-08-01

    It has been suggested that amphetamine abuse and withdrawal mimics the diverse nature of bipolar disorder symptomatology in humans. Here, we determined if a single paradigm of amphetamine sensitization would be sufficient to produce both manic- and depressive-related behaviors in mice. CD-1 mice were subcutaneously dosed for 5 days with 1.8 mg/kg d-amphetamine or vehicle. On days 6-31 of withdrawal, amphetamine-sensitized (AS) mice were compared to vehicle-treated (VT) mice on a range of behavioral and biochemical endpoints. AS mice demonstrated reliable mania- and depression-related behaviors from day 7 to day 28 of withdrawal. Relative to VT mice, AS mice exhibited long-lasting mania-like hyperactivity following either an acute 30-min restraint stress or a low-dose 1 mg/kg d-amphetamine challenge, which was attenuated by the mood-stabilizers lithium and quetiapine. In absence of any challenge, AS mice showed anhedonia-like decreases in sucrose preference and depression-like impairments in the off-line consolidation of motor memory, as reflected by the lack of spontaneous improvement across days of training on the rotarod. AS mice also demonstrated a functional impairment in nest building, an ethologically-relevant activity of daily living. Western blot analyses revealed a significant increase in methylation of histone 3 at lysine 9 (H3K9), but not lysine 4 (H3K4), in hippocampus of AS mice relative to VT mice. In situ hybridization for the immediate-early gene activity-regulated cytoskeleton-associated protein (Arc) further revealed heightened activation of corticolimbic structures, decreased functional connectivity between frontal cortex and striatum, and increased functional connectivity between the amygdala and hippocampus of AS mice. The effects of amphetamine sensitization were blunted in C57BL/6J mice relative to CD-1 mice. These results show that a single amphetamine sensitization protocol is sufficient to produce behavioral, functional, and biochemical

  4. Persistence of drug use during imprisonment: relationship of drug type, recency of use and severity of dependence to use of heroin, cocaine and amphetamine in prison.

    Science.gov (United States)

    Strang, John; Gossop, Michael; Heuston, Joan; Green, John; Whiteley, Christopher; Maden, Anthony

    2006-08-01

    To investigate the persistence of use of heroin, cocaine and amphetamine drugs during imprisonment, and to identify factors associated with increased levels of persistence. The use of heroin, cocaine and amphetamine by current prison inmates has been examined and, in particular, the relationship between drug use within prison and the type of drug used prior to imprisonment, recency of use and severity of dependence. A randomly selected sample of 1009 adult male prisoners in 13 prisons in England and Wales during 1994/95; structured confidential interviews conducted by independent research staff. Enquiry about prior use of heroin, cocaine or amphetamine focused on three time-periods (ever, last year and last month pre-prison) and the use of these drugs during the first month of imprisonment. A total of 557 (55%) of the 1009 prisoners had used previously one of the three drugs selected for study: 58% had used heroin, 69% cocaine and 75% amphetamine. More than half (59%; 327/557) had used these drugs in the month before the current imprisonment. Drug use in prisons was most likely to occur among those who had used in the month prior to imprisonment. The persistence of heroin use in prison occurred more frequently (70%) than use of cocaine (20%) or amphetamine (15%). Of those using heroin pre-imprisonment, 67% considered they were dependent, compared to 15% and 22%, respectively, for cocaine and amphetamine users. Changes in the drug-taking behaviour of drug users after imprisonment vary according to the type of drug being taken. Prisoners were much more likely to continue to use heroin than either cocaine or amphetamines while in prison. Heroin was most likely to be used by those who had been using heroin during the immediate pre-imprisonment period, and particularly by the two-thirds of heroin users who considered themselves dependent. In view of the high prevalence of prior use of these drugs by individuals currently imprisoned, continuing attention is required to

  5. Sexual behavior induction of c-Fos in the nucleus accumbens and amphetamine-stimulated locomotor activity are sensitized by previous sexual experience in female Syrian hamsters.

    Science.gov (United States)

    Bradley, K C; Meisel, R L

    2001-03-15

    Dopamine transmission in the nucleus accumbens can be activated by drugs, stress, or motivated behaviors, and repeated exposure to these stimuli can sensitize this dopamine response. The objectives of this study were to determine whether female sexual behavior activates nucleus accumbens neurons and whether past sexual experience cross-sensitizes neuronal responses in the nucleus accumbens to amphetamine. Using immunocytochemical labeling, c-Fos expression in different subregions (shell vs core at the rostral, middle, and caudal levels) of the nucleus accumbens was examined in female hamsters that had varying amounts of sexual experience. Female hamsters, given either 6 weeks of sexual experience or remaining sexually naive, were tested for sexual behavior by exposure to adult male hamsters. Previous sexual experience increased c-Fos labeling in the rostral and caudal levels but not in the middle levels of the nucleus accumbens. Testing for sexual behavior increased labeling in the core, but not the shell, of the nucleus accumbens. To validate that female sexual behavior can sensitize neurons in the mesolimbic dopamine pathway, the locomotor responses of sexually experienced and sexually naive females to an amphetamine injection were then compared. Amphetamine increased general locomotor activity in all females. However, sexually experienced animals responded sooner to amphetamine than did sexually naive animals. These data indicate that female sexual behavior can activate neurons in the nucleus accumbens and that sexual experience can cross-sensitize neuronal responses to amphetamine. In addition, these results provide additional evidence for functional differences between the shell and core of the nucleus accumbens and across its anteroposterior axis.

  6. Impulsiveness, overactivity, and poorer sustained attention improve by chronic treatment with low doses of l-amphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD).

    Science.gov (United States)

    Sagvolden, Terje

    2011-03-30

    ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. The primary objective of the present research was to investigate behavioral effects of a range of doses of chronic l-amphetamine on ADHD-like symptoms in the SHR. The present study tested the behavioral effects of 0.75 and 2.2 mg l-amphetamine base/kg i.p. in male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. The striking impulsiveness, overactivity, and poorer sustained attention seen during baseline conditions in the SHR were improved by chronic treatment with l-amphetamine. The dose-response curves were, however, different for the different behaviors. Most significantly, the 0.75 mg/kg dose of l-amphetamine improved sustained attention without reducing overactivity and impulsiveness. The 2.2 mg/kg dose improved sustained attention as well as reduced SHR overactivity and impulsiveness. The effects of l-amphetamine to reduce the behavioral symptoms of ADHD in the SHR were maintained over the 14 days of daily dosing with no evidence of tolerance developing.

  7. Risk-assessment and risk-taking behavior predict potassium- and amphetamine-induced dopamine response in the dorsal striatum of rats

    Directory of Open Access Journals (Sweden)

    Sara ePalm

    2014-07-01

    Full Text Available Certain personality types and behavioral traits display high correlations to drug use and an increased level of dopamine in the reward system is a common denominator of all drugs of abuse. Dopamine response to drugs has been suggested to correlate with some of these personality types and to be a key factor influencing the predisposition to addiction. This study investigated if behavioral traits can be related to potassium- and amphetamine-induced dopamine response in the dorsal striatum, an area hypothesized to be involved in the shift from drug use to addiction. The open field and multivariate concentric square field™ tests were used to assess individual behavior in male Wistar rats. Chronoamperometric recordings were then made to study the potassium- and amphetamine-induced dopamine response in vivo. A classification based on risk-taking behavior in the open field was used for further comparisons. Risk-taking behavior was correlated between the behavioral tests and high risk takers displayed a more pronounced response to the dopamine uptake blocking effects of amphetamine. Behavioral parameters from both tests could also predict potassium- and amphetamine-induced dopamine responses showing a correlation between neurochemistry and behavior in risk-assessment and risk-taking parameters. In conclusion, the high risk-taking rats showed a more pronounced reduction of dopamine uptake in the dorsal striatum after amphetamine indicating that this area may contribute to the sensitivity of these animals to psychostimulants and proneness to addiction. Further, inherent dopamine activity was related to risk-assessment behavior, which may be of importance for decision-making and inhibitory control, key components in addiction.

  8. Methamphetamine, d-amphetamine and p-chloroamphetamine induced neurotoxicity differentially effect impulsive responding on the stop-signal task in rats

    Science.gov (United States)

    Furlong, Teri M.; Leavitt, Lee S.; Keefe, Kristen A.; Son, Jong-Hyun

    2016-01-01

    Abused amphetamines, such as d-amphetamine (AMPH) and methamphetamine (METH), are highly addictive and destructive to health and productive lifestyles. The abuse of these drugs is associated with impulsive behavior, which is likely to contribute to addiction. The amphetamines also differentially damage dopamine (DA) and serotonin (5-HT) systems, which regulate impulsive behavior; therefore, exposure to these drugs may differentially alter impulsive behavior to effect the progression of addiction. We examined the impact of neurotoxicity induced by three amphetamines on impulsive action using a stop-signal task in rats. Animals were rewarded with a food pellet after lever pressing (i.e. a go trial), unless an auditory cue was presented and withholding lever press gained reward (i.e. a stop trial). Animals were trained on the task and then exposed to a neurotoxic regimen of either AMPH, p-chloroamphetamine (PCA), or METH. These regimens preferentially reduced DA transporter levels in striatum, 5-HT transporter levels in prefrontal cortex, or both, respectively. Assessment of performance on the stop-signal task beginning one week after the treatment revealed that AMPH produced a deficit in go-trial performance, whereas PCA did not alter performance on either trial type. In contrast, METH produced a deficit in stop-trial performance (i.e. impulsive action) but not go-trial performance. These findings suggest that the different neurotoxic consequences of substituted amphetamines are associated with different effects on inhibitory control over behavior. Thus, the course of addiction and maladaptive behavior resulting from exposure to these substances is likely to differ. PMID:26846719

  9. The Study of the Differences of Attention Bias, Executive Functioning, and Reaction Time of Amphetamine Consumers in Comparison of Non Consumers

    Directory of Open Access Journals (Sweden)

    Nezamaldin Ghasemi

    2012-11-01

    Full Text Available Aim: Addiction to opium can be resulted to different effects. Current research designed in order to comprise if neuro-psychological functions among Amphetamine consumers and normal people. Method: Research design was causal-comparative design which performed in consumers and normal people. Research population was all opium consumers of Bahar city. Addict group included of 33 Amphetamine consumers who were referred to Baharestan addiction withdrawal center by snowball sampling. The comparison group included 39 normal people that matched with addict group with consideration of age, sex, education. All samples were studied by technical management of center and by using of perceptual diagnostic tests. Wisconsin cards, reaction time tests (simple, diagnostic, and selective and attention bias (Stroop was used. Results: the results of the research indicated that Amphetamine consumers were significantly different with normal people in consideration of error number, but there wasn’t significant difference on error in Wisconsin test. In reaction time Amphetamine consumers had least reaction time and highest number of errors, in three states. In simple trial there weren’t significant difference, but two groups were significant different in selective and diagnostic trial on time and number of errors. Also, there wasn’t significant difference on attention bias with consideration of error, but there was significant difference with consideration of time. Conclusion: on the basis of results it can be claimed Amphetamine consumption can be affected on neuro-cognitive functions. Identifying and understanding of these factors can be useful in better understanding of problem, and can be led to different therapeutic treatment.

  10. Adolescent D-amphetamine treatment in a rodent model of ADHD: Pro-cognitive effects in adolescence without an impact on cocaine cue reactivity in adulthood.

    Science.gov (United States)

    Jordan, Chloe J; Taylor, Danielle M; Dwoskin, Linda P; Kantak, Kathleen M

    2016-01-15

    Attention-deficit/hyperactivity disorder (ADHD) is comorbid with cocaine abuse. Whereas initiating ADHD medication in childhood does not alter later cocaine abuse risk, initiating medication during adolescence may increase risk. Preclinical work in the Spontaneously Hypertensive Rat (SHR) model of ADHD found that adolescent methylphenidate increased cocaine self-administration in adulthood, suggesting a need to identify alternatively efficacious medications for teens with ADHD. We examined effects of adolescent d-amphetamine treatment on strategy set shifting performance during adolescence and on cocaine self-administration and reinstatement of cocaine-seeking behavior (cue reactivity) during adulthood in male SHR, Wistar-Kyoto (inbred control), and Wistar (outbred control) rats. During the set shift phase, adolescent SHR needed more trials and had a longer latency to reach criterion, made more regressive errors and trial omissions, and exhibited slower and more variable lever press reaction times. d-Amphetamine improved performance only in SHR by increasing choice accuracy and decreasing errors and latency to criterion. In adulthood, SHR self-administered more cocaine, made more cocaine-seeking responses, and took longer to extinguish lever responding than control strains. Adolescent d-amphetamine did not alter cocaine self-administration in adult rats of any strain, but reduced cocaine seeking during the first of seven reinstatement test sessions in adult SHR. These findings highlight utility of SHR in modeling cognitive dysfunction and comorbid cocaine abuse in ADHD. Unlike methylphenidate, d-amphetamine improved several aspects of flexible learning in adolescent SHR and did not increase cocaine intake or cue reactivity in adult SHR. Thus, adolescent d-amphetamine was superior to methylphenidate in this ADHD model. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. D-amphetamine improves cognitive deficits and physical therapy promotes fine motor rehabilitation in a rat embolic stroke model

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Overgaard, K; Hildebrandt-Eriksen, E S

    2006-01-01

    regarding gross motor performance. CONCLUSIONS: After embolization, physical therapy improved fine motor performance and D-amph accelerated rehabilitation of cognitive performance as observed in the rats of the THERAPY and D-AMPH groups. As a result of the administration of a high dose of D-amph, the rats......BACKGROUND AND PURPOSE: The purpose of this study was to examine the effects of D-amphetamine (D-amph) and physical therapy separately or combined on fine motor performance, gross motor performance and cognition after middle cerebral artery thromboembolization in rats. METHODS: Seventy-four rats...... on days 21-28 after surgery, rats of the SHAM and THERAPY groups had better fine motor performance than those of the CONTROL (P cognitive performance than CONTROL rats (P

  12. Determination of amphetamine-type stimulants in oral fluid by solid-phase microextraction and gas chromatography-mass spectrometry

    International Nuclear Information System (INIS)

    Souza, Daniele Z.; Boehl, Paula O.; Comiran, Eloisa; Mariotti, Kristiane C.; Pechansky, Flavio; Duarte, Paulina C.A.V.; De Boni, Raquel; Froehlich, Pedro E.; Limberger, Renata P.

    2011-01-01

    Graphical abstract: Highlights: → Propylchloroformate derivatization of amphetamine-type stimulants in oral fluid. → Direct immersion solid-phase microextraction/gas chromatography-mass spectrometry. → Linear range 2(4)-256 ng mL -1 , detection limits 0.5-2 ng mL -1 . → Accuracy 98-112%, precision TM device has been developed and validated. Thereunto, in-matrix propylchloroformate derivatization followed by direct immersion solid-phase microextraction and gas chromatography-mass spectrometry were employed. Deuterium labeled AMP was used as internal standard for all the stimulants and analysis was performed using the selected ion monitoring mode. The detector response was linear for the studied drugs in the concentration range of 2-256 ng mL -1 (neat oral fluid), except for FEN, whereas the linear range was 4-256 ng mL -1 . The detection limits were 0.5 ng mL -1 (MET), 1 ng mL -1 (MPH) and 2 ng mL -1 (DIE, AMP, FEN), respectively. Accuracy of quality control samples remained within 98.2-111.9% of the target concentrations, while precision has not exceeded 15% of the relative standard deviation. Recoveries with Quantisal TM device ranged from 77.2% to 112.1%. Also, the goodness-of-fit concerning the ordinary least squares model in the statistical inference of data has been tested through residual plotting and ANOVA. The validated method can be easily automated and then used for screening and confirmation of amphetamine-type stimulants in drivers' oral fluid.

  13. The influence of R and S configurations of a series of amphetamine derivatives on quantitative structure–activity relationship models

    International Nuclear Information System (INIS)

    Fresqui, Maíra A.C.; Ferreira, Márcia M.C.; Trsic, Milan

    2013-01-01

    Highlights: ► The QSAR model is not dependent of ligand conformation. ► Amphetamines were analyzed by quantum chemical, steric and hydrophobic descriptors. ► CHELPG atomic charges on the benzene ring are one of the most important descriptors. ► The PLS models built were extensively validated. ► Manual docking supports the QSAR results by pi–pi stacking interactions. - Abstract: Chiral molecules need special attention in drug design. In this sense, the R and S configurations of a series of thirty-four amphetamines were evaluated by quantitative structure–activity relationship (QSAR). This class of compounds has antidepressant, anti-Parkinson and anti-Alzheimer effects against the enzyme monoamine oxidase A (MAO A). A set of thirty-eight descriptors, including electronic, steric and hydrophobic ones, were calculated. Variable selection was performed through the correlation coefficients followed by the ordered predictor selection (OPS) algorithm. Six descriptors (CHELPG atomic charges C3, C4 and C5, electrophilicity, molecular surface area and log P) were selected for both configurations and a satisfactory model was obtained by PLS regression with three latent variables with R 2 = 0.73 and Q 2 = 0.60, with external predictability Q 2 = 0.68, and R 2 = 0.76 and Q 2 = 0.67 with external predictability Q 2 = 0.50, for R and S configurations, respectively. To confirm the robustness of each model, leave-N-out cross validation (LNO) was carried out and the y-randomization test was used to check if these models present chance correlation. Moreover, both automated or a manual molecular docking indicate that the reaction of ligands with the enzyme occurs via pi–pi stacking interaction with Tyr407, inclined face-to-face interaction with Tyr444, while aromatic hydrogen–hydrogen interactions with Tyr197 are preferable for R instead of S configurations.

  14. Risk of amphetamine use disorder and mortality among incident users of prescribed stimulant medications in the Veterans Administration.

    Science.gov (United States)

    Westover, Arthur N; Nakonezny, Paul A; Halm, Ethan A; Adinoff, Bryon

    2018-05-01

    Non-medical use of prescribed stimulant medications is a growing concern. This study's aims were to ascertain the demographics of stimulant medication users compared with non-users, examine temporal trends of stimulant medication use and estimate risk factors for development of amphetamine use disorder (AUD) and mortality among new users of stimulant medications. Cox proportional hazards regression in a retrospective cohort adjusted by baseline covariates. United States, national administrative database of the Veterans Affairs (VA) health-care system. Adult incident users of stimulant medications (n = 78 829) from fiscal years (FY) 2001 to 2012. Primary outcomes were time-to-event: (1) occurrence of AUD diagnosis and (2) death. Baseline covariates included demographic information, Food and Drug Administration (FDA)-approved indications for stimulant use, substance use disorders (SUD) and depression. Stimulant users compared with non-users were younger, more likely to be non-Hispanic white and female. Incident stimulant medication users increased threefold from FY2001-FY2012 and eightfold among adults aged 18-44 years. Nearly one in 10 incident users in FY2012 had a comorbid baseline SUD. Off-label use was common-nearly three of every five incident users in FY2012. Comorbid SUDs among incident stimulant medication users were risk factors for occurrence of AUD during follow-up, with adjusted hazard ratio (AHR) estimates ranging from 1.54 to 2.83 (Ps users in the Veterans Affairs health-care system, measured from fiscal years 2001 to 2012, comorbid substance use disorders were common and were risk factors for development of an amphetamine use disorder (AUD). Increased mortality risk among incident users of stimulant medications was observed among both those who developed an AUD later and those whose use was defined as off-label. © 2017 Society for the Study of Addiction.

  15. On-line liquid chromatography/tandem mass spectrometry simultaneous determination of opiates, cocainics and amphetamines in dried blood spots.

    Science.gov (United States)

    Saussereau, E; Lacroix, C; Gaulier, J M; Goulle, J P

    2012-02-15

    A novel approach has been developed for the illicit drugs quantitative determination using dried blood spots (DBS) on filter paper. The illicit drugs tested were opiates (morphine and its 3- and 6-glucuronide metabolites, codeine, 6-monoacetylmorphine), cocainics (ecgonine methylester, benzoylecgonine, cocaine, cocaethylene) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA). The described method, requiring a small blood volume, is based on high performance liquid chromatography coupled to tandem mass spectrometry using on-line extraction. A Whatman card 903 was spotted with 30μL of whole blood and left overnight to dry at room temperature. A 3-mm diameter disk was removed using a manual punch, suspended in 150μL of water for 10min with ultrasonication, and then 100μL was injected in the on-line LC-MS/MS system. An Oasis HLB was used as an extraction column and a C18 Atlantis as an analytical column. The chromatographic cycle was performed with 20mM ammonium formate buffer (pH 2.8) (solvent A) and acetonitrile/solvent A (90:10, v/v) gradient in 16min. Detection was performed in positive electrospray ionization mode (ESI+) with a Quattro Micro (Waters). Recoveries of all analytes were up to 80%. DBS were stored in duplicate at 4°C and -20°C for up to 6 months. Illicit drugs seemed to be much more stabled at -20°C. Furthermore, it was tested whether analysis of DBS may be as reliable as that of whole blood investigating authentic samples; significant correlations were obtained. This DBS assay has potential as rapid, sensitive and inexpensive option for the illicit drugs determination in small blood volumes, which seems of great interest in suspected cases of driving under the influence of drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Chiral analysis of amphetamines in hair by liquid chromatography-tandem mass spectrometry: compliance-monitoring of attention deficit hyperactivity disorder (ADHD) patients under Elvanse® therapy and identification after controlled low-dose application.

    Science.gov (United States)

    Binz, Tina M; Williner, Elena; Strajhar, Petra; Dolder, Patrick C; Liechti, Matthias E; Baumgartner, Markus R; Kraemer, Thomas; Steuer, Andrea E

    2018-02-01

    Amphetamine (AMP) is used as an illicit drug and also for the treatment of attention deficit hyperactivity disorder (ADHD). Respective drugs most often contain the enantiomer (S)-AMP as active compound or (S)-AMP is formed from the prodrug lisdexamfetamine (Elvanse®) whereas the illicit drug is usually traded as racemate ((R/S)-AMP). A differentiation between the use of the medically prescribed drug and the abuse of illicit street amphetamine is of great importance, for example in retrospective consumption monitoring by hair analysis. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the chiral separation and quantitation of (S)- and (R)-AMP in hair was developed. For this purpose, 20 mg hair was extracted and derivatized with N-(2,4-dinitro-5-fluorophenyl)-L(S)-valinamide L(S)-(DNPV) to yield amphetamine diastereomers. Baseline separation of the resulting diastereomers was achieved on a high-pressure liquid-chromatography system (HPLC) coupled to a Sciex QTRAP® 5500 linear ion trap quadrupole mass spectrometer. The method was successfully validated. Analysis of hair samples from nine Elvanse® patients revealed only (S)-AMP in eight cases; one subject showed both enantiomers indicating a (side-) consumption of street amphetamine. The analysis of the 16 amphetamine users' samples showed only racemic amphetamine. Furthermore, it could be shown in a controlled study that (S)-AMP can be detected after administration of even very low doses of lisdexamfetamine and dexamphetamine, which can be of interest in forensic toxicology and especially in drug-facilitated crime (DFC). The method now enables the retrospective compliance-monitoring of ADHD patients and the differentiation between medically prescribed intake of (S)-amphetamine and abuse of illicit street amphetamine. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Development of a targeted GC/MS screening method and validation of an HPLC/DAD quantification method for piperazines–amphetamines mixtures in seized material

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    Yacine Boumrah

    2014-09-01

    Full Text Available Piperazine-related drugs are sold as party pills in the form of tablets, capsules, liquids or powders. These party pills can contain several piperazine derivatives, or even a mixture of piperazines and amphetamine derivatives. This paper describes a screening method using a gas chromatography–mass spectrometry technique allowing the separation and the identification of active components within these mixtures by a combined silylation and acylation derivatization procedure. The studied substances–namely: 1-benzylpiperazine (BZP, 1-(3,4-methylenedioxyben-zylpiperazine (MDBP, 1-(3-trifluoromethylphenylpiperazine (TFMPP, 1-(3-chlorophenyl piperazine (mCPP, 1-(4-methoxyphenyl piperazine (MeOPP, amphetamine, methamphetamine, ephedrine, pseudoephedrine, 3,4-methylenedioxy-N-methamphetamine (MDMA, 3,4-methylenedi-oxyamphetamine (MDA, 3,4-methylenedioxy-N-ethylamphetamine (MDEA and N-methyl-1,3-benzodioxolylbutanamine (MBDB–are separated.

  18. Development and validation of a magnetic solid-phase extraction with high-performance liquid chromatography method for the simultaneous determination of amphetamine and methadone in urine.

    Science.gov (United States)

    Taghvimi, Arezou; Hamishehkar, Hamed; Ebrahimi, Mahmoud

    2016-06-01

    The simultaneous determination of amphetamine and methadone was carried out by magnetic graphene oxide nanoparticles, a magnetic solid-phase extraction adsorbent, as a new sample treatment technique. The main factors (the amounts of sample volume, amount of adsorbent, type and amount of extraction organic solvent, time of extraction and desorption, pH, the ionic strength of extraction medium, and agitation rate) influencing the extraction efficiency were investigated and optimized. Under the optimized conditions, good linearity was observed in the range of 100-1500 ng/mL for amphetamine and 100-1000 ng/mL for methadone. The method was evaluated for determination of AM and methadone in positive urine samples, satisfactory results were obtained, therefore magnetic solid-phase extraction can be applied as a novel method for the determination of drugs of abuse in forensic laboratories. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Effects of 7-day continuous D-amphetamine, methylphenidate, and cocaine treatment on choice between methamphetamine and food in male rhesus monkeys.

    Science.gov (United States)

    Schwienteck, Kathryn L; Banks, Matthew L

    2015-10-01

    Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice. In addition, 7-day cocaine treatment effects were also examined. Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1mg/kg/h), methylphenidate (0.032-0.32mg/kg/h), or cocaine (0.1-0.32mg/kg/h). During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. The present subchronic treatment results support the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Adolescent THC exposure does not sensitize conditioned place preferences to subthreshold d-amphetamine in male and female rats [version 1; referees: 2 approved

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    Robin J Keeley

    2018-03-01

    Full Text Available The acute effects of marijuana consumption on brain physiology and behaviour are well documented, but the long-term effects of its chronic use are less well known. Chronic marijuana use during adolescence is of increased interest, given that the majority of individuals first use marijuana during this developmental stage , and  adolescent marijuana use is thought to increase the susceptibility to abusing other drugs when exposed later in life. It is possible that marijuana use during critical periods in adolescence could lead to increased sensitivity to other drugs of abuse later on. To test this, we chronically administered ∆9-tetrahydrocannabinol (THC to male and female Long-Evans (LER and Wistar (WR rats directly after puberty onset. Rats matured to postnatal day 90 before being exposed to a conditioned place preference task (CPP. A subthreshold dose of d-amphetamine, found not to induce place preference in drug naïve rats, was used as the unconditioned stimulus. The effect of d-amphetamine on neural activity was inferred by quantifying cfos expression in the nucleus accumbens and dorsal hippocampus following CPP training. Chronic exposure to THC post-puberty had no potentiating effect on a subthreshold dose of d-amphetamine to induce CPP. No differences in cfos expression were observed. These results show that chronic exposure to THC during puberty did not increase sensitivity to d-amphetamine in adult LER and WR rats. This supports the concept that THC may not sensitize the response to all drugs of abuse.

  1. Comparison of concentrations of drugs between blood samples with and without fluoride additive-important findings for Δ9-tetrahydrocannabinol and amphetamine.

    Science.gov (United States)

    Wiedfeld, Christopher; Krueger, Julia; Skopp, Gisela; Musshoff, Frank

    2018-02-17

    Fluoride is a common stabilizing agent in forensic toxicology to avoid the frequent problem of degradation of drugs in blood samples especially described for cocaine. In cases only samples with addition of fluoride are available, it is a crucial question if also concentrations of common drugs other than cocaine (amphetamines, opiates and cannabinoids) are affected by fluoride. So far, there are only rare literature data available on discrepant results especially for Δ 9 -tetrahydrocannabinol (THC). In this study, comparative analysis of positive tested paired routine plasma/serum samples (n = 375), collected at the same time point (one device with and one without fluoride), was carried out with special focus on cannabinoids. Samples were measured with validated routine liquid chromatography-tandem mass spectrometry methods for THC, 11-hydroxy-THC (THC-OH), 11-nor-9-carboxy-THC (THC-COOH), cocaine, benzoylecgonine, ecgonine methyl ester, morphine, codeine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, and 3,4-methylenedioxyethylamphetamine, and results were statistically evaluated. Beside the expected stabilization effect on cocaine and the consequently reduced concentration of ecgonine methyl ester in fluoride samples, benzoylecgonine was elevated compared to respective samples without fluoride. Most importantly, new findings were significantly reduced mean concentrations of THC (- 17%), THC-OH (- 17%), and THC-COOH (- 22%) in fluoride samples. Mean amphetamine concentration was significantly higher in samples with the additive (+ 6%). For the other amphetamine type of drugs as well as for morphine and codeine, no significant differences could be seen. Whenever specified thresholds have been set, such as in most European countries, the use of different blood sample systems may result in a motorist being differently charged or prosecuted. The findings will support forensic toxicologists at the

  2. Comparison of changes in the extracellular concentration of noradrenaline in rat frontal cortex induced by sibutramine or d-amphetamine: modulation by α2-adrenoceptors

    Science.gov (United States)

    Wortley, K E; Hughes, Z A; Heal, D J; Stanford, S C

    1999-01-01

    The effects of sibutramine (0.25–10 mg kg−1, i.p.) on extracellular noradrenaline concentration in the frontal cortex of halothane-anaesthetized rats were compared with those of d-amphetamine (1–3 mg kg−1, i.p.) using in vivo microdialysis. The role of presynaptic α2-adrenoceptors in modulating the effects of these drugs on extracellular noradrenaline concentration were also investigated by pretreating rats with the selective α2-adrenoceptor antagonist, RX821002.Sibutramine induced a gradual and sustained increase in extracellular noradrenaline concentration. The dose-response relationship was described by a bell-shaped curve with a maximum effect at 0.5 mg kg−1. In contrast, d-amphetamine induced a rapid increase in extracellular noradrenaline concentration, the magnitude of which paralleled drug dose.Pretreatment with the α2-adrenoceptor antagonist, RX821002 (dose 3 mg kg−1, i.p.) increased by 5 fold the accumulation of extracellular noradrenaline caused by sibutramine (10 mg kg−1) and reduced the latency of sibutramine to reach its maximum effect from 144–56 min.RX821002-pretreatment increased by only 2.5 fold the increase in extracellular noradrenaline concentration caused by d-amphetamine alone (10 mg kg−1) and had no effect on the latency to reach maximum.These findings support evidence that sibutramine acts as a noradrenaline uptake inhibitor in vivo and that the effects of this drug are blunted by indirect activation of presynaptic α2-adreno-ceptors. In contrast, the rapid increase in extracellular noradrenaline concentration induced by d-amphetamine is consistent with this being mainly due to an increase in Ca2+-independent release of noradrenaline. PMID:10482917

  3. Studies on the metabolism and toxicological detection of the amphetamine-like anorectic fenproporex in human urine by gas chromatography-mass spectrometry and fluorescence polarization immunoassay.

    Science.gov (United States)

    Kraemer, T; Theis, G A; Weber, A A; Maurer, H H

    2000-01-28

    Studies on the metabolism and the toxicological analysis of fenproporex (R,S-3-[(1-phenyl-2-propyl)-amino]-propionitrile, FP) using GC-MS and fluorescence polarization immunoassay are described. The metabolites were identified in urine samples of volunteers by GC-MS after cleavage of conjugates, extraction and acetylation. Besides unchanged FP, fourteen metabolites, including amphetamine, could be identified. Two partially overlapping metabolic pathways could be postulated: ring degradation by one- and two-fold aromatic hydroxylation followed by methylation and side chain degradation by N-dealkylation to amphetamine (AM). A minor pathway leads via beta-hydroxylation of AM to norephedrine. For GC-MS detection, the systematic toxicological analysis procedure including acid hydrolysis, extraction at pH 8-9 and acetylation was suitable (detection limits 50 ng/ml for FP and 100 ng/ml for AM). Excretion studies showed, that only AM but neither FP nor its specific metabolites were detectable 30-60 h after ingestion of 20 mg of FP. Therefore, misinterpretation can occur. The Abbott TDx FPIA amphetamine/methamphetamine II gave positive results up to 58 h. All the positive immunoassay results could be confirmed by the described GC-MS procedure.

  4. Neuropharmacology of new psychoactive substances (NPS: focus on the rewarding and reinforcing properties of cannabimimetics and amphetamine-like stimulants

    Directory of Open Access Journals (Sweden)

    Cristina eMiliano

    2016-04-01

    Full Text Available New psychoactive substances (NPS are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, dark net as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society (UNODC, World Drug Report, 2014; EMCDDA, European Drug Report 2014: Trends and developments. The chemical structure (phenethylamines, piperazine, cathinones, tryptamines, synthetic cannabinoids of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%(WDR, 2014. Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: cannabimimetics (JWH, HU, CP series and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone and MDMA analogues. Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ9-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of

  5. The influence of R and S configurations of a series of amphetamine derivatives on quantitative structure-activity relationship models

    Energy Technology Data Exchange (ETDEWEB)

    Fresqui, Maira A.C., E-mail: maira@iqsc.usp.br [Institute of Chemistry of Sao Carlos, University of Sao Paulo, Av. Trabalhador Sao-carlense, 400, POB 780, 13560-970 Sao Carlos, SP (Brazil); Ferreira, Marcia M.C., E-mail: marcia@iqm.unicamp.br [Institute of Chemistry, University of Campinas - UNICAMP, POB 6154, 13083-970 Campinas, SP (Brazil); Trsic, Milan, E-mail: cra612@gmail.com [Institute of Chemistry of Sao Carlos, University of Sao Paulo, Av. Trabalhador Sao-carlense, 400, POB 780, 13560-970 Sao Carlos, SP (Brazil)

    2013-01-08

    Highlights: Black-Right-Pointing-Pointer The QSAR model is not dependent of ligand conformation. Black-Right-Pointing-Pointer Amphetamines were analyzed by quantum chemical, steric and hydrophobic descriptors. Black-Right-Pointing-Pointer CHELPG atomic charges on the benzene ring are one of the most important descriptors. Black-Right-Pointing-Pointer The PLS models built were extensively validated. Black-Right-Pointing-Pointer Manual docking supports the QSAR results by pi-pi stacking interactions. - Abstract: Chiral molecules need special attention in drug design. In this sense, the R and S configurations of a series of thirty-four amphetamines were evaluated by quantitative structure-activity relationship (QSAR). This class of compounds has antidepressant, anti-Parkinson and anti-Alzheimer effects against the enzyme monoamine oxidase A (MAO A). A set of thirty-eight descriptors, including electronic, steric and hydrophobic ones, were calculated. Variable selection was performed through the correlation coefficients followed by the ordered predictor selection (OPS) algorithm. Six descriptors (CHELPG atomic charges C3, C4 and C5, electrophilicity, molecular surface area and log P) were selected for both configurations and a satisfactory model was obtained by PLS regression with three latent variables with R{sup 2} = 0.73 and Q{sup 2} = 0.60, with external predictability Q{sup 2} = 0.68, and R{sup 2} = 0.76 and Q{sup 2} = 0.67 with external predictability Q{sup 2} = 0.50, for R and S configurations, respectively. To confirm the robustness of each model, leave-N-out cross validation (LNO) was carried out and the y-randomization test was used to check if these models present chance correlation. Moreover, both automated or a manual molecular docking indicate that the reaction of ligands with the enzyme occurs via pi-pi stacking interaction with Tyr407, inclined face-to-face interaction with Tyr444, while aromatic hydrogen-hydrogen interactions with Tyr197 are preferable

  6. Ventral Tegmental Area Dopamine Cell Activation during Male Rat Sexual Behavior Regulates Neuroplasticity and d-Amphetamine Cross-Sensitization following Sex Abstinence.

    Science.gov (United States)

    Beloate, Lauren N; Omrani, Azar; Adan, Roger A; Webb, Ian C; Coolen, Lique M

    2016-09-21

    Experience with sexual behavior causes cross-sensitization of amphetamine reward, an effect dependent on a period of sexual reward abstinence. We previously showed that ΔFosB in the nucleus accumbens (NAc) is a key mediator of this cross-sensitization, potentially via dopamine receptor activation. However, the role of mesolimbic dopamine for sexual behavior or cross-sensitization between natural and drug reward is unknown. This was tested using inhibitory designer receptors exclusively activated by designer drugs in ventral tegmental area (VTA) dopamine cells. rAAV5/hSvn-DIO-hm4D-mCherry was injected into the VTA of TH::Cre adult male rats. Males received clozapine N-oxide (CNO) or vehicle injections before each of 5 consecutive days of mating or handling. Following an abstinence period of 7 d, males were tested for amphetamine conditioned place preference (CPP). Next, males were injected with CNO or vehicle before mating or handling for analysis of mating-induced cFos, sex experience-induced ΔFosB, and reduction of VTA dopamine soma size. Results showed that CNO did not affect mating behavior. Instead, CNO prevented sexual experience-induced cross-sensitization of amphetamine CPP, ΔFosB in the NAc and medial prefrontal cortex, and decreases in VTA dopamine soma size. Expression of hm4D-mCherry was specific to VTA dopamine cells and CNO blocked excitation and mating-induced cFos expression in VTA dopamine cells. These findings provide direct evidence that VTA dopamine activation is not required for initiation or performance of sexual behavior. Instead, VTA dopamine directly contributes to increased vulnerability for drug use following loss of natural reward by causing neuroplasticity in the mesolimbic pathway during the natural reward experience. Drugs of abuse act on the neural pathways that mediate natural reward learning and memory. Exposure to natural reward behaviors can alter subsequent drug-related reward. Specifically, experience with sexual behavior

  7. Identificação de anfetamina em amostras de cabelo por imunofluorescência polarizada Amphetamine detection in hair samples by FPIA

    Directory of Open Access Journals (Sweden)

    Saulo Rios Mariz

    2003-03-01

    Full Text Available O uso indevido de anfetaminas tem preocupado as autoridades sanitárias em todo o mundo. No Brasil, destacam-se os anorexígenos anfetamínicos como o femproporex, que, no organismo, se biotransforma em anfetamina. Apesar de ser controlado por legislação específica, este fármaco tem sido amplamente utilizado em nosso país. Nas análises toxicológicas para verificação do uso de fármacos e drogas de abuso, têm-se empregado diferentes amostras biológicas. Mais recentemente a utilização do cabelo tem sido preconizada principalmente por informar sobre um uso a longo prazo da substância. A técnica para identificação de anfetaminas em cabelo é a cromatografia em fase gasosa acoplada à espectrometria de massas (CG-EM. A partir de um método descrito na literatura foram desenvolvidos estudos para avaliação da imunofluorescência polarizada como técnica de triagem na identificaçao de anfetamina em cabelo de usuários de anfetamínicos. Os resultados obtidos indicam que o método otimizado pode ser utilizado como triagem na identificação de anfetamina em cabelo.The amphetamine abuse is a preoccupation of public health authorities all over the world. In Brazil, anoretic drugs like fenproporex have been much used. Fenproporex is metabolically dealkylated to amphetamine in the human body. In spite of its legal control, it has been abused in the country. Different samples have been used to identify the drug in toxicological analyses. Hair samples have been proposed recently to identify and study the long-term use of the drug. CG-MG is the technique used to identify amphetamines in hair samples. Following a method proposed in specific literature, some studies have been developed to evaluate the application of the fluorescence polarization imunoassay (FPIA to identify amphetamine in hair samples of fenproporex users. The results show that the standard method may be used as screening in the identification of amphetamine by FPIA in hair

  8. Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats

    International Nuclear Information System (INIS)

    Milesi-Halle, Alessandra; Hendrickson, Howard P.; Laurenzana, Elizabeth M.; Gentry, W. Brooks; Owens, S. Michael

    2005-01-01

    These studies investigated how (+)-methamphetamine (METH) dose and rat sex affect the pharmacological response to METH in Sprague-Dawley rats. The first set of experiments determined the pharmacokinetics of METH and its pharmacologically active metabolite (+)-amphetamine (AMP) in male and female Sprague-Dawley rats after 1.0 and 3.0 mg/kg METH doses. The results showed significant sex-dependent changes in METH pharmacokinetics, and females formed significantly lower amounts of AMP. While the area under the serum concentration-time curve in males increased proportionately with the METH dose, the females showed a disproportional increase. The sex differences in systemic clearance, renal clearance, volume of distribution, and percentage of unchanged METH eliminated in the urine suggested dose-dependent pharmacokinetics in female rats. The second set of studies sought to determine the behavioral implications of these pharmacokinetic differences by quantifying locomotor activity in male and female rats after saline, 1.0, and 3.0 mg/kg METH. The results showed sex- and dose-dependent differences in METH-induced locomotion, including profound differences in the temporal profile of effects at higher dose. These findings show that the pharmacokinetic and metabolic profile of METH (slower METH clearance and lower AMP metabolite formation) plays a significant role in the differential pharmacological response to METH in male and female rats

  9. Cocaine-and Amphetamine Regulated Transcript (CART) Peptide Is Expressed in Precursor Cells and Somatotropes of the Mouse Pituitary Gland

    Science.gov (United States)

    Mortensen, Amanda H.

    2016-01-01

    Cocaine-and Amphetamine Regulated Transcript (CART) peptide is expressed in the brain, endocrine and neuroendocrine systems and secreted into the serum. It is thought to play a role in regulation of hypothalamic pituitary functions. Here we report a spatial and temporal analysis of Cart expression in the pituitaries of adult and developing normal and mutant mice with hypopituitarism. We found that Prop1 is not necessary for initiation of Cart expression in the fetal pituitary at e14.5, but it is required indirectly for maintenance of Cart expression in the postnatal anterior pituitary gland. Pou1f1 deficiency has no effect on Cart expression before or after birth. There is no 1:1 correspondence between CART and any particular cell type. In neonates, CART is detected primarily in non-proliferating, POU1F1-positive cells. CART is also found in some cells that express TSH and GH suggesting a correspondence with committed progenitors of the POU1F1 lineage. In summary, we have characterized the normal temporal and cell specific expression of CART in mouse development and demonstrate that postnatal CART expression in the pituitary gland requires PROP1. PMID:27685990

  10. Cocaine-and Amphetamine Regulated Transcript (CART Peptide Is Expressed in Precursor Cells and Somatotropes of the Mouse Pituitary Gland.

    Directory of Open Access Journals (Sweden)

    Amanda H Mortensen

    Full Text Available Cocaine-and Amphetamine Regulated Transcript (CART peptide is expressed in the brain, endocrine and neuroendocrine systems and secreted into the serum. It is thought to play a role in regulation of hypothalamic pituitary functions. Here we report a spatial and temporal analysis of Cart expression in the pituitaries of adult and developing normal and mutant mice with hypopituitarism. We found that Prop1 is not necessary for initiation of Cart expression in the fetal pituitary at e14.5, but it is required indirectly for maintenance of Cart expression in the postnatal anterior pituitary gland. Pou1f1 deficiency has no effect on Cart expression before or after birth. There is no 1:1 correspondence between CART and any particular cell type. In neonates, CART is detected primarily in non-proliferating, POU1F1-positive cells. CART is also found in some cells that express TSH and GH suggesting a correspondence with committed progenitors of the POU1F1 lineage. In summary, we have characterized the normal temporal and cell specific expression of CART in mouse development and demonstrate that postnatal CART expression in the pituitary gland requires PROP1.

  11. Fragmentation Pathways of Trifluoroacetyl Derivatives of Methamphetamine, Amphetamine, and Methylenedioxyphenylalkylamine Designer Drugs by Gas Chromatography/Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Takeshi Kumazawa

    2011-01-01

    Full Text Available Methamphetamine (MA, amphetamine (AM, and the methylenedioxyphenylalkylamine designer drugs, such as 3,4-methylenedioxymethamphetamine (MDMA, 3,4-methylenedioxyethylamphetamine (MDEA, N-methyl-1-(3,4-methylenedioxyphenyl-2-butanamine (MBDB, 3,4-methylenedioxyamphetamine (MDA, and 3,4-(methylenedioxyphenyl-2-butanamine (BDB, are widely abused as psychedelics. In this paper, these compounds were derivatized with trifluoroacetic (TFA anhydride and analyzed by gas chromatography/mass spectrometry using electron ionization in positive mode. Gas chromatographic separation for TFA derivatives of all compounds was successfully resolved using an Equity-5 fused silica capillary column with a poly (5% diphenyl-95% dimethylsiloxane stationary phase. Base peaks or prominent peaks of MA, AM, MDMA, MDEA, MBDB, MDA, and BDB appeared at m/z 154, 140, 154, 168, 168, 135, and 135, respectively. These occurred due to α-cleavage from the amide nitrogen, splitting into the TFA imine species and benzyl or methylenedioxybenzyl cations. Further prominent fragment ions at m/z 118 for MA and AM, m/z 162 for MDMA, MDEA, and MDA, and m/z 176 for MBDB and BDB were produced by cleavage of the phenylpropane or methylenedioxypropane hydrocarbon radical cation via a hydrogen rearrangement. These fragmentation pathways for the TFA derivatives of all the compounds are summarized and illustrated in this paper.

  12. The effects of clinically relevant doses of amphetamine and methylphenidate on signal detection and DRL in rats

    Science.gov (United States)

    Andrzejewski, Matthew E.; Spencer, Robert C.; Harris, Rachel L.; Feit, Elizabeth C.; McKee, Brenda L.; Berridge, Craig W.

    2014-01-01

    Low dose amphetamine (AMPH) and methylphenidate (MPH, Ritalin®) are the most widely prescribed and most effective pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD). Certain low, clinically relevant doses of MPH improve sustained attention and working memory in normal rats, in contrast to higher doses that impair cognitive ability and induce locomotor activity. However, the effects of AMPH of MPH on sustained attention and behavioral inhibition remain poorly characterized. The present experiments examined the actions of AMPH (0.1 and 0.25 mg/kg) and MPH (0.5 and 1.0 mg/kg) in a rat model of 1) sustained attention, where signal and blank trials were interspersed randomly and occurred at unpredictable times, and 2) behavioral inhibition, using a differential reinforcement of low rate (DRL) schedule. In a signal detection paradigm, both 0.5 mg/kg and 1.0 mg/kg MPH and 0.25 mg/kg AMPH improve sustained attention, however neither AMPH nor MPH improve behavioral inhibition on DRL. Taken together with other recent studies, it appears that clinically-relevant doses of AMPH and MPH may preferentially improve attention-related behavior while having little effect on behavioral inhibition. These observations provide additional insight into the basic behavioral actions of low-dose psychostimulants and further suggest that the use of sustained attention tasks may be important in the development of novel pharmacological treatments for ADHD. PMID:24467844

  13. Role of calcium in phosphoinositide metabolism and inhibition of norepinephrine transport into synaptic vesicles by amphetamine analogs

    International Nuclear Information System (INIS)

    Knepper, S.M.

    1985-01-01

    Norepinephrine-(NE) and calcium ionophore A23187-stimulated phosphoinositide (PIn) metabolism in rat brain slices was studied under varying calcium conditions. Tissue was labelled with 3 H-myo-inositol and 3 H-inositol phosphates (IPn), products of PIn metabolism were measured. In the absence of media calcium the response to NE was decreased while that to A23187 was little affected A23187 can release calcium from intracellular stores. Basal and stimulated accumulation of 3 H-IPn was reversibly antagonized with EGTA by addition of calcium. Using calcium buffers, approximately 10 -7 M free calcium was required to support hydrolysis. Free intracellular calcium is maintained at approximately this level. Thus calcium is required for PIn hydrolysis but appears to play a permissive role, basal levels being sufficient to support metabolism. Conformationally-defined (rigid) and -restricted (semi-rigid) analogs of the most stable conformations of amphetamine, antiperiplanar (exo) and gauche (endo), were utilized to probe the conformational requirements of vesicular NE transport. Analogs tested were 2-aminotetralin (2AT), 3-methyltetrahydroisoquinoline, anti- and syn-9-aminobenzobicyclo[2.2.1]heptene, and endo and exo conformers of 2-aminobenzobicyclo[2.2.1]heptene and 2-aminobenzobicyclo[2.2.2]octene

  14. Fragmentation Pathways of Trifluoroacetyl Derivatives of Methamphetamine, Amphetamine, and Methylenedioxyphenyl alkylamine Designer Drugs by Gas Chromatography/Mass Spectrometry

    International Nuclear Information System (INIS)

    Kumazawa, T.; Xiao-Pen, L.; Sato, K.

    2011-01-01

    Methamphetamine (MA), amphetamine (AM), and the methylenedioxyphenyl alkylamine designer drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy ethylamphetamine (MDEA), N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), 3,4-methylenedioxyamphetamine (MDA), and 3,4-(methylenedioxyphenyl)-2-butanamine (BDB), are widely abused as psychedelics. In this paper, these compounds were derivatized with trifluoroacetic (TFA) anhydride and analyzed by gas chromatography/mass spectrometry using electron ionization in positive mode. Gas chromatographic separation for TFA derivatives of all compounds was successfully resolved using an Equity-5 fused silica capillary column with a poly (5% diphenyl-95% dimethylsiloxane) stationary phase. Base peaks or prominent peaks of MA, AM, MDMA, MDEA, MBDB, MDA, and BDB appeared at m/z 154, 140, 154, 168, 168, 135, and 135, respectively. These occurred due to a-cleavage from the amide nitrogen, splitting into the TFA imine species and benzyl or methylenedioxybenzyl cations. Further prominent fragment ions at m/z 118 for MA and AM, m/z 162 for MDMA, MDEA, and MDA, and m/z 176 for MBDB and BDB were produced by cleavage of the phenylpropane or methylenedioxy propane hydrocarbon radical cation via a hydrogen rearrangement. These fragmentation pathways for the TFA derivatives of all the compounds are summarized and illustrated in this paper.

  15. Genetic Regulation of Hypothalamic Cocaine and Amphetamine-Regulated Transcript (CART) in BxD Inbred Mice

    Science.gov (United States)

    Hawks, Brian W.; Li, Wei; Garlow, Steven J.

    2009-01-01

    Cocaine-Amphetamine Regulated Transcript (CART) peptides are implicated in a wide range of behaviors including in the reinforcing properties of psychostimulants, feeding and energy balance and stress and anxiety responses. We conducted a complex trait analysis to examine natural variation in the regulation of CART transcript abundance (CARTta) in the hypothalamus. CART transcript abundance was measured in total hypothalamic RNA from 26 BxD recombinant inbred (RI) mouse strains and in the C57BL/6 (B6) and DBA/2J (D2) progenitor strains. The strain distribution pattern for CARTta was continuous across the RI panel, which is consistent with this being a quantitative trait. Marker regression and interval mapping revealed significant quantitative trait loci (QTL) on mouse chromosome 4 (around 58.2cM) and chromosome 11 (between 20–36cM) that influence CARTta and account for 31% of the between strain variance in this phenotype. There are numerous candidate genes and QTL in these chromosomal regions that may indicate shared genetic regulation between CART expression and other neurobiological processes referable to known actions of this neuropeptide. PMID:18199428

  16. The dopamine transporter gene may not contribute to susceptibility and the specific personality traits of amphetamine dependence.

    Science.gov (United States)

    Tzeng, Nian-Sheng; Lu, Ru-Band; Yeh, Hui-Wen; Yeh, Yi-Wei; Huang, Chang-Chih; Yen, Che-Hung; Kuo, Shin-Chang; Chen, Chun-Yen; Chang, Hsin-An; Ho, Pei-Shen; Cheng, Serena; Shih, Mei-Chen; Huang, San-Yuan

    2015-04-01

    A substantial amount of evidence suggests that dysfunction of the dopamine transporter may be involved in the pathophysiology of amphetamine dependence (AD). The aim of this study was to examine whether the dopamine transporter gene (DAT1, SLC6A3) is associated with development of AD and whether this gene influences personality traits in patients with AD. Eighteen polymorphisms of the DAT1 gene were analyzed in a case-control study that included 909 Han Chinese men (568 patients with AD and 341 control subjects). The patients fulfilled the DSM-IV-TR criteria for AD. The Tridimensional Personality Questionnaire (TPQ) was used to assess personality traits and to examine the association between these traits and DAT1 gene variants. A weak association was found between the rs27072 polymorphism and development of AD, but these borderline associations were unconfirmed by logistic regression and haplotype analysis. Although harm avoidance and novelty seeking scores were significantly higher in patients than in controls, DAT1 polymorphisms did not influence these scores. This study suggests that high harm avoidance and novelty seeking personality traits may be a risk factor for the development of AD. However, the DAT1 gene may not contribute to AD susceptibility and specific personality traits observed in AD among Han Chinese men. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Concurrent choice for social interaction and amphetamine using conditioned place preference in rats: effects of age and housing condition.

    Science.gov (United States)

    Yates, Justin R; Beckmann, Joshua S; Meyer, Andrew C; Bardo, Michael T

    2013-05-01

    Social interaction can serve as a natural reward that attenuates drug reward in rats; however, it is unknown if age or housing conditions alter the choice between social interaction and drug. Individually- and pair-housed adolescent and adult male rats were tested using conditioned place preference (CPP) in separate experiments in which: (1) social interaction was conditioned against no social interaction; (2) amphetamine (AMPH; 1mg/kg, s.c.) was conditioned against saline; or (3) social interaction was conditioned against AMPH. Social interaction CPP was obtained only in individually-housed adolescents, whereas AMPH CPP was obtained in both individually-housed adolescents and adults; however, the effect of AMPH was not statistically significant in pair-housed adults. When allowed to choose concurrently between compartments paired with either social interaction or AMPH, individually-housed adolescents preferred the compartment paired with social interaction, whereas pair-housed adolescents preferred the compartment paired with AMPH. Regardless of housing condition, adults showed a similar preference for the compartments paired with either social interaction or AMPH. Although some caution is needed in interpreting cross-experiment comparisons, the overall results suggest that individually-housed adolescents were most sensitive to the rewarding effect of social interaction, and this hypersensitivity to social reward effectively competed with AMPH reward. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Effects of environmental enrichment and paradoxical sleep deprivation on open-field behavior of amphetamine-treated mice.

    Science.gov (United States)

    Fukushiro, Daniela Fukue; Calzavara, Mariana Bendlin; Trombin, Thaís Fernanda; Lopez, Giorgia Batlle; Abílio, Vanessa Costhek; Andersen, Monica Levy; Tufik, Sergio; Frussa-Filho, Roberto

    2007-11-23

    Environmental enrichment or paradoxical sleep deprivation (PSD) has been shown to modify some responses elicited by drugs of abuse. The aims of the present study were to examine the effects of environmental enrichment and PSD, conducted separately or in association, on open-field behavior elicited by amphetamine (AMP) in mice. Male C57BL/6 mice were randomly assigned to live in either an enriched environmental condition (EC) or a standard environmental condition (SC) for 12 months since weaning. Some of the EC and SC mice were sleep deprived for 48 h, while others were maintained in their home-cages. Immediately after PSD or home-cage stay, the animals received an ip injection of saline, 2.5 mg/kg AMP or 5.0 mg/kg AMP. Fifteen minutes later, their open-field behavior was quantified. Whereas PSD enhanced total and peripheral locomotor activity of acutely AMP-treated mice, environmental enrichment presented only a trend toward enhancement. When PSD and environmental enrichment were combined, an increase in the total and peripheral locomotion frequencies of AMP-treated animals, similar to that observed after PSD, was revealed. In addition, PSD, environmental enrichment or their combination did not modify the effects of AMP on the other open-field behavioral parameters that were analyzed. The present findings demonstrate that some (but not all) of the behavioral effects caused by AMP acute administration can be similarly and specifically enhanced by both environmental enrichment and PSD in C57BL/6 mice.

  19. Amphetamine-type stimulant use and conditional paths of consumption: data from the Second Brazilian National Alcohol and Drugs Survey

    Directory of Open Access Journals (Sweden)

    Luciana T.S. Massaro

    2017-07-01

    Full Text Available Objective: The aim of this study was to estimate nationally representative prevalence rates of amphetamine-type stimulant (ATS use and to identify consumption-associated factors, proposing a conditional model of direct and indirect consumption paths. Method: Using data from the Second Brazilian National Alcohol and Drugs Survey, this cross-sectional study analyzed a subsample of 3,828 participants between 15 and 64 years old, gathering information on the use of psychoactive substances in a probabilistic sample of the Brazilian household population. Results: Rates of lifetime and last-year ATS use were, respectively, 4.1 and 1.6%. Economically privileged individuals and users of other substances were more at risk for using ATS. The results suggest that higher education decreases the chances of ATS consumption. The conditional model showed that higher income increased ATS use, higher education lowered the odds of such an increase, and cocaine use cancelled that associative effect. Conclusion: Brazil presents high rates of ATS use. Prevention and treatment strategies should focus on the protective effect of higher education levels and should target polydrug use. Knowledge of ATS-associated factors and user profiles is the starting point for developing effective treatments and tailored prevention strategies.

  20. One Hundred False-Positive Amphetamine Specimens Characterized by Liquid Chromatography Time-of-Flight Mass Spectrometry.

    Science.gov (United States)

    Marin, Stephanie J; Doyle, Kelly; Chang, Annie; Concheiro-Guisan, Marta; Huestis, Marilyn A; Johnson-Davis, Kamisha L

    2016-01-01

    Some amphetamine (AMP) and ecstacy (MDMA) urine immunoassay (IA) kits are prone to false-positive results due to poor specificity of the antibody. We employed two techniques, high-resolution mass spectrometry (HRMS) and an in silico structure search, to identify compounds likely to cause false-positive results. Hundred false-positive IA specimens for AMP and/or MDMA were analyzed by an Agilent 6230 time-of-flight (TOF) mass spectrometer. Separately, SciFinder (Chemical Abstracts) was used as an in silico structure search to generate a library of compounds that are known to cross-react with AMP/MDMA IAs. Chemical formulas and exact masses of 145 structures were then compared against masses identified by TOF. Compounds known to have cross-reactivity with the IAs were identified in the structure-based search. The chemical formulas and exact masses of 145 structures (of 20 chemical formulas) were compared against masses identified by TOF. Urine analysis by HRMS correlates accurate mass with chemical formulae, but provides little information regarding compound structure. Structural data of targeted antigens can be utilized to correlate HRMS-derived chemical formulas with structural analogs. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Purification and characterisation of a new hypothalamic satiety peptide, cocaine and amphetamine regulated transcript (CART), produced in yeast.

    Science.gov (United States)

    Thim, L; Nielsen, P F; Judge, M E; Andersen, A S; Diers, I; Egel-Mitani, M; Hastrup, S

    1998-05-29

    Cocaine and amphetamine regulated transcript (CART) is a newly discovered hypothalamic peptide with a potent appetite suppressing activity following intracerebroventricular administration. When the mature rat CART sequence encoding CART(1-102) was inserted in the yeast expression plasmid three CART peptides could be purified from the fermentation broth reflecting processing at dibasic sequences. None of these corresponded to the naturally occurring CART(55-102). In order to obtain CART(55-102) the precursor Glu-Glu-Ile-Asp-CART(55-102) has been produced and CART(55-102) was generated by digestion of the precursor with dipeptidylaminopeptidase-1. All four generated CART peptides have been characterised by N-terminal amino acid sequencing and mass spectrometry. The CART peptides contain six cysteine residues and using the yeast expressed CART(62-102) the disulphide bond configuration was found to be I-III, II-V and IV-VI. When the four CART peptides were intracerebroventricularly injected in fasted mice (0.1 to 2.0 microg) they all produced a dose dependent inhibition of food intake.

  2. Identification of specific markers for amphetamine synthesised from the pre-precursor APAAN following the Leuckart route and retrospective search for APAAN markers in profiling databases from Germany and the Netherlands.

    Science.gov (United States)

    Hauser, Frank M; Rößler, Thorsten; Hulshof, Janneke W; Weigel, Diana; Zimmermann, Ralf; Pütz, Michael

    2018-04-01

    α-Phenylacetoacetonitrile (APAAN) is one of the most important pre-precursors for amphetamine production in recent years. This assumption is based on seizure data but there is little analytical data available showing how much amphetamine really originated from APAAN. In this study, several syntheses of amphetamine following the Leuckart route were performed starting from different organic compounds including APAAN. The organic phases were analysed using gas chromatography-mass spectrometry (GC-MS) to search for signals caused by possible APAAN markers. Three compounds were discovered, isolated, and based on the performed syntheses it was found that they are highly specific for the use of APAAN. Using mass spectra, high resolution MS and nuclear magnetic resonance (NMR) data the compounds were characterised and identified as 2-phenyl-2-butenenitrile, 3-amino-2-phenyl-2-butenenitrile, and 4-amino-6-methyl-5-phenylpyrimidine. To investigate their significance, they were searched in data from seized amphetamine samples to determine to what extent they were present in illicitly produced amphetamine. Data of more than 580 cases from amphetamine profiling databases in Germany and the Netherlands were used for this purpose. These databases allowed analysis of the yearly occurrence of the markers going back to 2009. The markers revealed a trend that was in agreement with seizure reports and reflected an increasing use of APAAN from 2010 on. This paper presents experimental proof that APAAN is indeed the most important pre-precursor of amphetamine in recent years. It also illustrates how important it is to look for new ways to identify current trends in drug production since such trends can change within a few years. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Dissociation in effects of lesions of the nucleus accumbens core and shell on appetitive pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by D-amphetamine.

    Science.gov (United States)

    Parkinson, J A; Olmstead, M C; Burns, L H; Robbins, T W; Everitt, B J

    1999-03-15

    Dopamine release within the nucleus accumbens (NAcc) has been associated with both the rewarding and locomotor-stimulant effects of abused drugs. The functions of the NAcc core and shell were investigated in mediating amphetamine-potentiated conditioned reinforcement and locomotion. Rats were initially trained to associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After excitotoxic lesions that selectively destroyed either the NAcc core or shell, animals underwent additional CS-US training sessions and then were tested for the acquisition of a new instrumental response that produced the CS acting as a conditioned reinforcer (CR). Animals were infused intra-NAcc with D-amphetamine (0, 1, 3, 10, or 20 microg) before each session. Shell lesions affected neither Pavlovian nor instrumental conditioning but completely abolished the potentiative effect of intra-NAcc amphetamine on responding with CR. Core-lesioned animals were impaired during the Pavlovian retraining sessions but showed no deficit in the acquisition of responding with CR. However, the selectivity in stimulant-induced potentiation of the CR lever was reduced, as intra-NAcc amphetamine infusions dose-dependently increased responding on both the CR lever and a nonreinforced (control) lever. Shell lesions produced hypoactivity and attenuated amphetamine-induced activity. In contrast, core lesions resulted in hyperactivity and enhanced the locomotor-stimulating effect of amphetamine. These results indicate a functional dissociation of subregions of the NAcc; the shell is a critical site for stimulant effects underlying the enhancement of responding with CR and locomotion after intra-NAcc injections of amphetamine, whereas the core is implicated in mechanisms underlying the expression of CS-US associations.

  4. Cocaine- and amphetamine-regulated transcript (CART signaling within the paraventricular thalamus modulates cocaine-seeking behaviour.

    Directory of Open Access Journals (Sweden)

    Morgan H James

    Full Text Available BACKGROUND: Cocaine- and amphetamine-regulated transcript (CART has been demonstrated to play a role in regulating the rewarding and reinforcing effects of various drugs of abuse. A recent study demonstrated that i.c.v. administration of CART negatively modulates reinstatement of alcohol seeking, however, the site(s of action remains unclear. We investigated the paraventricular thalamus (PVT as a potential site of relapse-relevant CART signaling, as this region is known to receive dense innervation from CART-containing hypothalamic cells and to project to a number of regions known to be involved in mediating reinstatement, including the nucleus accumbens (NAC, medial prefrontal cortex (mPFC and basolateral amygdala (BLA. METHODOLOGY/PRINCIPAL FINDINGS: Male rats were trained to self-administer cocaine before being extinguished to a set criterion. One day following extinction, animals received intra-PVT infusions of saline, tetrodotoxin (TTX; 2.5 ng, CART (0.625 µg or 2.5 µg or no injection, followed by a cocaine prime (10 mg/kg, i.p.. Animals were then tested under extinction conditions for one hour. Treatment with either TTX or CART resulted in a significant attenuation of drug-seeking behaviour following cocaine-prime, with the 2.5 µg dose of CART having the greatest effect. This effect was specific to the PVT region, as misplaced injections of both TTX and CART resulted in responding that was identical to controls. CONCLUSIONS/SIGNIFICANCE: We show for the first time that CART signaling within the PVT acts to inhibit drug-primed reinstatement of cocaine seeking behaviour, presumably by negatively modulating PVT efferents that are important for drug seeking, including the NAC, mPFC and BLA. In this way, we identify a possible target for future pharmacological interventions designed to suppress drug seeking.

  5. Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

    Science.gov (United States)

    Cho, Jin Hee; Cho, Yun Ha; Kim, Hyo Young; Cha, Seung Ha; Ryu, Hyun; Jang, Wooyoung; Shin, Kyung Ho

    2015-04-01

    Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Mephedrone does not damage dopamine nerve endings of the striatum, but enhances the neurotoxicity of methamphetamine, amphetamine, and MDMA.

    Science.gov (United States)

    Angoa-Pérez, Mariana; Kane, Michael J; Briggs, Denise I; Francescutti, Dina M; Sykes, Catherine E; Shah, Mrudang M; Thomas, David M; Kuhn, Donald M

    2013-04-01

    Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its re-uptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamine-induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20, or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (four injections of 2.5 or 5.0 mg/kg at 2 h intervals). The integrity of DA nerve endings of the striatum was assessed through measures of DA, DAT, and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and 3,4-methylenedioxymethamphetamine on DA nerve endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. As mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA nerve endings mask a potentially dangerous interaction with drugs that are often co-abused with it, leading to heightened neurotoxicity. © 2012 International Society for Neurochemistry.

  7. Acute total sleep deprivation potentiates amphetamine-induced locomotor-stimulant effects and behavioral sensitization in mice.

    Science.gov (United States)

    Saito, Luis P; Fukushiro, Daniela F; Hollais, André W; Mári-Kawamoto, Elisa; Costa, Jacqueline M; Berro, Laís F; Aramini, Tatiana C F; Wuo-Silva, Raphael; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

    2014-02-01

    It has been demonstrated that a prolonged period (48 h) of paradoxical sleep deprivation (PSD) potentiates amphetamine (AMP)-induced behavioral sensitization, an animal model of addiction-related neuroadaptations. In the present study, we examined the effects of an acute short-term deprivation of total sleep (TSD) (6h) on AMP-induced behavioral sensitization in mice and compared them to the effects of short-term PSD (6 h). Three-month-old male C57BL/6J mice underwent TSD (experiment 1-gentle handling method) or PSD (experiment 2-multiple platforms method) for 6 h. Immediately after the sleep deprivation period, mice were tested in the open field for 10 min under the effects of saline or 2.0 mg/kg AMP. Seven days later, to assess behavioral sensitization, all of the mice received a challenge injection of 2.0 mg/kg AMP and were tested in the open field for 10 min. Total, peripheral, and central locomotion, and grooming duration were measured. TSD, but not PSD, potentiated the hyperlocomotion induced by an acute injection of AMP and this effect was due to an increased locomotion in the central squares of the apparatus. Similarly, TSD facilitated the development of AMP-induced sensitization, but only in the central locomotion parameter. The data indicate that an acute period of TSD may exacerbate the behavioral effects of AMP in mice. Because sleep architecture is composed of paradoxical and slow wave sleep, and 6-h PSD had no effects on AMP-induced hyperlocomotion or sensitization, our data suggest that the deprivation of slow wave sleep plays a critical role in the mechanisms that underlie the potentiating effects of TSD on both the acute and sensitized addiction-related responses to AMP. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Memory and brain-derived neurotrophic factor after subchronic or chronic amphetamine treatment in an animal model of mania.

    Science.gov (United States)

    Fries, Gabriel R; Valvassori, Samira S; Bock, Hugo; Stertz, Laura; Magalhães, Pedro Vieira da Silva; Mariot, Edimilson; Varela, Roger B; Kauer-Sant'Anna, Marcia; Quevedo, João; Kapczinski, Flávio; Saraiva-Pereira, Maria Luiza

    2015-09-01

    Progression of bipolar disorder (BD) has been associated with cognitive impairment and changes in neuroplasticity, including a decrease in serum brain-derived neurotrophic factor (BDNF). However, no study could examine BDNF levels directly in different brain regions after repeated mood episodes to date. The proposed animal model was designed to mimic several manic episodes and evaluate whether the performance in memory tasks and BDNF levels in hippocampus, prefrontal cortex, and amygdala would change after repeated amphetamine (AMPH) exposure. Adult male Wistar rats were divided into subchronic (AMPH for 7 days) and chronic groups (35 days), mimicking manic episodes at early and late stages of BD, respectively. After open field habituation or inhibitory avoidance test, rats were killed, brain regions were isolated, and BDNF mRNA and protein levels were measured by quantitative real-time PCR and ELISA, respectively. AMPH impaired habituation memory in both subchronic and chronic groups, and the impairment was worse in the chronic group. This was accompanied by increased Bdnf mRNA levels in the prefrontal cortex and amygdala region, as well as reduced BDNF protein in the hippocampus. In the inhibitory avoidance, AMPH significantly decreased the change from training to test when compared to saline. No difference was observed between subchronic and chronic groups, although chronically AMPH-treated rats presented increased Bdnf mRNA levels and decreased protein levels in hippocampus when compared to the subchronic group. Our results suggest that the cognitive impairment related to BD neuroprogression may be associated with BDNF alterations in hippocampus, prefrontal cortex, and amygdala. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Cocaine- and amphetamine-regulated transcript and calcium binding proteins immunoreactivity in the subicular complex of the guinea pig.

    Science.gov (United States)

    Wasilewska, Barbara; Najdzion, Janusz; Równiak, Maciej; Bogus-Nowakowska, Krystyna; Hermanowicz, Beata; Kolenkiewicz, Małgorzata; Żakowski, Witold; Robak, Anna

    2016-03-01

    In this study we present the distribution and colocalization pattern of cocaine- and amphetamine-regulated transcript (CART) and three calcium-binding proteins: calbindin (CB), calretinin (CR) and parvalbumin (PV) in the subicular complex (SC) of the guinea pig. The subiculum (S) and presubiculum (PrS) showed higher CART-immunoreactivity (-IR) than the parasubiculum (PaS) as far as the perikarya and neuropil were concerned. CART- IR cells were mainly observed in the pyramidal layer and occasionally in the molecular layer of the S. In the PrS and PaS, single CART-IR perikarya were dispersed, however with a tendency to be found only in superficial layers. CART-IR fibers were observed throughout the entire guinea pig subicular neuropil. Double-labeling immunofluorescence showed that CART-IR perikarya, as well as fibers, did not stain positively for any of the three CaBPs. CART-IR fibers were only located near the CB-, CR-, PV-IR perikarya, whereas CART-IR fibers occasionally intersected fibers containing one of the three CaBPs. The distribution pattern of CART was more similar to that of CB and CR than to that of PV. In the PrS, the CART, CB and CR immunoreactivity showed a laminar distribution pattern. In the case of the PV, this distribution pattern in the PrS was much less prominent than that of CART, CB and CR. We conclude that a heterogeneous distribution of the CART and CaBPs in the guinea pig SC is in keeping with findings from other mammals, however species specific differences have been observed. Copyright © 2015 Elsevier GmbH. All rights reserved.

  10. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids

    Science.gov (United States)

    Covey, Dan P.; Bunner, Kendra D.; Schuweiler, Douglas R.; Cheer, Joseph F.; Garris, Paul A.

    2018-01-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  11. Direct and Systemic Administration of a CNS-Permeant Tamoxifen Analog Reduces Amphetamine-Induced Dopamine Release and Reinforcing Effects.

    Science.gov (United States)

    Carpenter, Colleen; Zestos, Alexander G; Altshuler, Rachel; Sorenson, Roderick J; Guptaroy, Bipasha; Showalter, Hollis D; Kennedy, Robert T; Jutkiewicz, Emily; Gnegy, Margaret E

    2017-09-01

    Amphetamines (AMPHs) are globally abused. With no effective treatment for AMPH addiction to date, there is urgent need for the identification of druggable targets that mediate the reinforcing action of this stimulant class. AMPH-stimulated dopamine efflux is modulated by protein kinase C (PKC) activation. Inhibition of PKC reduces AMPH-stimulated dopamine efflux and locomotor activity. The only known CNS-permeant PKC inhibitor is the selective estrogen receptor modulator tamoxifen. In this study, we demonstrate that a tamoxifen analog, 6c, which more potently inhibits PKC than tamoxifen but lacks affinity for the estrogen receptor, reduces AMPH-stimulated increases in extracellular dopamine and reinforcement-related behavior. In rat striatal synaptosomes, 6c was almost fivefold more potent at inhibiting AMPH-stimulated dopamine efflux than [ 3 H]dopamine uptake through the dopamine transporter (DAT). The compound did not compete with [ 3 H]WIN 35,428 binding or affect surface DAT levels. Using microdialysis, direct accumbal administration of 1 μM 6c reduced dopamine overflow in freely moving rats. Using LC-MS, we demonstrate that 6c is CNS-permeant. Systemic treatment of rats with 6 mg/kg 6c either simultaneously or 18 h prior to systemic AMPH administration reduced both AMPH-stimulated dopamine overflow and AMPH-induced locomotor effects. Finally, 18 h pretreatment of rats with 6 mg/kg 6c s.c. reduces AMPH-self administration but not food self-administration. These results demonstrate the utility of tamoxifen analogs in reducing AMPH effects on dopamine and reinforcement-related behaviors and suggest a new avenue of development for therapeutics to reduce AMPH abuse.

  12. Endoplasmic reticulum stress responses differ in meninges and associated vasculature, striatum, and parietal cortex after a neurotoxic amphetamine exposure.

    Science.gov (United States)

    Thomas, Monzy; George, Nysia I; Saini, Upasana T; Patterson, Tucker A; Hanig, Joseph P; Bowyer, John F

    2010-08-01

    Amphetamine (AMPH) is used to treat attention deficit and hyperactivity disorders, but it can produce neurotoxicity and adverse vascular effects at high doses. The endoplasmic reticulum (ER) stress response (ERSR) entails the unfolded protein response, which helps to avoid or minimize ER dysfunction. ERSR is often associated with toxicities resulting from the accumulation of unfolded or misfolded proteins and has been associated with methamphetamine toxicity in the striatum. The present study evaluates the effect of AMPH on several ERSR elements in meninges and associated vasculature (MAV), parietal cortex, and striatum. Adult, male Sprague-Dawley rats were exposed to saline, environmentally induced hyperthermia (EIH) or four consecutive doses of AMPH that produce hyperthermia. Expression changes (mRNA and protein levels) of key ERSR-related genes in MAV, striatum, and parietal cortex at 3 h or 1 day postdosing were monitored. AMPH increased the expression of some ERSR-related genes in all tissues. Atf4 (activating transcription factor 4, an indicator of Perk pathway activation), Hspa5/Grp78 (Glucose regulated protein 78, master regulator of ERSR), Pdia4 (protein disulfide isomerase, protein-folding enzyme), and Nfkb1 (nuclear factor of kappa b, ERSR sensor) mRNA increased significantly in MAV and parietal cortex 3 h after AMPH. In striatum, Atf4 and Hspa5/Grp78 mRNA significantly increased 3 h after AMPH, but Pdia4 and Nfkb11 did not. Thus, AMPH caused a robust activation of the Perk pathway in all tissues, but significant Ire1 pathway activation occurred only after AMPH treatment in the parietal cortex and striatum. Ddit3/Chop, a downstream effector of the ERSR pathway related to the neurotoxicity, was only increased in striatum and parietal cortex. Conversely, Pdia4, an enzyme protective in the ERSR, was only increased in MAV. The overall ERSR manifestation varied significantly between MAV, striatum, and parietal cortex after a neurotoxic exposure to AMPH.

  13. Synergistic effect of CART (cocaine- and amphetamine-regulated transcript peptide and cholecystokinin on food intake regulation in lean mice

    Directory of Open Access Journals (Sweden)

    Kiss Alexander

    2008-10-01

    Full Text Available Abstract Background CART (cocaine- and amphetamine-regulated transcript peptide and cholecystokinin (CCK are neuromodulators involved in feeding behavior. This study is based on previously found synergistic effect of leptin and CCK on food intake and our hypothesis on a co-operation of the CART peptide and CCK in food intake regulation and Fos activation in their common targets, the nucleus tractus solitarii of the brainstem (NTS, the paraventricular nucleus (PVN, and the dorsomedial nucleus (DMH of the hypothalamus. Results In fasted C57BL/6 mice, the anorexigenic effect of CART(61-102 in the doses of 0.1 or 0.5 μg/mouse was significantly enhanced by low doses of CCK-8 of 0.4 or 4 μg/kg, while 1 mg/kg dose of CCK-A receptor antagonist devazepide blocked the effect of CART(61-102 on food intake. After simultaneous administration of 0.1 μg/mouse CART(61-102 and of 4 μg/kg of CCK-8, the number of Fos-positive neurons in NTS, PVN, and DMH was significantly higher than after administration of each particular peptide. Besides, CART(61-102 and CCK-8 showed an additive effect on inhibition of the locomotor activity of mice in an open field test. Conclusion The synergistic and long-lasting effect of the CART peptide and CCK on food intake and their additive effect on Fos immunoreactivity in their common targets suggest a co-operative action of CART peptide and CCK which could be related to synergistic effect of leptin on CCK satiety.

  14. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

    Science.gov (United States)

    Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

    2016-06-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  15. Comparison of Caffeine and d-amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine.

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    Lane, Scott D; Green, Charles E; Schmitz, Joy M; Rathnayaka, Nuvan; Fang, Wendy B; Ferré, Sergi; Moeller, F Gerard

    2014-01-01

    Due to indirect modulation of dopamine transmission, adenosine receptor antagonists may be useful in either treating cocaine use or improving disrupted cognitive-behavioral functions associated with chronic cocaine use. To compare and contrast the stimulant effects of adenosine antagonism to direct dopamine stimulation, we administered 150 mg and 300 mg caffeine, 20 mg amphetamine, and placebo to cocaine-dependent vs. healthy control subjects, matched on moderate caffeine use. Data were obtained on measures of cardiovascular effects, subjective drug effects (ARCI, VAS, DEQ), and a probabilistic reward-learning task sensitive to dopamine modulation. Levels of salivary caffeine and the primary caffeine metabolite paraxanthine were obtained on placebo and caffeine dosing days. Cardiovascular results revealed main effects of dose for diastolic blood pressure and heart rate; follow up tests showed that controls were most sensitive to 300 mg caffeine and 20 mg amphetamine; cocaine-dependent subjects were sensitive only to 300 mg caffeine. Subjective effects results revealed dose × time and dose × group interactions on the ARCI A, ARCI LSD, and VAS 'elated' scales; follow up tests did not show systematic differences between groups with regard to caffeine or d-amphetamine. Large between-group differences in salivary paraxanthine (but not salivary caffeine) levels were obtained under both caffeine doses. The cocaine-dependent group expressed significantly higher paraxanthine levels than controls under 150 mg and 3-4 fold greater levels under 300 mg at 90 min and 150 min post caffeine dose. However, these differences also covaried with cigarette smoking status (not balanced between groups), and nicotine smoking is known to alter caffeine/paraxanthine metabolism via cytochrome P450 enzymes. These preliminary data raise the possibility that adenosine antagonists may affect cocaine-dependent and non-dependent subjects differently. In conjunction with previous preclinical and

  16. Differential effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone) in rats trained to discriminate MDMA or a d-amphetamine + MDMA mixture.

    Science.gov (United States)

    Harvey, Eric L; Baker, Lisa E

    2016-02-01

    Recent reports on the abuse of novel synthetic cathinone derivatives call attention to serious public health risks of these substances. In response to this concern, a growing body of preclinical research has characterized the psychopharmacology of these substances, particularly mephedrone (MEPH) or methylenedioxypyrovalerone (MDPV), noting their similarities to 3,4-methylenedioxymethamphetamine (MDMA) and cocaine. Few studies have utilized drug discrimination methodology to characterize the psychopharmacological properties of these substances. The present study employed a rodent drug discrimination assay to further characterize the stimulus effects of MEPH and MDPV in comparison to MDMA and to a drug mixture comprised of d-amphetamine and MDMA. Eight male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg MDMA, and eight rats were trained to discriminate a mixture of 1.5 mg/kg MDMA and 0.5 mg/kg d-amphetamine (MDMA + AMPH) from vehicle. Substitution tests were conducted with MDMA, d-amphetamine, MDPV, MEPH, and cocaine. Dose-response curves generated with MDMA and MEPH were comparable between training groups. In contrast, AMPH, MDPV, and cocaine produced only partial substitution in animals trained to discriminate MDMA but produced full substitution in animals trained to discriminate the MDMA + AMPH mixture. These findings indicate that MDPV's effects may be more similar to those of traditional psychostimulants, whereas MEPH exerts stimulus effects more similar to those of MDMA. Additional experiments with selective DA and 5-hydroxytryptamine (5-HT) receptor antagonists are required to further elucidate specific receptor mechanisms mediating the discriminative stimulus effects of MDPV and mephedrone.

  17. Brain pattern of histone H3 phosphorylation after acute amphetamine administration: its relationship to brain c-fos induction is strongly dependent on the particular brain area.

    Science.gov (United States)

    Rotllant, David; Armario, Antonio

    2012-02-01

    Recent evidence strongly suggests a critical role of chromatin remodelling in the acute and chronic effects of addictive drugs. We reasoned that Immunohistochemical detection of certain histone modifications may be a more specific tool than induction of immediate early genes (i.e. c-fos) to detect brain areas and neurons that are critical for the action of addictive drugs. Thus, in the present work we studied in adult male rats the effects of a high dose of amphetamine on brain pattern of histone H3 phosphorylation in serine 10 (pH3S(10)) and c-fos expression. We firstly observed that amphetamine-induced an increase in the number of pH3S(10) positive neurons in a restricted number of brain areas, with maximum levels at 30 min after the drug administration that declined at 90 min in most areas. In a second experiment we studied colocalization of pH3S(10) immunoreactivity (pH3S(10)-IR) and c-fos expression. Amphetamine increased c-fos expression in medial prefrontal cortex (mPFC), dorsal striatum, nucleus accumbens (Acb), major Island of Calleja (ICjM), central amygdala (CeA), bed nucleus of stria terminalis lateral dorsal (BSTld) and paraventricular nucleus of the hypothalamus (PVN). Whereas no evidence for increase in pH3S(10) positive neurons was found in the mPFC and the PVN, in the striatum and the Acb basically all pH3S(10) positive neurons showed colocalization with c-fos. In ICjM, CeA and BSTld a notable degree of colocalization was found, but an important number of neurons expressing c-fos were negative for pH3S(10). The present results give support to the hypothesis that amphetamine-induced pH3S(10)-IR showed a more restricted pattern than brain c-fos induction, being this difference strongly dependent on the particular brain area studied. It is likely that those nuclei and neurons showing pH3S(10)-IR are more specifically associated to important effects of the drug, including neural plasticity. This article is part of a Special Issue entitled 'Post

  18. Poor sensitization of 50-kHz vocalization response to amphetamine predicts rat susceptibility to self-administration of the drug

    OpenAIRE

    Taracha, Ewa; Kaniuga, Ewelina; Wyszogrodzka, Edyta; P?a?nik, Adam; Stefa?ski, Roman; Chrapusta, Stanis?aw J.

    2016-01-01

    Rationale Our previous studies showed promise for using sensitization of the frequency-modulated 50-kHz vocalization response to amphetamine (AMPH) as an index of rat vulnerability to AMPH addiction. Objective This study aimed to test the utility of sensitizing frequency-modulated (FM) 50-kHz vocalization in the AMPH self-administration paradigm as well as the ability of N-acetylcysteine to prevent self-administration relapse. Methods Rats were subjected to the so-called two-injection protoco...

  19. Amphetamine-type stimulants and HIV infection among men who have sex with men: implications on HIV research and prevention from a systematic review and meta-analysis

    OpenAIRE

    Nga Thi Thu Vu; Lisa Maher; Iryna Zablotska

    2015-01-01

    Introduction: HIV infections and the use of amphetamine-type stimulants (ATS) among men who have sex with men (MSM) have been increasing internationally, but the role of ATS use as a co-factor for HIV infection remains unclear. We aimed to summarize the association between ATS use and HIV infection among MSM. Methods: We conducted a systematic search of MEDLINE, EMBASE, GLOBAL HEALTH and PsycINFO for relevant English, peer-reviewed articles of quantitative studies published between 1980 and 2...

  20. Effects of muscimol, amphetamine, and DAMGO injected into the nucleus accumbens shell on food-reinforced lever pressing by undeprived rats.

    Science.gov (United States)

    Stratford, Thomas R; Wirtshafter, David

    2012-05-01

    Previous studies have shown that large increases in food intake in nondeprived animals can be induced by injections of both the GABA(A) agonist muscimol and the μ-opioid agonist DAMGO into the nucleus accumbens shell (AcbSh), while injections of the catecholamine agonist amphetamine have little effect. In the current study we examined whether injections of these drugs are able to increase food-reinforced lever pressing in nondeprived rats. Twelve subjects were trained to lever press on a continuous reinforcement schedule while food deprived and were then tested after being placed back on ad libitum feeding. Under these conditions, responding was markedly increased by injections of either muscimol or DAMGO, although the onset of the effects of the latter drug was delayed by 30-40 min. In contrast, amphetamine injections failed to increase reinforced lever pressing, although they did enhance responding on a non-reinforced lever, presumably reflecting alterations in behavioral activation. These results demonstrate that stimulation of GABA(A) and μ-opioid receptors within the AcbSh is able to promote not only food intake, but also food-directed operant behavior. In contrast, stimulation of AcbSh dopamine receptors may enhance behavioral arousal, but does not appear to specifically potentiate behaviors directed toward food procurement. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Solid-phase extraction followed by dispersive liquid-liquid microextraction for the sensitive determination of ecstasy compounds and amphetamines in biological samples

    Directory of Open Access Journals (Sweden)

    H. A. Mashayekhi

    2014-09-01

    Full Text Available A novel approach for the determination of ecstasy and amphetamines (3,4-methylenedioxymethylamphetamine (MDMA, Ecstasy, 3,4-methylenedioxyamphetamine (MDA, 3,4-methylenedioxyethylamphetamine (MDEA and 3,4-methylenedioxypropylamphetamine (MDPA in biological samples is presented. The analytes were extracted from the matrix and transferred to a small volume of a high density, water insoluble solvent using solid-phase extraction (SPE followed by dispersive liquid-liquid microextraction (DLLME. This combination not only resulted in a high enrichment factor, but also it could be used in complex matrices (biological samples. Some important extraction parameters, such as sample solution flow rate, sample pH, type and volume of extraction and disperser solvents as well as the salt addition, were studied and optimized. Under the optimized conditions, the calibration graphs were linear in the range of 0.5-500 µg L-1 and 1.0-500 µg L-1 with detection limits in the range of 0.1-0.3 µg L-1 and 0.2-0.7 µg L-1 in urine and plasma samples, respectively. The results showed that SPE-DLLME is a suitable method for the determination of ecstasy components and amphetamines in biological and water samples. DOI: http://dx.doi.org/10.4314/bcse.v28i3.3

  2. Monolithic silica spin column extraction and simultaneous derivatization of amphetamines and 3,4-methylenedioxyamphetamines in human urine for gas chromatographic-mass spectrometric detection

    International Nuclear Information System (INIS)

    Nakamoto, Akihiro; Nishida, Manami; Saito, Takeshi; Kishiyama, Izumi; Miyazaki, Shota; Murakami, Katsunori; Nagao, Masataka; Namura, Akira

    2010-01-01

    A simple, sensitive, and specific method with gas chromatography-mass spectrometry was developed for simultaneous extraction and derivatization of amphetamines (APs) and 3,4-methylenedioxyamphetamines (MDAs) in human urine by using a monolithic silica spin column. All the procedures, such as sample loading, washing, and elution were performed by centrifugation. APs and MDAs in urine were adsorbed on the monolithic silica and derivatized with propyl chloroformate in the column. Methamphetamine-d 5 was used as an internal standard. The linear ranges were 0.01-5.0 μg mL -1 for methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) and 0.02-5.0 μg mL -1 for amphetamine (AP) and 3,4-methylenedioxyamphetamine (MDA) (coefficient of correlation ≥0.995). The recovery of APs and MDAs in urine was 84-94%, and the relative standard deviation of the intra- and interday reproducibility for urine samples containing 0.1, 1.0, and 4.0 μg mL -1 of APs and MDAs ranged from 1.4% to 13.6%. The lowest detection limit (signal-to-noise ratio ≥ 3) in urine was 5 ng mL -1 for MA and MDMA and 10 ng mL -1 for AP and MDA. The proposed method can be used to perform simultaneous extraction and derivatization on spin columns that have been loaded with a small quantity of solvent by using centrifugation.

  3. Olanzapine and haloperidol for the treatment of acute symptoms of mental disorders induced by amphetamine-type stimulants: A randomized controlled trial.

    Science.gov (United States)

    Xue, Xiaobin; Song, Yun; Yu, Xiaojie; Fan, Qiang; Tang, Jiyou; Chen, Xu

    2018-02-01

    This study aimed to compare olanzapine and haloperidol efficacies in the treatment of acute psychiatric symptoms due to amphetamine-type stimulants (ATSs). The Zelen II design method was used; 124 patients with acute mental disorders due to amphetamine were randomly divided into olanzapine group (n = 63) and haloperidol group (n = 61). Then, a 4-week open-label medical therapy was performed. Clinical Global Impression Scale Item 2 was employed to evaluate the onset time; meanwhile, Brief Psychiatric Rating Scale (BPRS) was used at baseline and at posttreatment weeks 1, 2, and 4. Moreover, adverse reactions during the treatment were recorded. Onset time in the olanzapine group was significantly earlier than in the haloperidol group; BPRS scores in the olanzapine group were significantly lower than haloperidol group values at 1 and 2 weeks of treatment. The overall effective rates had no statistically significant difference. Short-term olanzapine and haloperidol treatments had equivalent efficacies in the treatment of acute symptoms of mental disorders due to ATSs; however, olanzapine administration resulted in relatively earlier disease onset, with less adverse reactions.

  4. An amphetamine isomer whose efficacy and safety in humans has never been studied, β-methylphenylethylamine (BMPEA), is found in multiple dietary supplements.

    Science.gov (United States)

    Cohen, Pieter A; Bloszies, Clayton; Yee, Caleb; Gerona, Roy

    2016-01-01

    The amphetamine isomer β-methylphenylethylamine (BMPEA) was first synthesized in the early 1930s, but its efficacy and safety in humans has not been studied. Recently, the United States Food and Drug Administration (FDA) detected BMPEA in dietary supplements labelled as containing Acacia rigidula. Over a year after the FDA reported its findings, we analyzed Acacia rigidula dietary supplements to determine if BMPEA had been removed. Supplements were analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry. Diluted methanolic extract from each supplement was run three times and each data set obtained was analyzed using Agilent MassHunter Qualitative Analysis. The presence of BMPEA was confirmed by accurate mass, retention time and mass spectra match against a reference standard. Quantification of BMPEA was determined using an eight-point calibration curve of spiked standard to a matrix blank. Twenty-one brands of Acacia rigidula supplements were analyzed. More than half (11/21; 52.4%) of the Acacia rigidula supplement brands contained BMPEA. The stimulant was present at quantities such that consumers following recommended maximum daily servings would consume a maximum of 93.7 mg of BMPEA per day. Consumers of Acacia rigidula supplements may be exposed to pharmacological dosages of an amphetamine isomer that lacks evidence of safety in humans. The FDA should immediately warn consumers about BMPEA and take aggressive enforcement action to eliminate BMPEA in dietary supplements. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  5. The effect of the substituted amphetamines, 2.4-methylenedioxymethamphetamine (MDMA) and P-methoxyamphetamine (PMA), on platelet aggregation

    International Nuclear Information System (INIS)

    Sluggett, A.J.; Irvine, R.J.; Bochner, F.; Rodgers, S.; Lloyd, J.V.

    2001-01-01

    Full text: Illicit substituted amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA) and p-methoxyamphetamine (PMA) can cause severe toxicity. Disruption of normal coagulation mechanisms have been observed in most fatal cases. However, the precise mechanisms underlying these events are not clearly understood. MDMA and PMA are known to inhibit serotonin transporter function in the central nervous system (Daws et al 2000) and platelet serotonin transporter sites (Rudnick and Wall 1992). Serotonin is in high concentrations in platelets and activation of 5HT 2 receptors on the platelet surface potentiates aggregation of platelets. Therefore, we postulated that MDMA and PMA may have effects on coagulation via inhibition of normal platelet function. Human citrated platelets were incubated in the presence of MDMA (43- 435μM) or PMA (49-498μM) and their aggregator y response to a critical dose of adenosine diphosphate (ADP) determined. These responses were compared to the serotonin reuptake inhibitor fluoxetine (13-130μM). All 3 compounds were found to inhibit platelet aggregation. The IC50s for % aggregation at 5 minutes were MDMA 197μM ± 63μM PMA 344μM ±76μM and fluoxetine 24μM ±1 1μM (n=4). The effect of these drugs on the uptake of 14 C-5HT (0.9 μM /ml) into platelets was also determined and the IC50s observed were MDMA 62.3 μM ±11μM , PMA 24μM ±6μM and fluoxetine 2.5μM ± 0.6μM (n=4). The in vitro effects of MDMA and PMA on aggregation and uptake observed here are close to concentrations reported to have occurred in human fatalities. Therefore it is possible that direct effects of these drugs on coagulation mechanisms may contribute to the toxicity of these compounds. Copyright (2001) Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

  6. Distribution of cocaine- and amphetamine-regulated transcript in the hippocampal formation of the guinea pig and domestic pig.

    Science.gov (United States)

    Kolenkiewicz, M; Robak, A; Równiak, M; Bogus-Nowakowska, K; Całka, J; Majewski, M

    2009-02-01

    This study provides a detailed description concerning the distribution of cocaineand amphetamine-regulated transcript (CART) subunits - CART(61-102) and rhCART(28-116) - in the hippocampal formation (HF) of the guinea pig and domestic pig, focussing on the dentate gyrus (DG) and hippocampus proper (HP). Although in both studied species CART-immunoreactive (CART-IR) neuronal somata and processes were present generally in the same layers, some species-specific differences were still found. In the granular layer (GL) of both species, the ovalshaped neurons and some thick varicose fibres were encountered. In the guinea pig there was an immunoreactive "band of dots", probably representing crosssectioned terminals within the DG molecular layer (MOL), whereas in the domestic pig, some varicose fibres were detected, thus suggesting a different orientation of, at least, some nerve terminals. Furthermore, some CART-positive cells and fibres were observed in the hilus (HL) of the guinea pig, whereas in the analogical part of the domestic pig only nerve terminals were labelled. In both species, in the pyramidal layer (PL) of the hippocampus proper, CART-IR triangular somata were observed in the CA3 sector, as well as some positive processes in MOL; however, a few immunoreactive perikarya were found only in the CA1 sector of the guinea pig. As regards the localization patterns of two isoforms of CART in the guinea pig, both peptide fragments were present simultaneously in each of the labelled neurons or fibres, whereas in the domestic pig three types of fibres may be distinguished within the area of the DG. In the hilus and MOL of the dentate gyrus, there were fibres expressing both isoforms of CART in their whole length (fibres of the first type). Fibres of the second type (in GL) coexpressed both peptides only on their short segments, and the last ones (in MOL) expressed solely rhCART(28-116). These results indicate that the distribution of the two CART isoforms are

  7. HIV treatment cascade among female entertainment and sex workers in Cambodia: impact of amphetamine use and an HIV prevention program.

    Science.gov (United States)

    Muth, Sokunny; Len, Aynar; Evans, Jennifer L; Phou, Maly; Chhit, Sophal; Neak, Yuthea; Ngak, Song; Stein, Ellen S; Carrico, Adam W; Maher, Lisa; Page, Kimberly

    2017-09-05

    HIV prevalence remains high in Cambodia among female entertainment and sex workers (FESW), and amphetamine-type stimulant (ATS) use significantly increases risk of infection. A successful continuum of care (CoC) is key to effective clinical care and prevention. This study aimed to describe the HIV CoC in HIV-positive FESW. We examined CoC outcomes among HIV-positive FESW participating in the Cambodia Integrated HIV and Drug Prevention Implementation (CIPI) study, being implemented in ten provinces. CIPI is a trial aimed at reducing ATS use concomitant with the SMARTgirl HIV prevention program. From 2013 to 2016, 1198 FESW ≥ 18 years old who reported multiple sex partners and/or transactional sex were recruited. We identified 88 HIV-positive women at baseline. We described linkage to care as 12-month retention and viral suppression (HIV-positive women was 32 years [interquartile range (IQR) 28, 35]; 50% were working in entertainment venues and 50% as freelance sex workers; 70% reported SMARTgirl membership. In the past 3 months, women reported a median of 15 sex partners, 38% reported unprotected sex, and 55% reported using ATS. Overall, 88% were receiving HIV care, 83% were on antiretroviral therapy, 39% were retained in care at 12 months, and 23% were virally suppressed. SMARTgirl membership was independently associated with fourfold greater odds of 12-month retention in care (AOR = 4.16, 95% CI 1.38, 12.56). Those at high risk for an ATS use disorder had 91% lower odds of 12-month retention in care (AOR = 0.09, 95% CI 0.01, 0.72). Viral suppression was independently associated with SMARTgirl membership, older age, reporting of STI symptoms, worse symptoms of psychological distress, and greater numbers of sex partners. This is the first study to characterize the HIV CoC in Cambodian FESW. While most women were successfully linked to HIV care, retention and viral suppression were low. Tailored programs like SMARTgirl, targeting the broader population of

  8. Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Thanos, P.K.; Bermeo, C.; Rubinstein, M.; Suchland, K.L.; Wang, G.-J.; Grandy, D.K.; Volkow, N.D.

    2010-05-01

    Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs

  9. Amphetamine-type stimulants and HIV infection among men who have sex with men: implications on HIV research and prevention from a systematic review and meta-analysis

    Science.gov (United States)

    Thu Vu, Nga Thi; Maher, Lisa; Zablotska, Iryna

    2015-01-01

    Introduction HIV infections and the use of amphetamine-type stimulants (ATS) among men who have sex with men (MSM) have been increasing internationally, but the role of ATS use as a co-factor for HIV infection remains unclear. We aimed to summarize the association between ATS use and HIV infection among MSM. Methods We conducted a systematic search of MEDLINE, EMBASE, GLOBAL HEALTH and PsycINFO for relevant English, peer-reviewed articles of quantitative studies published between 1980 and 25 April 2013. Pooled estimates of the association – prevalence rate ratios (PRR, cross-sectional studies), odds ratio (OR, case-control studies) and hazard ratio (HR, longitudinal studies), with 95% Confidence Intervals (CI) – were calculated using random-effects models stratified by study design and ATS group (meth/amphetamines vs. ecstasy). We assessed the existence of publication bias in funnel plots and checked for sources of heterogeneity using meta-regression and subgroup analysis. Results We identified 6710 article titles, screened 1716 abstracts and reviewed 267 full text articles. A total of 35 publications were eligible for data abstraction and meta-analysis, resulting in 56 records of ATS use. Most studies (31/35) were conducted in high-income countries. Published studies used different research designs, samples and measures of ATS use. The pooled association between meth/amphetamine use and HIV infection was statistically significant in all three designs (PRR=1.86; 95% CI: 1.57–2.17; OR=2.73; 95% CI: 2.16–3.46 and HR=3.43; 95% CI: 2.98–3.95, respectively, for cross-sectional, case-control and longitudinal studies). Ecstasy use was not associated with HIV infection in cross-sectional studies (PRR=1.15; 95% CI: 0.88–1.49; OR=3.04; 95% CI: 1.29–7.18 and HR=2.48; 95% CI: 1.42–4.35, respectively, for cross-sectional, case-control and longitudinal studies). Results in cross-sectional studies were highly heterogeneous due to issues with ATS measurement and

  10. The effects of d-lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM) and d-amphetamine on operant responding in control and 6-hydroxydopamine-treated rats.

    Science.gov (United States)

    Commissaris, R; Lyness, W H; Cordon, J J; Moore, K E; Rech, R H

    1980-11-01

    The purpose of the present study was to determine the role of central catecholaminergic neuronal systems in the effects of LSD, DOM and d-amphetamine on fixed ratio (FR) operant responding in rats. Food-deprived male rats were trained to press a bar for food reinforcement on a FR-40 schedule. Control responding on this schedule is characterized by a rapid, constant rate of responding (approximately 100 responses/min) throughout a 40 min test session. LSD and DOM, as with other hallucinogens, produced dose-dependent periods of nonresponding or "pausing," followed by reinstatement of responding at or near the control rate. Administration of the non-hallucinogen, d-amphetamine, did not produce "pausing," but caused the response rate to slow and become erratic. In animals pretreated intraventricularly with 6-hydroxydopamine (6-OHDA; 200 micrograms/10 microliter X 2), the response to LSD and DOM was unchanged, while the response to d-amphetamine was significantly diminished. The neurotoxin significantly decreased brain catecholamines to less than 25 percent of control in al regions examined, without altering 5-HT concentrations in these same regions. These data demonstrate that the effects of LSD and DOM on FR-40 responding are quite different from those of d-amphetamine, and that this difference may be due to the extent of catecholamine involvement in the effects of these agents.

  11. Amphetamine-Type-Stimulants (ATS) Use and Homosexuality-Related Enacted Stigma Are Associated With Depression Among Men Who Have Sex With Men (MSM) in Two Major Cities in Vietnam in 2014

    NARCIS (Netherlands)

    Vu, Nga Thi Thu; Holt, Martin; Phan, Huong Thi Thu; La, Lan Thi; Tran, Gioi Minh; Doan, Tung Thanh; Nguyen, Trang Nhu Nguyen; de Wit, John

    2017-01-01

    BACKGROUND: Men who have sex with men (MSM) are disproportionately affected by mental health concerns, including depression. Amphetamine-type-stimulants (ATS) use and homosexuality-related stigma and discrimination have been found associated with depression among MSM. OBJECTIVES: To assess the

  12. CA2+/CALMODULIN-DEPENDENT KINASE II- ASSOCIATES WITH THE C TERMINUS OF THE DOPAMINE TRANSPORTER AND INCREASES AMPHETAMINE-INDUCED DOPAMINE EFFLUX VIA PHOSPHORYLATION OF N-TERMINAL SERINES

    DEFF Research Database (Denmark)

    Fog, Jacob; Khoshbouei, H; Holy, M

    The dopamine transporter(DAT) plays a key role in clearing extracellular dopamine(DA) from the synapse. Moreover DAT is a target for the action of widely abused psychostimulants such as cocaine and amphetamine(AMPH). AMPH is a substrate for the DAT and promotes the reversal of transport and thus...

  13. The effects of d-amphetamine on extrastriatal dopamine D{sub 2}/D{sub 3} receptors: a randomized, double-blind, placebo-controlled PET study with [{sup 11}C]FLB 457 in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Aalto, Sargo [University of Turku, Turku PET Centre, Turku (Finland); Aabo Akademi University, Department of Psychology, Turku (Finland); Hirvonen, Jussi; Kajander, Jaana; Naagren, Kjell; Rinne, Juha O. [University of Turku, Turku PET Centre, Turku (Finland); Kaasinen, Valtteri [University of Turku, Department of Neurology, P.O. Box 52, Turku (Finland); Hagelberg, Nora [University of Turku, Turku PET Centre, Turku (Finland); Turku University Central Hospital, Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku (Finland); Seppaelae, Timo [Drug Research Unit, National Public Health Institute, Helsinki (Finland); Scheinin, Harry [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, Turku (Finland); Hietala, Jarmo [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Department of Psychiatry, Turku (Finland)

    2009-03-15

    The dopamine D{sub 2}/D{sub 3} receptor ligand [{sup 11}C]FLB 457 and PET enable quantification of low-density extrastriatal D{sub 2}/D{sub 3} receptors, but it is uncertain whether [{sup 11}C]FLB 457 can be used for measuring extrastriatal dopamine release. We studied the effects of d-amphetamine (0.3 mg/kg i.v.) on extrastriatal [{sup 11}C]FLB 457 binding potential (BP{sub ND}) in a randomized, double-blind, placebo-controlled study including 24 healthy volunteers. The effects of d-amphetamine on [{sup 11}C]FLB 457 BP{sub ND} and distribution volume (V{sub T}) in the frontal cortex were not different from those of placebo. Small decreases in [{sup 11}C]FLB 457 BP{sub ND} were observed only in the posterior cingulate and hippocampus. The regional changes in [{sup 11}C]FLB 457 BP{sub ND} did not correlate with d-amphetamine-induced changes in subjective ratings of euphoria. This placebo-controlled study showed that d-amphetamine does not induce marked changes in measures of extrastriatal dopamine D{sub 2}/D{sub 3} receptor binding. Our results indicate that [{sup 11}C]FLB 457 PET is not a useful method for measuring extrastriatal dopamine release in humans. (orig.)

  14. Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4- methylenedioxymethamphetamine ("Ecstasy").

    Science.gov (United States)

    Taylor, J R; Jentsch, J D

    2001-07-15

    Psychomotor stimulant drugs can produce long-lasting changes in neurochemistry and behavior after multiple doses. In particular, neuroadaptations within corticolimbic brain structures that mediate incentive learning and motivated behavior have been demonstrated after chronic exposure to cocaine, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). As stimulus-reward learning is likely relevant to addictive behavior (i.e., augmented conditioned reward and stimulus control of behavior), we have investigated whether prior repeated administration of psychomotor stimulant drugs (of abuse, including cocaine, d-amphetamine, or MDMA, would affect the acquisition of Pavlovian approach behavior. Water-deprived rats were tested for the acquisition of Pavlovian approach behavior after 5 days treatment with cocaine (15-20 mg/kg once or twice daily), d-amphetamine (2.5 mg/kg once or twice daily), or MDMA (2.5 mg/kg twice daily) followed by a 7-day, drug-free period. Prior repeated treatment with cocaine or d-amphetamine produced a significant enhancement of acquisition of Pavlovian approach behavior, indicating accelerated stimulus-reward learning, whereas MDMA administration produced increased inappropriate responding, indicating impulsivity. Abnormal drug-induced approach behavior was found to persist throughout the testing period. These studies demonstrate that psychomotor stimulant-induced sensitization can produce long-term alterations in stimulus-reward learning and impulse control that may contribute to the compulsive drug taking that typifies addiction.

  15. Dextroamphetamine and Amphetamine

    Science.gov (United States)

    ... one else can take it accidentally or on purpose. Keep track of how many tablets or capsules ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  16. Hair analysis for drugs of abuse. XIII. Effect of structural factors on incorporation of drugs into hair: the incorporation rates of amphetamine analogs.

    Science.gov (United States)

    Nakahara, Y; Kikura, R

    1996-01-01

    In order to clarify the incorporation mechanism of drugs from blood into hair, seven effects of structural factors on the incorporation rate (ICR) were studied using 32 amphetamine analogs: (1) effect of a straight chained N-alkyl group; (2) effect of benzene and furan ring at N-position; (3) effect of aliphatic and aromatic hydroxy groups; (4) effect of triple bond group at N-position; (5) effect of N-acyl group and ketone group; (6) effect of methylenedioxy and methoxy groups on benzene ring; and (7) comparison between phenyltertiarybutylamines and phenylisopropylamines. After shaving the back hair and i.p. administration of drugs to Dark-Agouti rats (5 mg/kg, 10 days, n = 3), the areas under the concentration versus time curve (AUCs) of drugs in the plasma and the concentrations in hair newly grown for 4 weeks were determined by gas chromatography-mass spectrometry. The ICRs represented by the ratios of hair concentrations to AUCs were compared with those of amphetamine (AP) and methamphetamine (MA). The ICRs of N-alkyl AP increased depending on the length of carbon branches from proton to propyl (C3 > C2 > C1 > H) at N-position. The compounds containing a benzene or furan ring at the N-position (benzphetamine, clobenzorex, norbenzphetamine, prenylamine, furfenorex, and norfurfenorex) had much higher ICRs than those of AP or MA, suggesting that a benzene or furan ring increases their ICRs. The ICRs of deprenyl, nordeprenyl, and fenproporex were significantly low, implying that triple bonds such as of a propargyl or cyano group serve as a negative factor for the ICRs. An ephedrine group (ephedrine, methylephedrine, phenylpropanolamine) showed slightly lower ICRs than the corresponding amphetamine group. However, a hydroxy group on benzene ring apparently decreased the ICRs. Methoxy and methylenedioxy groups on benzene ring distinctly increased their ICRs. The lack of basicity such as N-formyl MA, N-acetyl AP, and N-acetyl MA dramatically lowered their ICRs to

  17. Rapid identification and quantification of methamphetamine and amphetamine in hair by gas chromatography/mass spectrometry coupled with micropulverized extraction, aqueous acetylation and microextraction by packed sorbent.

    Science.gov (United States)

    Miyaguchi, Hajime; Iwata, Yuko T; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Kuwayama, Kenji; Inoue, Hiroyuki

    2009-05-01

    We developed a rapid identification and quantification method for the toxicological analysis of methamphetamine and amphetamine in human hair by gas chromatography/mass spectrometry coupled with a novel combination of micropulverized extraction, aqueous acetylation and microextraction by packed sorbent (MEPS) named MiAMi-GC/MS. A washed hair sample (1-5 mg) was micropulverized for 5 min in a 2 mL plastic tube with 250 microL of water. An anion-exchange sorbent was added to adsorb anionic interferences. After removing the residue with a membrane-filter unit, sodium carbonate and acetic anhydride was admixed in turn. Acetylation was completed in approximately 20 min at room temperature. The acetylated analytes in the reaction liquid were concentrated to an octadecylsilica sorbent packed in the needle of a syringe by a CombiPAL autosampler. Elution was carried out with 50 microL of methanol, and the entire eluate injected into a gas chromatograph using a programmable temperature vaporizing (PTV) technique. The time required for sample preparation and GC/MS analysis was approximately 1 h from a washed hair sample, and an evaporation process was not required. Ranges for quantification were 0.20-50 (ng/mg) each for methamphetamine and amphetamine using 1 mg of hair. Accuracy and relative standard deviation (RSD) were evaluated intraday and interday at three concentrations, and the results were within the limit of a guidance issued by U.S. Food and Drug Administration. For identification, full-scan mass spectra of methamphetamine and amphetamine were obtained using 5 mg of fortified hair samples at 0.2 ng/mg. The extraction device of MEPS was durable for at least 300 extractions, whereas the liner of the gas chromatograph should be replaced after 20-30 times use. The carry over was estimated to be about 1-2%. This sample-preparation method coupled with GC/MS is fast and labor-saving in comparison with conventional methods.

  18. Adolescent Female Cannabinoid Exposure Diminishes the Reward-Facilitating Effects of Δ9-Tetrahydrocannabinol and d-Amphetamine in the Adult Male Offspring

    Directory of Open Access Journals (Sweden)

    George Panagis

    2017-04-01

    Full Text Available Marijuana is currently the most commonly abused illicit drug. According to recent studies, cannabinoid use occurring prior to pregnancy can impact brain plasticity and behavior in future generations. The purpose of the present study was to determine whether adolescent exposure of female rats to Δ9-tetrahydrocannabinol (Δ9-THC induces transgenerational effects on the reward-facilitating effects of Δ9-THC and d-amphetamine in their adult male offspring. Female Sprague-Dawley rats received Δ9-THC (0.1 or 1 mg/kg, i.p. or vehicle during postnatal days 28–50. As adults, females were mated with drug-naïve males. We then assessed potential alterations of the Δ9-THC’s (0, 0.1, 0.5, and 1 mg/kg, i.p. and d-amphetamine’s (0, 0.1, 0.5, and 1 mg/kg, i.p. reward-modifying effects using the curve-shift variant of the intracranial self-stimulation (ICSS procedure in their adult male F1 offspring. The reward-facilitating effect of the 0.1 mg dose of Δ9-THC was abolished in the F1 offspring of females that were exposed to Δ9-THC (0.1 or 1 mg/kg, whereas the reward-attenuating effect of the 1 mg dose of Δ9-THC remained unaltered. The reward-facilitating effects of 0.5 and 1 mg of d-amphetamine were significantly decreased in the F1 offspring of females that were exposed to Δ9-THC (1 mg/kg and 0.1 or 1 mg, respectively. The present results reveal that female Δ9-THC exposure during adolescence can diminish the reward-facilitating effects of Δ9-THC and d-amphetamine in the adult male offspring. These transgenerational effects occur in the absence of in utero exposure. It is speculated that Δ9-THC exposure during female adolescence may affect neural mechanisms that are shaping reward-related behavioral responses in a subsequent generation, as indicated by the shifts in the reward-facilitating effects of commonly used and abused drugs.

  19. Predictors of time to relapse in amphetamine-type substance users in the matrix treatment program in Iran: a Cox proportional hazard model application.

    Science.gov (United States)

    Moeeni, Maryam; Razaghi, Emran M; Ponnet, Koen; Torabi, Fatemeh; Shafiee, Seyed Ali; Pashaei, Tahereh

    2016-07-26

    The aim of this study was to determine which predictors influence the risk of relapse among a cohort of amphetamine-type substance (ATS) users in Iran. A Cox proportional hazards model was conducted to determine factors associated with the relapse time in the Matrix treatment program provided by the Iranian National Center of Addiction Studies (INCAS) between March 2010 and October 2011. Participating in more treatment sessions was associated with a lower probability of relapse. On the other hand, patients with less family support, longer dependence on ATS, and those with an experience of casual sex and a history of criminal offenses were more likely to relapse. This study broadens our understanding of factors influencing the risk of relapse in ATS use among an Iranian sample. The findings can guide practitioners during the treatment program.

  20. Synthesis of polystyrene, poly(styrene/4-vinylpyridine), poly(p-nitrostyrene) and poly(p-aminostyrene)-coated silica and their extraction capabilities for amphetamine

    International Nuclear Information System (INIS)

    Sun Changmei; Zhang Shuanhong; Qu Rongjun; Sun Tao; Zhang Ying; Zhang Xiang; Song Jingyang

    2010-01-01

    Several novel organic-inorganic hybrid materials, including polystyrene-coated silica (SG-PS), poly(styrene/4-vinylpyridine)-coated silica (SG-PVP), poly(p-nitrostyrene)-coated silica (SG-PS-NO 2 ) and poly(p-aminostyrene)-coated silica (SG-PS-NH 2 ), were synthesized in order to improve the extraction methods of harmful stimulants via solid phase extraction. The materials were characterized using infrared spectra (IR), scanning electron microscope (SEM), Brunauer-Emmett-Teller (BET) surface area measurement and thermogravimetric analysis (TG). The application of the new materials in solid phase extraction columns to extract methamphetamine revealed that the extraction capability of poly(styrene/4-vinylpyridine)-coated silica is the best among the four materials, which provides novel supporter materials for extracting amphetamine-derived drugs.

  1. Synthesis of polystyrene, poly(styrene/4-vinylpyridine), poly(p-nitrostyrene) and poly(p-aminostyrene)-coated silica and their extraction capabilities for amphetamine

    Energy Technology Data Exchange (ETDEWEB)

    Sun Changmei; Zhang Shuanhong [School of Chemistry and Materials Science, Ludong University, Yantai, Shandong 264025 (China); Qu Rongjun, E-mail: qurongjun@eyou.com [School of Chemistry and Materials Science, Ludong University, Yantai, Shandong 264025 (China); Sun Tao; Zhang Ying; Zhang Xiang; Song Jingyang [School of Chemistry and Materials Science, Ludong University, Yantai, Shandong 264025 (China)

    2010-11-01

    Several novel organic-inorganic hybrid materials, including polystyrene-coated silica (SG-PS), poly(styrene/4-vinylpyridine)-coated silica (SG-PVP), poly(p-nitrostyrene)-coated silica (SG-PS-NO{sub 2}) and poly(p-aminostyrene)-coated silica (SG-PS-NH{sub 2}), were synthesized in order to improve the extraction methods of harmful stimulants via solid phase extraction. The materials were characterized using infrared spectra (IR), scanning electron microscope (SEM), Brunauer-Emmett-Teller (BET) surface area measurement and thermogravimetric analysis (TG). The application of the new materials in solid phase extraction columns to extract methamphetamine revealed that the extraction capability of poly(styrene/4-vinylpyridine)-coated silica is the best among the four materials, which provides novel supporter materials for extracting amphetamine-derived drugs.

  2. Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

    DEFF Research Database (Denmark)

    Palner, Mikael; Kjaerby, Celia; Knudsen, Gitte M

    2011-01-01

    It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved...... to be more vulnerable to competition from endogenous dopamine than was the antagonist ligand [(11)C]raclopride, measured ex vivo in mouse striatum, and subsequently in multi-tracer PET studies of analogous design. Based on these results, we predicted that prolonged dopamine depletion would result...... in a preferential increase in agonist binding, and a lesser competition from residual dopamine to the agonist binding. To test this hypothesis we used autoradiography to measure [(3)H]NPA and [(3)H]raclopride binding sites in hemi-parkinsonian rats with unilateral 6-OHDA lesions, with and without amphetamine...

  3. Cocaine- and amphetamine-regulated transcript is present in hypothalamic neuroendocrine neurones and is released to the hypothalamic-pituitary portal circuit

    DEFF Research Database (Denmark)

    Larsen, P J; Seier, V; Fink-Jensen, A

    2003-01-01

    Cocaine- and amphetamine-regulated transcript (CART) is present in a number of hypothalamic nuclei. Besides actions in circuits regulating feeding behaviour and stress responses, the hypothalamic functions of CART are largely unknown. We report that CART immunoreactivity is present in hypothalami......, supraoptic, paraventricular (PVN) and periventricular nuclei of the hypothalamus. In the PVN, CART-positive neuroendocrine neurones were found in all of cytoarchitectonically identified nuclei. In the periventricular nucleus, approximately one-third of somatostatin cells were also CART......-immunoreactive. In the medial parvicellular subnucleus of the PVN, CART and FG coexisted with thyrotrophin-releasing hormone, whereas very few of the corticotrophin-releasing hormone containing cells were CART-immunoreactive. In the arcuate nucleus, CART was extensively colocalized with pro...

  4. Designation of Alpha-Phenylacetoacetonitrile (APAAN), a Precursor Chemical Used in the Illicit Manufacture of Phenylacetone, Methamphetamine, and Amphetamine, as a List I Chemical. Final rule.

    Science.gov (United States)

    2017-07-14

    The Drug Enforcement Administration (DEA) is finalizing the designation of the chemical alpha-phenylacetoacetonitrile (APAAN) and its salts, optical isomers, and salts of optical isomers, as a list I chemical under the Controlled Substances Act (CSA). The DEA proposed control of APAAN, due to its use in clandestine laboratories to illicitly manufacture the schedule II controlled substances phenylacetone (also known as phenyl-2-propanone or P2P), methamphetamine, and amphetamine. This rulemaking finalizes, without change, the control of APAAN as a list I chemical. This action does not establish a threshold for domestic and international transactions of APAAN. As such, all transactions involving APAAN, regardless of size, shall be regulated. In addition, chemical mixtures containing APAAN are not exempt from regulatory requirements at any concentration. Therefore, all transactions of chemical mixtures containing any quantity of APAAN shall be regulated pursuant to the CSA. However, manufacturers may submit an application for exemption for those mixtures that do not qualify for automatic exemption.

  5. Monolithic silica spin column extraction and simultaneous derivatization of amphetamines and 3,4-methylenedioxyamphetamines in human urine for gas chromatographic-mass spectrometric detection

    Energy Technology Data Exchange (ETDEWEB)

    Nakamoto, Akihiro [Scientific Investigation Laboratory, Hiroshima Prefectural Police Headquarters, Kohnan 2-26-3, Naka-ku, Hiroshima 730-0825 (Japan); Nishida, Manami [Hiroshima University Technical Center, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan); Saito, Takeshi [Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa 259-1143 (Japan); Kishiyama, Izumi; Miyazaki, Shota [GL Sciences Inc., Sayamagahara 237-2, Iruma, Saitama 358-0032 (Japan); Murakami, Katsunori [Scientific Investigation Laboratory, Hiroshima Prefectural Police Headquarters, Kohnan 2-26-3, Naka-ku, Hiroshima 730-0825 (Japan); Nagao, Masataka [Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan); Namura, Akira, E-mail: namera@hiroshima-u.ac.jp [Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan)

    2010-02-19

    A simple, sensitive, and specific method with gas chromatography-mass spectrometry was developed for simultaneous extraction and derivatization of amphetamines (APs) and 3,4-methylenedioxyamphetamines (MDAs) in human urine by using a monolithic silica spin column. All the procedures, such as sample loading, washing, and elution were performed by centrifugation. APs and MDAs in urine were adsorbed on the monolithic silica and derivatized with propyl chloroformate in the column. Methamphetamine-d{sub 5} was used as an internal standard. The linear ranges were 0.01-5.0 {mu}g mL{sup -1} for methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) and 0.02-5.0 {mu}g mL{sup -1} for amphetamine (AP) and 3,4-methylenedioxyamphetamine (MDA) (coefficient of correlation {>=}0.995). The recovery of APs and MDAs in urine was 84-94%, and the relative standard deviation of the intra- and interday reproducibility for urine samples containing 0.1, 1.0, and 4.0 {mu}g mL{sup -1} of APs and MDAs ranged from 1.4% to 13.6%. The lowest detection limit (signal-to-noise ratio {>=} 3) in urine was 5 ng mL{sup -1} for MA and MDMA and 10 ng mL{sup -1} for AP and MDA. The proposed method can be used to perform simultaneous extraction and derivatization on spin columns that have been loaded with a small quantity of solvent by using centrifugation.

  6. Enhanced visual responses in the superior colliculus in an animal model of attention-deficit hyperactivity disorder and their suppression by D-amphetamine.

    Science.gov (United States)

    Clements, K M; Devonshire, I M; Reynolds, J N J; Overton, P G

    2014-08-22

    Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by overactivity, impulsiveness and attentional problems, including an increase in distractibility. A structure that is intimately linked with distractibility is the superior colliculus (SC), a midbrain sensory structure which plays a particular role in the production of eye and head movements. Although others have proposed the involvement of such diverse elements as the frontal cortex and forebrain noradrenaline in ADHD, given the role of the colliculus in distractibility and the increased distractibility in ADHD, we have proposed that distractibility in ADHD arises due to collicular sensory hyper-responsiveness. To further investigate this possibility, we recorded the extracellular activity (multi-unit (MUA) and local field potential (LFP)) in the superficial visual layers of the SC in an animal model of ADHD, the New Zealand genetically hypertensive (GH) rat, in response to wholefield light flashes. The MUA and LFP peak amplitude and summed activity within a one-second time window post-stimulus were both significantly greater in GH rats than in Wistar controls, across the full range of stimulus intensities. Given that baseline firing rate did not differ between the strains, this suggests that the signal-to-noise ratio is elevated in GH animals. D-Amphetamine reduced the peak amplitude and summed activity of the multi-unit response in Wistar animals. It also reduced the peak amplitude and summed activity of the multi-unit response in GH animals, at higher doses bringing it down to levels that were equivalent to those of Wistar animals at baseline. The present results provide convergent evidence that a collicular dysfunction (sensory hyper-responsiveness) is present in ADHD, and that it may underlie the enhanced distractibility. In addition, D-amphetamine - a widely used treatment in ADHD - may have one of its loci of therapeutic action at the level of the

  7. Chronic atomoxetine treatment during adolescence does not influence decision-making on a rodent gambling task, but does modulate amphetamine's effect on impulsive action in adulthood.

    Science.gov (United States)

    Silveira, Mason M; Murch, W Spencer; Clark, Luke; Winstanley, Catharine A

    2016-06-01

    In addition to the symptoms of inattention, hyperactivity, and impulsivity, individuals with attention deficit hyperactivity disorder exhibit impaired performance on tests of real-world cost/benefit decision-making. Atomoxetine, a nonstimulant drug approved for the treatment of attention deficit hyperactivity disorder, is a selective norepinephrine reuptake inhibitor administered chronically during adolescence, a time during which the frontal brain regions necessary for executive function undergo extensive maturation. This treatment protocol can affect behavior well into adulthood, but whether it produces long-term changes in complex decision-making has not been investigated. Twenty-four Long-Evans rats were administered saline or 1.0 mg/kg atomoxetine daily from postnatal day 40 to 54. Two weeks after treatment, the adult rats were trained and assessed on the rodent gambling task, in which the animals chose from four options varying in reward, punishment, and uncertainty. Impulsive action was also measured by recording the number of premature responses made. Regardless of the treatment administered during adolescence, rats learned to favor the advantageous options characterized by small, low-penalty rewards in lieu of the larger, higher-penalty reward options. Rodent gambling task performance was then assessed following acute treatment with atomoxetine (0.1-1.0 mg/kg) and amphetamine (0.3-1.5 mg/kg). Across groups, the highest dose of atomoxetine impaired decision-making and decreased premature responding at all doses tested. Amphetamine also impaired choice performance, but selectively increased impulsive action in rats that had previously received atomoxetine treatment during adolescence. These findings contribute to our understanding of the long-term effects associated with chronic adolescent atomoxetine exposure and suggest that this treatment does not alter decision-making under conditions of risk and uncertainty in adulthood.

  8. A novel screening method for 64 new psychoactive substances and 5 amphetamines in blood by LC-MS/MS and application to real cases.

    Science.gov (United States)

    Vaiano, Fabio; Busardò, Francesco P; Palumbo, Diego; Kyriakou, Chrystalla; Fioravanti, Alessia; Catalani, Valeria; Mari, Francesco; Bertol, Elisabetta

    2016-09-10

    Identification and quantification of new psychoactive substances (NPS), both in biological and non-biological samples, represent a hard challenge for forensic toxicologists. NPS are increasingly emerging on illegal drug market. Many cases of co-consumption of NPS and other substances have also been reported. Hence, the development of analytical methods aiming at the detection of a broad-spectrum of compounds (NPS and "traditional" drugs) could be helpful. In this paper, a fully validated screening method in blood for the simultaneous detection of 69 substances, including 64 NPS (28 synthetic cannabinoids, 19 synthetic cathinones, 5 phenethylamines, 3 indanes, 2 piperazines, 2 tryptamines, 2 phencyclidine, methoxetamine, ketamine and its metabolite) and 5 amphetamines (amphetamine, methamphetamine, MDMA, MDA, 3,4-methylenedioxy-N-ethylamphetamine - MDEA-) by a dynamic multiple reaction monitoring analysis through liquid chromatography - tandem mass spectrometry (LC-MS/MS) is described. This method is very fast, easy to perform and cheap as it only requires the deproteinization of 200μL of blood sample with acetonitrile. The chromatographic separation is achieved with a C18 column. The analysis is very sensitive, with limits of quantification ranging from 0.1 to 0.5ng/mL. The method is linear from 1 to 100ng/mL and the coefficient of determination (R(2)) was always above 0.9900. Precision and accuracy were acceptable at any quality control level and recovery efficiency range was 72-110%. Matrix effects did not negatively affect the analytical sensitivity. This method was successfully applied to three real cases, allowing identification and quantification of: mephedrone and methamphetamine (post-mortem); ketamine, MDMA and MDA (post-mortem); AB-FUBINACA (ante-mortem). Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Monolithic silica spin column extraction and simultaneous derivatization of amphetamines and 3,4-methylenedioxyamphetamines in human urine for gas chromatographic-mass spectrometric detection.

    Science.gov (United States)

    Nakamoto, Akihiro; Nishida, Manami; Saito, Takeshi; Kishiyama, Izumi; Miyazaki, Shota; Murakami, Katsunori; Nagao, Masataka; Namura, Akira

    2010-02-19

    A simple, sensitive, and specific method with gas chromatography-mass spectrometry was developed for simultaneous extraction and derivatization of amphetamines (APs) and 3,4-methylenedioxyamphetamines (MDAs) in human urine by using a monolithic silica spin column. All the procedures, such as sample loading, washing, and elution were performed by centrifugation. APs and MDAs in urine were adsorbed on the monolithic silica and derivatized with propyl chloroformate in the column. Methamphetamine-d(5) was used as an internal standard. The linear ranges were 0.01-5.0 microg mL(-1) for methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) and 0.02-5.0 microg mL(-1) for amphetamine (AP) and 3,4-methylenedioxyamphetamine (MDA) (coefficient of correlation > or = 0.995). The recovery of APs and MDAs in urine was 84-94%, and the relative standard deviation of the intra- and interday reproducibility for urine samples containing 0.1, 1.0, and 4.0 microg mL(-1) of APs and MDAs ranged from 1.4% to 13.6%. The lowest detection limit (signal-to-noise ratio > or = 3) in urine was 5 ng mL(-1) for MA and MDMA and 10 ng mL(-1) for AP and MDA. The proposed method can be used to perform simultaneous extraction and derivatization on spin columns that have been loaded with a small quantity of solvent by using centrifugation. Copyright 2009 Elsevier B.V. All rights reserved.

  10. Characterisation of aqueous waste produced during the clandestine production of amphetamine following the Leuckart route utilising solid-phase extraction gas chromatography-mass spectrometry and capillary electrophoresis with contactless conductivity detection.

    Science.gov (United States)

    Hauser, Frank M; Hulshof, Janneke W; Rößler, Thorsten; Zimmermann, Ralf; Pütz, Michael

    2018-04-18

    Chemical waste from the clandestine production of amphetamine is of forensic and environmental importance due to its illegal nature which often leads to dumping into the environment. In this study, 27 aqueous amphetamine waste samples from controlled Leuckart reactions performed in Germany, the Netherlands, and Poland were characterised to increase knowledge about the chemical composition and physicochemical characteristics of such waste. Aqueous waste samples from different reaction steps were analysed to determine characteristic patterns which could be used for classification. Conductivity, pH, density, ionic load, and organic compounds were determined using different analytical methods. Conductivity values ranged from 1 to over 200 mS/cm, pH values from 0 to 14, and densities from 1.0 to 1.3 g/cm 3 . A capillary electrophoresis method with contactless conductivity detection (CE-C 4 D) was developed and validated to quantify chloride, sulphate, formate, ammonium, and sodium ions which were the most abundant ions in the investigated waste samples. A solid-phase extraction sample preparation was used prior to gas chromatography-mass spectrometry analysis to determine the organic compounds. Using the characterisation data of the known samples, it was possible to assign 16 seized clandestine waste samples from an amphetamine production to the corresponding synthesis step. The data also allowed us to draw conclusions about the synthesis procedure and used chemicals. The presented data and methods could support forensic investigations by showing the probative value of synthesis waste when investigating the illegal production of amphetamine. It can also act as starting point to develop new approaches to tackle the problem of clandestine waste dumping. Copyright © 2018 John Wiley & Sons, Ltd.

  11. 5-HT has contrasting effects in the frontal cortex, but not the hypothalamus, on changes in noradrenaline efflux induced by the monoamine releasing-agent, d-amphetamine, and the reuptake inhibitor, BTS 54 354.

    Science.gov (United States)

    Géranton, Sandrine M; Heal, David J; Stanford, S Clare

    2004-03-01

    There is extensive evidence for functional interactions between central noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used in freely-moving rats to compare the effects of 5-HT on noradrenergic transmission in the rat frontal cortex and hypothalamus. We studied the effects of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5-HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux of noradrenaline and on the noradrenergic responses to d-amphetamine, and the monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect spontaneous noradrenaline efflux in either brain region, whether or not alpha2-autoreceptors were inactivated by administration of the alpha2-antagonist, atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment augmented the amplitude of, and prolonged, the noradrenergic response to local infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50 microM). In the hypothalamus, pCPA did not affect the amplitude of the response to either of these agents but did prolong the effects of d-amphetamine on noradrenaline efflux. These findings suggest that serotonergic transmission has complex effects on the noradrenergic response to drugs that increase noradrenergic transmission in the frontal cortex, but has less influence in the hypothalamus.

  12. Uso de álcool e anfetaminas entre caminhoneiros de estrada Alcohol and amphetamines use among long-distance truck drivers

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    Eurípedes Costa do Nascimento

    2007-04-01

    Full Text Available O objetivo do estudo foi analisar a incidência do uso de álcool e anfetaminas entre caminhoneiros de estrada. Foram estudados 91 sujeitos, abordados em um posto de combustíveis em Passos, MG, em novembro de 2005. Os dados dos participantes foram obtidos por meio de um questionário contendo 19 questões de múltipla escolha. Utilizou-se para a análise dos dados estatística descritiva, teste do qui-quadrado e o coeficiente de correlação de Cramér. Os resultados indicaram que 66% dos caminhoneiros usavam anfetaminas durante os percursos de viagens, principalmente em postos de combustíveis (54% à beira das rodovias. O álcool era utilizado por 91% deles, dos quais 43% consumiam a bebida nos postos de combustíveis. Concluiu-se que há a necessidade de campanhas preventivas e informativas voltadas para esta categoria profissional nos postos de combustíveis e empresas de transportes, alertando sobre os riscos de ingestão dessas substâncias no período de trabalho.The purpose of the study was to assess the incidence of alcohol and amphetamine use among long-distance truck drivers. There were studied 91 truck drivers at the gas station in Passos, Southeastern Brazil, in November 2005. Data was collected using a questionnaire comprising 19 multiple choice questions. Descriptive statistics, Chi-square test and Cramér's correlation coefficient were used for data analysis. The results indicated that 66% of the long-distance truck drivers used amphetamines during their travels, mainly at gas stations along the highways (54%. Alcohol was consumed by 91% of them and 43% of them consumed it at gas stations. It is concluded that there is a need of preventive and education campaigns targeting this occupation category at gas stations and transportation companies, focusing on the risks of these substances use during working hours.

  13. A conveyor belt task for assessing visuo-motor coordination in the marmoset (Callithrix jacchus): effects of diazepam, chlorpromazine, pentobarbital and d-amphetamine.

    Science.gov (United States)

    D'Mello, G D; Duffy, E A; Miles, S S

    1985-01-01

    A conveyor belt task for assessing visuo-motor coordination in the marmoset is described. Animals are motivated by apple, a preferred food, under a state of minimal food deprivation. The apparatus used was designed to test animals within their home cages and not restrained in any way, thus avoiding possible confounding factors associated with restraint stress. Stable baseline levels of performance were reached by all animals in a median of 24 sessions. Performance was shown to be differentially sensitive to the effects of four psychoactive drugs. Moderate doses of diazepam, chlorpromazine and pentobarbital disrupted visuo-motor coordination in a dose-related manner. The possibility that disruption of performance observed at higher doses may have resulted from non-specific actions of these drugs such as decreases in feeding motivation were not supported by results from ancillary experiments. Changes in performance characteristic of high dose effects were similar in nature to changes observed when the degree of task difficulty was increased. Doses of d-amphetamine up to and including those reported to produce signs of stereotypy failed to influence performance. The potential of the conveyor belt task for measuring visuo-motor coordination in both primate and rodent species is discussed.

  14. Immunohistochemical localization of cocaine- and amphetamine-regulated transcript peptide (CARTp) in the brain of the pigeon (Columba livia) and zebra finch (Taeniopygia guttata).

    Science.gov (United States)

    Gutierrez-Ibanez, Cristian; Iwaniuk, Andrew N; Jensen, Megan; Graham, David J; Pogány, Ákos; Mongomery, Benjamin C; Stafford, James L; Luksch, Harald; Wylie, Douglas R

    2016-12-15

    Cocaine- and amphetamine-regulated transcript peptides (CARTp) are neuropeptides that act as neurotransmitters in the brain of vertebrates. The expression of CARTp has been characterized in teleosts, amphibians, and several mammalian species, but comparative data in reptiles and birds are nonexistent. In this study, we show the distribution of immunoreactivity against CART peptides (CARTp-ir) in the brains of two bird species: the pigeon (Columba livia) and zebra finch (Taeniopygia guttata). We found CARTp-ir cells and terminals in the brains of both, but no major differences between the two species. As in mammals, teleost fish, and amphibians, CARTp-ir terminals and cells were abundant in subpallial regions, particularly the striatum and nucleus accumbens. We also found CARTp-ir cells and terminals in the hypothalamus, and a large number of CARTp-ir terminals in the substantia nigra, ventral tegmental area, periaqueductal gray, parabrachial nucleus, and dorsal vagal complex. However, in contrast to other vertebrates, CARTp-ir was not found in the olfactory bulb. In addition there was almost no CARTp-ir in the pallium or the hippocampal formation, and little CARTp-ir in the cerebellum. The conserved expression of CARTp in the subpallium, hypothalamus, and dorsal vagal complex of birds suggests that some of the functions of CARTp, such as regulation of food intake and interactions with the social control network and mesolimbic reward system, are conserved among vertebrates. J. Comp. Neurol. 524:3747-3773, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Rebound effects with long-acting amphetamine or methylphenidate stimulant medication preparations among adolescent male drivers with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Cox, Daniel J; Moore, Melissa; Burket, Roger; Merkel, R Lawrence; Mikami, Amori Yee; Kovatchev, Boris

    2008-02-01

    This study investigated whether OROS methylphenidate (OROS MPH, Concerta) or extended-release mixed amphetamine salts (se-AMPH ER, Adderall XR) were associated with worsening of driving performance, or drug rebound, relative to placebo 16-17 hours post-ingestion. Nineteen male adolescent drivers aged 17-19 with attention-deficit/hyperactivity disorder (ADHD) were compared on a virtual reality driving simulator and an on-road drive after taking 72 mg of OROS MPH, 30 mg of se-AMPH ER, or placebo. Medication was taken at 08:00 in a randomized, double-blind, placebo-controlled, crossover study. Participants drove a simulator at 17:00, 20:00, 23:00, and 01:00, and drove their own cars over a 16-mile road course at 24:00. The main outcome measures were composite scores of driving performance. Neither OROS MPH nor se-AMPH ER was associated with significant worsening of simulator performance relative to placebo 17 hours post-ingestion in group comparisons. However, inattentive on-road driving errors were significantly more common on se-AMPH ER relative to placebo at midnight (p = 0.04), suggesting possible rebound. During both late simulator and on-road testing, driving performance variance was approximately 300% greater during the se-AMPH ER compared to the OROS MPH condition.

  16. Association of the Cocaine- and Amphetamine-Regulated Transcript Prepropeptide Gene (CARTPT) rs2239670 Variant with Obesity among Kampar Health Clinic Patrons, Malaysia.

    Science.gov (United States)

    Lisa, Yeo; Sook-, Ha Fan; Yee-, How Say

    2012-01-01

    Cocaine- and amphetamine-regulated transcript (CART) is a hypothalamic anorectic neuropeptide that controls feeding behaviour and body weight. The study objective was to investigate the association of the CART prepropeptide gene (CARTPT) rs2239670 variant with obesity and its related anthropometric indicators among patients of a Malaysian health clinic in Kampar, Perak, Malaysia. A total of 300 Malay/Peninsular Bumiputera, Chinese, and Indian subjects (115 males, 185 females; 163 non-obese, 137 obese) were recruited by convenience sampling, and anthropometric measurements, blood pressures, and pulse rate were taken. Genotyping was performed using AvaII polymerase chain reaction-restriction fragment length polymorphism. Genotyping revealed 203 (67.7%), 90 (30.0%), and 7 (2.3%) subjects with the GG, GA, and AA genotypes, respectively, with a minor allele (A) frequency of 0.17. No significant difference in the CARTPT rs2239670 genotype and allele distribution was found between obese and non-obese subjects, and logistic regression showed no association between the mutated genotypes (GA, AA) and allele (A) with obesity, even after adjusting for age, gender, and ethnicity. Furthermore, the measurements did not differ significantly between the genotypes and alleles. No significant difference in the genotype and allele distribution was found among genders, but they were significantly different among ethnicities (P = 0.030 and P = 0.019, respectively). CARTPT rs2239670 is not a predictor for obesity among the Malaysian subjects in this study.

  17. Repeated administration of D-amphetamine induces loss of [{sup 123}I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    Energy Technology Data Exchange (ETDEWEB)

    Booij, Jan [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands)]. E-mail: j.booij@amc.uva.nl; Bruin, Kora de [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands); Gunning, W. Boudewijn [Department of Neurology, Epilepsy Centre Kempenhaeghe, 5590 AB Heeze (Netherlands)

    2006-04-15

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([{sup 123}I]FP-CIT). Methods: Groups of male rats (n=10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [{sup 123}I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. Results: In D-AMPH but not METH-treated rats, striatal [{sup 123}I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. Conclusion: These data show that [{sup 123}I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo.

  18. Repeated administration of D-amphetamine induces loss of [123I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    International Nuclear Information System (INIS)

    Booij, Jan; Bruin, Kora de; Gunning, W. Boudewijn

    2006-01-01

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([ 123 I]FP-CIT). Methods: Groups of male rats (n=10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [ 123 I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. Results: In D-AMPH but not METH-treated rats, striatal [ 123 I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. Conclusion: These data show that [ 123 I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo

  19. A first-principles study on the adsorption behavior of amphetamine on pristine, P- and Al-doped B12N12 nano-cages

    Science.gov (United States)

    Bahrami, Aidin; Seidi, Shahram; Baheri, Tahmineh; Aghamohammadi, Mohammad

    2013-12-01

    The first-principles computations using density functional theory (DFT) calculations at the M062X/6-311++G** level have been applied to scrutinize the adsorption behavior of amphetamine (AMP) molecule on the external surface of pristine, P- and Al-doped B12N12 nano-cages. In order to gain insight into the binding features of pristine and doped B12N12 complexes as adsorbent with AMP, the structural and electronic parameters as well as the Atoms in Molecules (AIM) properties were examined. The results showed that AMP prefers to adsorb via its nitrogen atom on the Lewis acid sites of B and Al atoms of the nano-cages. On the basis of calculated density of states, the interaction of AMP with the external wall of B12N12 leads to the remarkable differences in their conductivities. Presence of polar solvent increases the AMP adsorption on the nano-cage. In addition, AIM based analyses indicated an electrostatic nature for N-B interaction in Amph-B12N12 and partial covalent for N-Al in AMP-B11AlN12. Based on calculated results, the B12N12 and B11AlN12 nano-cages are expected to be a potential efficient adsorbent as well as sensors for adsorption of AMP in environmental systems.

  20. Association of the Cocaine- and Amphetamine-Regulated Transcript Prepropeptide Gene (CARTPT) rs2239670 Variant with Obesity among Kampar Health Clinic Patrons, Malaysia

    Science.gov (United States)

    Lisa, Yeo; Sook-, Ha Fan; Yee-, How Say

    2012-01-01

    Background: Cocaine- and amphetamine-regulated transcript (CART) is a hypothalamic anorectic neuropeptide that controls feeding behaviour and body weight. The study objective was to investigate the association of the CART prepropeptide gene (CARTPT) rs2239670 variant with obesity and its related anthropometric indicators among patients of a Malaysian health clinic in Kampar, Perak, Malaysia. Methods: A total of 300 Malay/Peninsular Bumiputera, Chinese, and Indian subjects (115 males, 185 females; 163 non-obese, 137 obese) were recruited by convenience sampling, and anthropometric measurements, blood pressures, and pulse rate were taken. Genotyping was performed using AvaII polymerase chain reaction–restriction fragment length polymorphism. Results: Genotyping revealed 203 (67.7%), 90 (30.0%), and 7 (2.3%) subjects with the GG, GA, and AA genotypes, respectively, with a minor allele (A) frequency of 0.17. No significant difference in the CARTPT rs2239670 genotype and allele distribution was found between obese and non-obese subjects, and logistic regression showed no association between the mutated genotypes (GA, AA) and allele (A) with obesity, even after adjusting for age, gender, and ethnicity. Furthermore, the measurements did not differ significantly between the genotypes and alleles. No significant difference in the genotype and allele distribution was found among genders, but they were significantly different among ethnicities (P = 0.030 and P = 0.019, respectively). Conclusion: CARTPT rs2239670 is not a predictor for obesity among the Malaysian subjects in this study. PMID:22977374

  1. Cocaine- and amphetamine-regulated transcript facilitates the neurite outgrowth in cortical neurons after oxygen and glucose deprivation through PTN-dependent pathway.

    Science.gov (United States)

    Wang, Y; Qiu, B; Liu, J; Zhu, Wei-Guo; Zhu, S

    2014-09-26

    Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide that plays neuroprotective roles in cerebral ischemia and reperfusion (I/R) injury in animal models or oxygen and glucose deprivation (OGD) in cultured neurons. Recent data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain. However, little is known about the effects of post-treatment with CART during the neuronal recovery after OGD and reoxygenation in cultured primary cortical neurons. The present study was to investigate the role of CART treated after OGD injury in neurons. Primary mouse cortical neurons were subjected to OGD and then treated with CART. Our data show that post-treatment with CART reduced the neuronal apoptosis caused by OGD injury. In addition, CART repaired OGD-impaired cortical neurons by increasing the expression of growth-associated protein 43 (GAP43), which promotes neurite outgrowth. This effect depends on pleiotrophin (PTN) as siRNA-mediated PTN knockdown totally abolished the increase in CART-stimulated GAP43 protein levels. In summary, our findings demonstrate that CART repairs the neuronal injury after OGD by facilitating neurite outgrowth through PTN-dependent pathway. The role for CART in neurite outgrowth makes it a new potential therapeutic agent for the treatment of neurodegenerative diseases. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Cocaine- and amphetamine-regulated transcript peptide increases mitochondrial respiratory chain complex II activity and protects against oxygen-glucose deprivation in neurons.

    Science.gov (United States)

    Sha, Dujuan; Wang, Luna; Zhang, Jun; Qian, Lai; Li, Qiming; Li, Jin; Qian, Jian; Gu, Shuangshuang; Han, Ling; Xu, Peng; Xu, Yun

    2014-09-25

    The mechanisms of ischemic stroke, a main cause of disability and death, are complicated. Ischemic stroke results from the interaction of various factors including oxidative stress, a key pathological mechanism that plays an important role during the acute stage of ischemic brain injury. This study demonstrated that cocaine- and amphetamine-regulated transcript (CART) peptide, specifically CART55-102, increased the survival rate, but decreased the mortality of neurons exposed to oxygen-glucose deprivation (OGD), in a dose-dependent manner. The above-mentioned effects of CART55-102 were most significant at 0.4nM. These results indicated that CART55-102 suppressed neurotoxicity and enhanced neuronal survival after oxygen-glucose deprivation. CART55-102 (0.4nM) significantly diminished reactive oxygen species levels and markedly increased the activity of mitochondrial respiratory chain complex II in oxygen-glucose deprived neurons. In summary, CART55-102 suppressed oxidative stress in oxygen-glucose deprived neurons, possibly through elevating the activity of mitochondrial respiratory chain complex II. This result provides evidence for the development of CART55-102 as an antioxidant drug. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Cocaine- and amphetamine-regulated transcript is present in hypothalamic neuroendocrine neurones and is released to the hypothalamic-pituitary portal circuit.

    Science.gov (United States)

    Larsen, P J; Seier, V; Fink-Jensen, A; Holst, J J; Warberg, J; Vrang, N

    2003-03-01

    Cocaine- and amphetamine-regulated transcript (CART) is present in a number of hypothalamic nuclei. Besides actions in circuits regulating feeding behaviour and stress responses, the hypothalamic functions of CART are largely unknown. We report that CART immunoreactivity is present in hypothalamic neuroendocrine neurones. Adult male rats received a systemic injection of the neuronal tracer Fluorogold (FG) 2 days before fixation, and subsequent double- and triple-labelling immunoflourescence analysis demonstrated that neuroendocrine CART-containing neurones were present in the anteroventral periventricular, supraoptic, paraventricular (PVN) and periventricular nuclei of the hypothalamus. In the PVN, CART-positive neuroendocrine neurones were found in all of cytoarchitectonically identified nuclei. In the periventricular nucleus, approximately one-third of somatostatin cells were also CART-immunoreactive. In the medial parvicellular subnucleus of the PVN, CART and FG coexisted with thyrotrophin-releasing hormone, whereas very few of the corticotrophin-releasing hormone containing cells were CART-immunoreactive. In the arcuate nucleus, CART was extensively colocalized with pro-opiomelanocortin in the ventrolateral part, but completely absent from neuroendocrine neurones of the dorsomedial part. To assess the possible role of CART as a hypothalamic-releasing factor, immunoreactive CART was measured in blood samples from the long portal vessels connecting the median eminence with the anterior pituitary gland. Adult male rats were anaesthetized and the infundibular stalk exposed via a transpharyngeal approach. The long portal vessels were transected and blood collected in 30-min periods (one prestimulatory and three poststimulatory periods). Compared to systemic venous plasma samples, baseline concentrations of immunoreactive CART were elevated in portal plasma. Exposure to sodium nitroprusside hypotension triggered a two-fold elevation of portal CART42

  4. The role of the polymorphic efflux transporter P-glycoprotein on the brain accumulation of d-methylphenidate and d-amphetamine.

    Science.gov (United States)

    Zhu, Hao-Jie; Wang, Jun-Sheng; DeVane, C Lindsay; Williard, Robin L; Donovan, Jennifer L; Middaugh, Lawrence D; Gibson, Brian B; Patrick, Kennerly S; Markowitz, John S

    2006-07-01

    The psychostimulant medications methylphenidate (MPH) and amphetamine (AMP), available in various ratios or enantiopure formulations of their respective active dextrorotary isomers, constitute the majority of agents used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Substantial interindividual variability occurs in their pharmacokinetics and tolerability. Little is known regarding the potential role of drug transporters such as P-glycoprotein (P-gp) in psychostimulant pharmacokinetics and response. Therefore, experiments were carried out in P-gp knockout (KO) mice versus wild-type (WT) mice after intraperitoneal dosing (2.5 mg/kg) of d-MPH or (3.0 mg/kg) of d-AMP. After the administration of each psychostimulant, locomotor activity was assessed at 30-min intervals for 2 h. Total brain-to-plasma drug concentration ratios were determined at 10-, 30-, and 80-min postdosing time-points. The results showed no statistically supported genotypic difference in d-AMP-induced locomotor activity stimulation or in brain-to-plasma ratio of d-AMP. As for d-MPH, the P-gp KO mice had 33% higher brain concentrations (p brain-to-plasma ratios (p brain concentrations, d-MPH-induced locomotor activity increase was attenuated for P-gp compared with that for WT mice. These data indicate that P-gp has no apparent effect on the pharmacokinetics and pharmacodynamics of d-AMP. In addition, d-MPH is a relatively weak P-gp substrate, and its entry into the brain may be limited by P-gp. Furthermore, the mechanism by which d-MPH-induced locomotor activity was attenuated in P-gp KO mice remains to be elucidated.

  5. Mixed-amphetamine salts increase abstinence from marijuana in patients with co-occurring attention-deficit/hyperactivity disorder and cocaine dependence.

    Science.gov (United States)

    Notzon, Daniel P; Mariani, John J; Pavlicova, Martina; Glass, Andrew; Mahony, Amy L; Brooks, Daniel J; Grabowski, John; Levin, Frances R

    2016-12-01

    The prevalence of ADHD is greater in substance use disorders than the general population, and ADHD and substance use disorders share neurobiological features such as dysregulation of reward circuitry. We tested the hypothesis that stimulants would decrease marijuana use in a randomized controlled trial of extended release mixed amphetamine salts (MAS-XR) for treatment of co-occurring ADHD and cocaine use disorders. Marijuana users were defined as participants reporting use in the 30 days before study initiation, collected with timeline follow-back. The original 14-week trial utilized a 3-arm randomized design, comparing placebo, MAS-XR 60 mg, and MAS-XR 80 mg. For this analysis, both MAS-XR groups were combined, leaving n = 20 in the placebo group and n = 37 in the MAS-XR group. The primary outcome was proportion of subjects reporting any marijuana use per study week. Comparisons between groups were made using a logistic mixed effects model incorporating multiple predictors and modeling time-by-treatment interactions. There were no significant baseline differences in marijuana use frequency and quantity. There was a significant decrease in the proportion of participants using marijuana over time in the MAS-XR group, but no difference in the proportion of marijuana-use days over time. Treatment of ADHD and comorbid cocaine use disorders with MAS-XR is associated with increased weekly abstinence from marijuana but not with a decrease in the proportion of marijuana using days per week. Stimulant treatment of ADHD and cocaine use disorders may diminish co-occurring cannabis use. (Am J Addict 2016;25:666-672). © 2016 American Academy of Addiction Psychiatry.

  6. Effect of desipramine and citalopram treatment on forced swimming test-induced changes in cocaine- and amphetamine-regulated transcript (CART) immunoreactivity in mice.

    Science.gov (United States)

    Chung, Sung; Kim, Hee Jeong; Kim, Hyun Ju; Choi, Sun Hye; Kim, Jin Wook; Kim, Jeong Min; Shin, Kyung Ho

    2014-05-01

    Recent study demonstrates antidepressant-like effect of cocaine- and amphetamine-regulated transcript (CART) in the forced swimming test (FST), but less is known about whether antidepressant treatments alter levels of CART immunoreactivity (CART-IR) in the FST. To explore this possibility, we assessed the treatment effects of desipramine and citalopram, which inhibit the reuptake of norepinephrine and serotonin into the presynaptic terminals, respectively, on changes in levels of CART-IR before and after the test swim in mouse brain. Levels of CART-IR in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), and hypothalamic paraventricular nucleus (PVN) were significantly increased before the test swim by desipramine and citalopram treatments. This increase in CART-IR in the AcbSh, dBNST, and PVN before the test swim remained elevated by desipramine treatment after the test swim, but this increase in these brain areas returned to near control levels after test swim by citalopram treatment. Citalopram, but not desipramine, treatment increased levels of CART-IR in the central nucleus of the amygdala (CeA) and the locus ceruleus (LC) before the test swim, and this increase was returned to control levels after the test swim in the CeA, but not in the LC. These results suggest common and distinct regulation of CART by desipramine and citalopram treatments in the FST and raise the possibility that CART in the AcbSh, dBNST, and CeA may be involved in antidepressant-like effect in the FST.

  7. Dynamics of cocaine- and amphetamine-regulated transcript containing cell changes in the adrenal glands of two kidney, one clip rats.

    Science.gov (United States)

    Kasacka, Irena; Piotrowska, Zaneta; Janiuk, Izabela; Zbucki, Robert

    2014-10-01

    Taking into consideration the homeostatic disorders resulting from renal hypertension and the essential role of cocaine- and amphetamine-regulated transcript (CART) in maintaining homeostasis by regulating many functions of the body, the question arises as to what extent the renovascular hypertension affects the morphology and dynamics of changes of CART-containing cells in the adrenal glands. The aim of the present study was to examine the distribution, morphology, and dynamics of changes of CART-containing cells in the adrenal glands of "two kidney, one clip" (2K1C) renovascular hypertension model in rats. The studies were carried out on the adrenal glands of rats after 3, 14, 28, 42, and 91 days from the renal artery clipping procedure. To identify neuroendocrine cells, immunohistochemical reaction was performed with the use of a specific antibody against CART. It was revealed that renovascular hypertension causes changes in the endocrine cells containing CART in the adrenal glands of rats. The changes observed in the endocrine cells depend on the time when the rats with experimentally induced hypertension were examined. In the first period of hypertension, the number and immunoreactivity of CART-containing cells were decreased, while from the 28-day test, it significantly increased, as compared to the control rats. CART is relevant to the regulation of homeostasis in the cardiovascular system and seems to be involved in renovascular hypertension. The results of the present work open the possibility of new therapeutic perspectives for the treatment of arterial hypertension, since CART function is involved in their pathophysiology. © 2014 by the Society for Experimental Biology and Medicine.

  8. Effects of gender on locomotor sensitivity to amphetamine, body weight, and fat mass in regulator of G protein signaling 9 (RGS9) knockout mice.

    Science.gov (United States)

    Walker, Paul D; Jarosz, Patricia A; Bouhamdan, Mohamad; MacKenzie, Robert G

    2015-01-01

    Regulator of G-protein signaling (RGS) protein 9-2 is enriched in the striatum where it modulates dopamine and opioid receptor-mediated signaling. RGS9 knockout (KO) mice show increased psychostimulant-induced behavioral sensitization, as well as exhibit higher body weights and greater fat accumulation compared to wild-type (WT) littermates. In the present study, we found gender influences on each of these phenotypic characteristics. Female RGS9 KO mice exhibited greater locomotor sensitization to amphetamine (1.0mg/kg) treatment as compared to male RGS9 KO mice. Male RGS9 KO mice showed increased body weights as compared to male WT littermates, while no such differences were detected in female mice. Quantitative magnetic resonance showed that male RGS9 KO mice accumulated greater fat mass vs. WT littermates at 5months of age. Such observations could not be explained by increased caloric consumption since male and female RGS9 KO mice demonstrated equivalent daily food intake as compared to their respective WT littermates. Although indirect calorimetry methods found decreased oxygen consumption and carbon dioxide production during the 12-hour dark phase in male RGS9 KO vs. WT mice which are indicative of less energy expenditure, male RGS9 KO mice exhibited lower levels of locomotor activity during this period. Genotype had no effect on metabolic activities when KO and WT groups were compared under fasting vs. feeding treatments. In summary, these results highlight the importance of factoring gender into the experimental design since many studies conducted in RGS9 KO mice utilize locomotor activity as a measured outcome. Copyright © 2014. Published by Elsevier Inc.

  9. Wipe sampling of amphetamine-type stimulants and recreational drugs on selected household surfaces with analysis by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry

    International Nuclear Information System (INIS)

    Madireddy, Sri Bharat; Bodeddula, Vanaja Reddy; Mansani, Sravan Kumar; Wells, Martha J.M.; Boles, Jeffrey O.

    2013-01-01

    Highlights: • Degree of sorption of eight drugs on eleven countertop surfaces was investigated. • Surface composition, volatility and solvent composition played a role in sorption. • Solvent-dependent migration was a key factor of consideration during remediation. • SPME-assisted volatility studies provided evidence for varying degrees of recovery. • Rapid three minute UPLC-QTOF method was developed to quantify the eight compounds. -- Abstract: Sorption characteristics of eight drugs related to recreational and clandestine activity—amphetamine, cocaine, heroin, N-formyl amphetamine, N-formyl methamphetamine, methamphetamine, 3, 4-methylenedioxymethamphetamine (MDMA), and pseudoephedrine—were evaluated on selected kitchen countertop surfaces. Methanol-dampened Whatman™ 40 filter paper wipes were used to collect samples from eleven surfaces including alkyd resin, ceramic tiles, glass, granite, laminate, limestone, marble, quartz compac, quartz real, soap stone, and stainless steel. The filter paper wipes were analyzed by a rapid three-minute UPLC-QTOF method, following ammonium acetate buffer (pH 5.8–6.2) extraction. The average percentage recoveries after 15 h of exposure to the surface materials tested, was found to be highest for cocaine and MDMA and lowest for amphetamine and methamphetamine. Among the eleven countertop surfaces, overall recoveries for marble were observed to be the least, whereas soapstone, quartz compac and stainless steel were among the highest. Scanning electron microscopic images of the surfaces provided a unique view of surface irregularities that potentially influenced drug recovery. Aging, migration, solvent composition, and volatility were examined. The variation in recovery of drugs was attributed to four key factors: compound volatility, surface composition, surface—compound interaction, and solvent composition

  10. Wipe sampling of amphetamine-type stimulants and recreational drugs on selected household surfaces with analysis by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Madireddy, Sri Bharat; Bodeddula, Vanaja Reddy; Mansani, Sravan Kumar; Wells, Martha J.M.; Boles, Jeffrey O., E-mail: jboles@tntech.edu

    2013-06-15

    Highlights: • Degree of sorption of eight drugs on eleven countertop surfaces was investigated. • Surface composition, volatility and solvent composition played a role in sorption. • Solvent-dependent migration was a key factor of consideration during remediation. • SPME-assisted volatility studies provided evidence for varying degrees of recovery. • Rapid three minute UPLC-QTOF method was developed to quantify the eight compounds. -- Abstract: Sorption characteristics of eight drugs related to recreational and clandestine activity—amphetamine, cocaine, heroin, N-formyl amphetamine, N-formyl methamphetamine, methamphetamine, 3, 4-methylenedioxymethamphetamine (MDMA), and pseudoephedrine—were evaluated on selected kitchen countertop surfaces. Methanol-dampened Whatman™ 40 filter paper wipes were used to collect samples from eleven surfaces including alkyd resin, ceramic tiles, glass, granite, laminate, limestone, marble, quartz compac, quartz real, soap stone, and stainless steel. The filter paper wipes were analyzed by a rapid three-minute UPLC-QTOF method, following ammonium acetate buffer (pH 5.8–6.2) extraction. The average percentage recoveries after 15 h of exposure to the surface materials tested, was found to be highest for cocaine and MDMA and lowest for amphetamine and methamphetamine. Among the eleven countertop surfaces, overall recoveries for marble were observed to be the least, whereas soapstone, quartz compac and stainless steel were among the highest. Scanning electron microscopic images of the surfaces provided a unique view of surface irregularities that potentially influenced drug recovery. Aging, migration, solvent composition, and volatility were examined. The variation in recovery of drugs was attributed to four key factors: compound volatility, surface composition, surface—compound interaction, and solvent composition.

  11. Knockdown of ventral tegmental area mu-opioid receptors in rats prevents effects of social defeat stress: Implications for amphetamine cross-sensitization, social avoidance, weight regulation and expression of brain-derived neurotrophic factor

    Science.gov (United States)

    Johnston, Caitlin E.; Herschel, Daniel; Lasek, Amy W.; Hammer, Ronald P.; Nikulina, Ella M.

    2014-01-01

    Social defeat stress causes social avoidance and long-lasting cross-sensitization to psychostimulants, both of which are associated with increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). Moreover, social stress upregulates VTA mu-opioid receptor (MOR) mRNA. In the VTA, MOR activation inhibits GABA neurons to disinhibit VTA dopamine neurons, thus providing a role for VTA MORs in the regulation of psychostimulant sensitization. The present study determined the effect of lentivirus-mediated MOR knockdown in the VTA on the consequences of intermittent social defeat stress, a salient and profound stressor in humans and rodents. Social stress exposure induced social avoidance and attenuated weight gain in animals with non-manipulated VTA MORs, but both these effects were prevented by VTA MOR knockdown. Rats with non-manipulated VTA MOR expression exhibited cross-sensitization to amphetamine challenge (1.0 mg/kg, i.p.), evidenced by a significant augmentation of locomotion. By contrast, knockdown of VTA MORs prevented stress-induced cross-sensitization without blunting the locomotor-activating effects of amphetamine. At the time point corresponding to amphetamine challenge, immunohistochemical analysis was performed to examine the effect of stress on VTA BDNF expression. Prior stress exposure increased VTA BDNF expression in rats with non-manipulated VTA MOR expression, while VTA MOR knockdown prevented stress-induced expression of VTA BDNF. Taken together, these results suggest that upregulation of VTA MOR is necessary for the behavioral and biochemical changes induced by social defeat stress. Elucidating VTA MOR regulation of stress effects on the mesolimbic system may provide new therapeutic targets for treating stress-induced vulnerability to substance abuse. PMID:25446676

  12. MCG101-induced cancer anorexia-cachexia features altered expression of hypothalamic Nucb2 and Cartpt and increased plasma levels of cocaine- and amphetamine-regulated transcript peptides.

    Science.gov (United States)

    Burgos, Jonathan R; Iresjö, Britt-Marie; Smedh, Ulrika

    2016-04-01

    The aim of the present study was to explore central and peripheral host responses to an anorexia-cachexia producing tumor. We focused on neuroendocrine anorexigenic signals in the hypothalamus, brainstem, pituitary and from the tumor per se. Expression of mRNA for corticotropin-releasing hormone (CRH), cocaine- and amphetamine-regulated transcript (CART), nesfatin-1, thyrotropin (TSH) and the TSH receptor were explored. In addition, we examined changes in plasma TSH, CART peptides (CARTp) and serum amyloid P component (SAP). C57BL/6 mice were implanted with MCG101 tumors or sham-treated. A sham-implanted, pair‑fed (PF) group was included to delineate between primary tumor and secondary effects from reduced feeding. Food intake and body weight were measured daily. mRNA levels from microdissected mouse brain samples were assayed using qPCR, and plasma levels were determined using ELISA. MCG101 tumors expectedly induced anorexia and loss of body weight. Tumor-bearing (TB) mice exhibited an increase in nesfatin-1 mRNA as well as a decrease in CART mRNA in the paraventricular area (PVN). The CART mRNA response was secondary to reduced caloric intake whereas nesfatin-1 mRNA appeared to be tumor-specifically induced. In the pituitary, CART and TSH mRNA were upregulated in the TB and PF animals compared to the freely fed controls. Plasma levels for CARTp were significantly elevated in TB but not PF mice whereas levels of TSH were unaffected. The plasma CARTp response was correlated to the degree of inflammation represented by SAP. The increase in nesfatin-1 mRNA in the PVN highlights nesfatin-1 as a plausible candidate for causing tumor-induced anorexia. CART mRNA expression in the PVN is likely an adaptation to reduced caloric intake secondary to a cancer anorexia-cachexia syndrome (CACS)‑inducing tumor. The MCG101 tumor did not express CART mRNA, thus the elevation of plasma CARTp is host derived and likely driven by inflammation.

  13. Amphetamine and environmentally induced hyperthermia differentially alter the expression of genes regulating vascular tone and angiogenesis in the meninges and associated vasculature.

    Science.gov (United States)

    Thomas, Monzy; George, Nysia I; Patterson, Tucker A; Bowyer, John F

    2009-10-01

    An amphetamine (AMPH) regimen that does not produce a prominent blood-brain barrier breakdown was shown to significantly alter the expression of genes regulating vascular tone, immune function, and angiogenesis in vasculature associated with arachnoid and pia membranes of the forebrain. Adult-male Sprague-Dawley rats were given either saline injections during environmentally-induced hyperthermia (EIH) or four doses of AMPH with 2 h between each dose (5, 7.5, 10, and 10 mg/kg d-AMPH, s.c.) that produced hyperthermia. Rats were sacrificed either 3 h or 1 day after dosing, and total RNA and protein was isolated from the meninges, arachnoid and pia membranes, and associated vasculature (MAV) that surround the forebrain. Vip, eNos, Drd1a, and Edn1 (genes regulating vascular tone) were increased by either EIH or AMPH to varying degrees in MAV, indicating that EIH and AMPH produce differential responses to enhance vasodilatation. AMPH, and EIH to a lesser extent, elicited a significant inflammatory response at 3 h as indicated by an increased MAV expression of cytokines Il1b, Il6, Ccl-2, Cxcl1, and Cxcl2. Also, genes related to heat shock/stress and disruption of vascular homeostasis such as Icam1 and Hsp72 were also observed. The increased expression of Ctgf and Timp1 and the decreased expression of Akt1, Anpep, and Mmp2 and Tek (genes involved in stimulating angiogenesis) from AMPH exposure suggest that angiogenesis was arrested or disrupted in MAV to a greater extent by AMPH compared to EIH. Alterations in vascular-related gene expression in the parietal cortex and striatum after AMPH were less in magnitude than in MAV, indicating less of a disruption of vascular homeostasis in these two regions. Changes in the levels of insulin-like growth factor binding proteins Igfbp1, 2, and 5 in MAV, compared to those in striatum and parietal cortex, imply an interaction between these regions to regulate the levels of insulin-like growth factor after AMPH damage. Thus, the

  14. Comparison of the global gene expression of choroid plexus and meninges and associated vasculature under control conditions and after pronounced hyperthermia or amphetamine toxicity.

    Science.gov (United States)

    Bowyer, John F; Patterson, Tucker A; Saini, Upasana T; Hanig, Joseph P; Thomas, Monzy; Camacho, Luísa; George, Nysia I; Chen, James J

    2013-03-05

    The meninges (arachnoid and pial membranes) and associated vasculature (MAV) and choroid plexus are important in maintaining cerebrospinal fluid (CSF) generation and flow. MAV vasculature was previously observed to be adversely affected by environmentally-induced hyperthermia (EIH) and more so by a neurotoxic amphetamine (AMPH) exposure. Herein, microarray and RT-PCR analysis was used to compare the gene expression profiles between choroid plexus and MAV under control conditions and at 3 hours and 1 day after EIH or AMPH exposure. Since AMPH and EIH are so disruptive to vasculature, genes related to vasculature integrity and function were of interest. Our data shows that, under control conditions, many of the genes with relatively high expression in both the MAV and choroid plexus are also abundant in many epithelial tissues. These genes function in transport of water, ions, and solutes, and likely play a role in CSF regulation. Most genes that help form the blood-brain barrier (BBB) and tight junctions were also highly expressed in MAV but not in choroid plexus. In MAV, exposure to EIH and more so to AMPH decreased the expression of BBB-related genes such as Sox18, Ocln, and Cldn5, but they were much less affected in the choroid plexus. There was a correlation between the genes related to reactive oxidative stress and damage that were significantly altered in the MAV and choroid plexus after either EIH or AMPH. However, AMPH (at 3 hr) significantly affected about 5 times as many genes as EIH in the MAV, while in the choroid plexus EIH affected more genes than AMPH. Several unique genes that are not specifically related to vascular damage increased to a much greater extent after AMPH compared to EIH in the MAV (Lbp, Reg3a, Reg3b, Slc15a1, Sct and Fst) and choroid plexus (Bmp4, Dio2 and Lbp). Our study indicates that the disruption of choroid plexus function and damage produced by AMPH and EIH is significant, but the changes may not be as pronounced as they are in

  15. Chiral separations of cathinone and amphetamine-derivatives: Comparative study between capillary electrochromatography, supercritical fluid chromatography and three liquid chromatographic modes.

    Science.gov (United States)

    Albals, Dima; Heyden, Yvan Vander; Schmid, Martin G; Chankvetadze, Bezhan; Mangelings, Debby

    2016-03-20

    The screening part of an earlier defined chiral separation strategy in capillary electrochromatography (CEC) was used for the separation of ten cathinone- and amphetamine derivatives. They were analyzed using 4 polysaccharide-based chiral stationary phases (CSPs), containing cellulose tris(3,5-dimethylphenylcarbamate) (ODRH), amylose tris(3,5-dimethylphenylcarbamate) (ADH), amylose tris(5-chloro-2-methylphenylcarbamate) (LA2), and cellulose tris(4-chloro-3-methylphenylcarbamate) (LC4) as chiral selectors. After applying the screening to each compound, ADH and LC4 showed the highest success rate. In a second part of the study, a comparison between CEC and other analytical techniques used for chiral separations i.e., supercritical fluid chromatography (SFC), polar organic solvent chromatography (POSC), reversed-phase (RPLC) and normal-phase liquid chromatography (NPLC), was made. For this purpose, earlier defined screening approaches for each technique were applied to separate the 10 test substances. This allowed an overall comparison of the success rates of the screening steps of the 5 techniques for these compounds. The results showed that CEC had a similar enantioselectivity rate as NPLC and RPLC, producing the highest number of separations (9 out of 10 racemates). SFC resolved 7 compounds, while POSC gave only 2 separations. On the other hand, the baseline separation success rates for NPLC and RPLC was better than for CEC. For a second comparison, the same chiral stationary phases as in the CEC screening were also tested with all techniques at their specific screening conditions, which allowed a direct comparison of the performance of CEC versus the same CSPs in the other techniques. This comparison revealed that RPLC was able to separate all tested compounds, and also produced the highest number of baseline separations on the CSP that were used in the CEC screening step. CEC and NPLC showed the same success rate: nine out of ten substances were separated. When

  16. The prognosis following amphetamine poisoning

    DEFF Research Database (Denmark)

    Horwitz, Henrik; Dalhoff, Kim P.; Klemp, Marc

    2017-01-01

    % CI (1.03-1.09)), opioid dependence (HR 2.88, 95% CI (1.42-5.85)), schizophrenia (HR 3.09,95% CI (1.63-5.86)), affective disorders (HR 2.65, 95% CI (1.44-4.90)) and HIV (HR 5.45, 95% CI (1.19-24.90)) were associated with a high mortality. Furthermore, a significant proportion of these patients...

  17. Repeated Administration of D-Amphetamine Induces Distinct Alterations in Behavior and Metabolite Levels in 129Sv and Bl6 Mouse Strains

    Directory of Open Access Journals (Sweden)

    Taavi Vanaveski

    2018-06-01

    Full Text Available The main goal of the study was to characterize the behavioral and metabolomic profiles of repeated administration (for 11 days of d-amphetamine (AMPH, 3 mg/kg i. p., indirect agonist of dopamine (DA, in widely used 129S6/SvEvTac (129Sv and C57BL/6NTac (Bl6 mouse strains. Acute administration of AMPH (acute AMPH induced significantly stronger motor stimulation in Bl6. However, repeated administration of AMPH (repeated AMPH caused stronger motor sensitization in 129Sv compared acute AMPH. Body weight of 129Sv was reduced after repeated saline and AMPH, whereas no change occurred in Bl6. In the metabolomic study, acute AMPH induced an elevation of isoleucine and leucine, branched chain amino acids (BCAA, whereas the level of hexoses was reduced in Bl6. Both BCAAs and hexoses remained on level of acute AMPH after repeated AMPH in Bl6. Three biogenic amines [asymmetric dimethylarginine (ADMA, alpha-aminoadipic acid (alpha-AAA, kynurenine] were significantly reduced after repeated AMPH. Acute AMPH caused in 129Sv a significant reduction of valine, lysophosphatidylcholines (lysoPC a C16:0, lysoPC a C18:2, lysoPC a C20:4, phosphatidylcholine (PC diacyls (PC aa C34:2, PC aa C36:2, PC aa C36:3, PC aa C36:4 and alkyl-acyls (PC ae C38:4, PC ae C40:4. However, repeated AMPH increased the levels of valine and isoleucine, long-chain acylcarnitines (C14, C14:1-OH, C16, C18:1, PC diacyls (PC aa C38:4, PC aa C38:6, PC aa C42:6, PC acyl-alkyls (PC ae C38:4, PC ae C40:4, PC ae C40:5, PC ae C40:6, PC ae C42:1, PC ae C42:3 and sphingolipids [SM(OHC22:1, SM C24:0] compared to acute AMPH in 129Sv. Hexoses and kynurenine were reduced after repeated AMPH compared to saline in 129Sv. The established changes probably reflect a shift in energy metabolism toward lipid molecules in 129Sv because of reduced level of hexoses. Pooled data from both strains showed that the elevation of isoleucine and leucine was a prominent biomarker of AMPH-induced behavioral sensitization

  18. Neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and cholecystokinin (CCK) in winter skate (Raja ocellata): cDNA cloning, tissue distribution and mRNA expression responses to fasting.

    Science.gov (United States)

    MacDonald, Erin; Volkoff, Hélène

    2009-04-01

    cDNAs encoding for neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and cholecystokinin (CCK) were cloned in an elasmobranch fish, the winter skate. mRNA tissue distribution was examined for the three peptides as well as the effects of two weeks of fasting on their expression. Skate NPY, CART and CCK sequences display similarities with sequences for teleost fish but in general the degree of identity is relatively low (50%). All three peptides are present in brain and in several peripheral tissues, including gut and gonads. Within the brain, the three peptides are expressed in the hypothalamus, telencephalon, optic tectum and cerebellum. Two weeks of fasting induced an increase in telencephalon NPY and an increase in CCK in the gut but had no effects on hypothalamic NPY, CART and CCK, or on telencephalon CART. Our results provide basis for further investigation into the regulation of feeding in winter skate.

  19. Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens.

    Science.gov (United States)

    Rakovska, Angelina; Baranyi, Maria; Windisch, Katalin; Petkova-Kirova, Polina; Gagov, Hristo; Kalfin, Reni

    2017-09-01

    CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [ 3 H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal

  20. Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry.

    Science.gov (United States)

    Meyer, Markus R; Wilhelm, Jens; Peters, Frank T; Maurer, Hans H

    2010-06-01

    In recent years, a new class of designer drugs has appeared on the drugs of abuse market in many countries, namely, the so-called beta-keto (bk) designer drugs such as mephedrone (bk-4-methylmethamphetamine), butylone (bk-MBDB), and methylone (bk-MDMA). The aim of the present study was to identify the metabolites of mephedrone in rat and human urine using GC-MS techniques and to include mephedrone, butylone, and methylone within the authors' systematic toxicological analysis (STA) procedure. Six phase I metabolites of mephedrone were detected in rat urine and seven in human urine suggesting the following metabolic steps: N-demethylation to the primary amine, reduction of the keto moiety to the respective alcohol, and oxidation of the tolyl moiety to the corresponding alcohols and carboxylic acid. The STA procedure allowed the detection of mephedrone, butylone, methylone, and their metabolites in urine of rats treated with doses corresponding to those reported for abuse of amphetamines. Besides macro-based data evaluation, an automated evaluation using the automated mass spectral deconvolution and identification system was performed. Mephedrone and butylone could be detected also in human urine samples submitted for drug testing. Assuming similar kinetics in humans, the described STA procedure should be suitable for proof of an intake of the bk-designer drugs in human urine.

  1. Why does the Y326I mutant of monoamine oxidase B decompose an endogenous amphetamine at a slower rate than the wild type enzyme? Reaction step elucidated by multiscale molecular simulations.

    Science.gov (United States)

    Pregeljc, Domen; Jug, Urška; Mavri, Janez; Stare, Jernej

    2018-02-07

    This work investigates the Y326I point mutation effect on the kinetics of oxidative deamination of phenylethylamine (PEA) catalyzed by the monoamine oxidase B (MAO B) enzyme. PEA is a neuromodulator capable of affecting the plasticity of the brain and is responsible for the mood enhancing effect caused by physical exercise. Due to a similar functionality, PEA is often regarded as an endogenous amphetamine. The rate limiting step of the deamination was simulated at the multiscale level, employing the Empirical Valence Bond approach for the quantum treatment of the involved valence states, whereas the environment (solvated protein) was represented with a classical force field. A comparison of the reaction free energy profiles delivered by simulation of the reaction in the wild type MAO B and its Y326I mutant yields an increase in the barrier by 1.06 kcal mol -1 upon mutation, corresponding to a roughly 6-fold decrease in the reaction rate. This is in excellent agreement with the experimental kinetic studies. Inspection of simulation trajectories reveals possible sources of the point mutation effect, namely vanishing favorable electrostatic interactions between PEA and a Tyr326 side chain and an increased amount of water molecules at the active site due to the replacement of tyrosine by a less spacious isoleucine residue, thereby increasing the dielectric shielding of the catalytic environment provided by the enzyme.

  2. Activations of c-fos/c-jun signaling are involved in the modulation of hypothalamic superoxide dismutase (SOD) and neuropeptide Y (NPY) gene expression in amphetamine-mediated appetite suppression

    International Nuclear Information System (INIS)

    Hsieh, Y.-S.; Yang, S.-F.; Chiou, H.-L.; Kuo, D.-Y.

    2006-01-01

    Amphetamine (AMPH) is known as an anorectic agent. The mechanism underlying the anorectic action of AMPH has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an appetite stimulant in the brain. This study was aimed to examine the molecular mechanisms behind the anorectic effect of AMPH. Results showed that AMPH treatment decreased food intake, which was correlated with changes of NPY mRNA level, but increased c-fos, c-jun and superoxide dismutase (SOD) mRNA levels in hypothalamus. To determine if c-fos or c-jun was involved in the anorectic response of AMPH, infusions of antisense oligonucleotide into the brain were performed at 1 h before daily AMPH treatment in freely moving rats, and the results showed that c-fos or c-jun knockdown could block this anorectic response and restore NPY mRNA level. Moreover, c-fos or c-jun knockdown could partially block SOD mRNA level that might involve in the modulation of NPY gene expression. It was suggested that c-fos/c-jun signaling might involve in the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression

  3. Evidence of a local negative role for cocaine and amphetamine regulated transcript (CART, inhibins and low molecular weight insulin like growth factor binding proteins in regulation of granulosa cell estradiol production during follicular waves in cattle

    Directory of Open Access Journals (Sweden)

    Ireland James J

    2006-04-01

    Full Text Available Abstract The ability of ovarian follicles to produce large amounts of estradiol is a hallmark of follicle health status. Estradiol producing capacity is lost in ovarian follicles before morphological signs of atresia. A prominent wave like pattern of growth of antral follicles is characteristic of monotocous species such as cattle, horses and humans. While our knowledge of the role of pituitary gonadotropins in support of antral follicle growth and development is well established, the intrinsic factors that suppress estradiol production and may help promote atresia during follicular waves are not well understood. Numerous growth factors and cytokines have been reported to suppress granulosa cell estradiol production in vitro, but the association of expression of many such factors in vivo with follicle health status and their physiological significance are not clear. The purpose of this review is to discuss the in vivo and in vitro evidence supporting a local physiological role for cocaine and amphetamine regulated transcript, inhibins and low molecular weight insulin like growth factor binding proteins in negative regulation of granulosa cell estradiol production, with emphasis on evidence from the bovine model system.

  4. Amphetamine-Type-Stimulants (ATS) Use and Homosexuality-Related Enacted Stigma Are Associated With Depression Among Men Who Have Sex With Men (MSM) in Two Major Cities in Vietnam in 2014.

    Science.gov (United States)

    Vu, Nga Thi Thu; Holt, Martin; Phan, Huong Thi Thu; La, Lan Thi; Tran, Gioi Minh; Doan, Tung Thanh; Nguyen, Trang Nguyen Nhu; de Wit, John

    2017-09-19

    Men who have sex with men (MSM) are disproportionately affected by mental health concerns, including depression. Amphetamine-type-stimulants (ATS) use and homosexuality-related stigma and discrimination have been found associated with depression among MSM. To assess the prevalence of depression and its associations with ATS use and homosexuality-related stigma and discrimination among MSM in Vietnam. 622 MSM were conveniently recruited in Hanoi and Ho Chi Minh city, Vietnam, from September to December 2014. We collected information on demographic characteristics, ATS, alcohol and other drug use, sexual behaviors, homosexuality-related and discrimination stigma, and sexual sensation-seeking. Depression and suicidal thoughts were assessed by the Patient Health Questionnaire (PHQ-9). We assessed associations of depression with ATS use and homosexuality-related stigma and discrimination using logistic regression. Of 622 sampled MSM, 11.3% were classified as having major depression, 9.8% reported any suicidal thoughts in the last two weeks, 30.4% ever had used any ATS, 88.8% ever ad drank alcohol and 21.5% had ever used any other drugs. In multivariate analysis, depression was significantly associated with ATS use (Adjusted Odds Ratio [AOR: 2.20; (95% Confidence Interval (CI): 1.32-3.67], younger age of sexual debut with another man (AOR: 0.09; 95% CI: 0.02-0.50), and greater enacted homosexuality-related stigma (AOR: 1.97; 95% CI: 1.19-3.26). We found a moderate prevalence of depression among sampled MSM, which was associated with ATS use and enacted homosexuality-related stigma. We recommend integrating assessment and interventions regarding depression and methamphetamine use into gay-friendly, culturally adapted holistic HIV prevention for MSM in Vietnam.

  5. Cocaine- and amphetamine-regulated transcript peptide in the nucleus accumbens shell inhibits cocaine-induced locomotor sensitization to transient over-expression of α-Ca2+ /calmodulin-dependent protein kinase II.

    Science.gov (United States)

    Xiong, Lixia; Meng, Qing; Sun, Xi; Lu, Xiangtong; Fu, Qiang; Peng, Qinghua; Yang, Jianhua; Oh, Ki-Wan; Hu, Zhenzhen

    2018-01-04

    Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter that attenuates cocaine-induced locomotor activity when injected into the nucleus accumbens (NAc). Our previous work first confirmed that the inhibitory mechanism of the CART peptide on cocaine-induced locomotor activity is related to a reduction in cocaine-enhanced phosphorylated Ca 2+ /calmodulin-dependent protein kinaseIIα (pCaMKIIα) and the enhancement of cocaine-induced D3R function. This study investigated whether CART peptide inhibited cocaine-induced locomotor activity via inhibition of interactions between pCaMKIIα and the D3 dopamine receptor (D3R). We demonstrated that lentivirus-mediated gene transfer transiently increased pCaMKIIα expression, which peaked at 10 days after microinjection into the rat NAc shell, and induced a significant increase in Ca 2+ influx along with greater behavioral sensitivity in the open field test after intraperitoneal injections of cocaine (15 mg/kg). However, western blot analysis and coimmunoprecipitation demonstrated that CART peptide treatment in lentivirus-transfected CaMKIIα-over-expressing NAc rat tissues or cells prior to cocaine administration inhibited the cocaine-induced Ca 2+ influx and attenuated the cocaine-increased pCaMKIIα expression in lentivirus-transfected CaMKIIα-over-expressing cells. CART peptide decreased the cocaine-enhanced phosphorylated cAMP response element binding protein (pCREB) expression via inhibition of the pCaMKIIα-D3R interaction, which may account for the prolonged locomotor sensitization induced by repeated cocaine treatment in lentivirus-transfected CaMKIIα-over-expressing cells. These results provide strong evidence for the inhibitory modulation of CART peptide in cocaine-induced locomotor sensitization. © 2018 International Society for Neurochemistry.

  6. Cocaine- and amphetamine-regulated transcript peptide and calcium binding proteins immunoreactivity in the deep layers of the superior colliculus of the guinea pig: Implications for multisensory and visuomotor processing.

    Science.gov (United States)

    Najdzion, Janusz

    2018-03-01

    The superior colliculus (SC) of mammals is a midbrain center, that can be subdivided into the superficial (SCs) and deep layers (SCd). In contrast to the visual SCs, the SCd are involved in multisensory and motor processing. This study investigated the pattern of distribution and colocalization of cocaine- and amphetamine-regulated transcript peptide (CART) and three calcium-binding proteins (CaBPs) i.e. calbindin (CB), calretinin (CR) and parvalbumin (PV) in the SCd of the guinea pig. CART labeling was seen almost exclusively in the neuropil and fibers, which differed in regard to morphology and location. CART-positive neurons were very rare and restricted to a narrow area of the SCd. The most intense CART immunoreactivity was observed in the most dorsally located sublayer of the SCd, which is anatomically and functionally connected with the SCs. CART immunoreactivity in the remaining SCd was less intensive, but still relatively high. This characteristic pattern of immunoreactivity indicates that CART as a putative neurotransmitter or neuromodulator may play an important role in processing of visual information, while its involvement in the auditory and visuomotor processing is less significant, but still possible. CaBPs-positive neurons were morphologically diverse and widely distributed throughout all SCd. From studied CaBPs, CR showed a markedly different distribution compared to CB and PV. Overall, the patterns of distribution of CB and PV were similar in the entire SCd. Consequently, the complementarity of these patterns in the guinea pig was very weak. Double immunostaining revealed that CART did not colocalize with either CaBPs, which suggested that these neurochemical substances might not coexist in the multisensory and visuomotor parts of the SC. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Uso de anfetaminas por motoristas de caminhão em rodovias do Estado de São Paulo: um risco à ocorrência de acidentes de trânsito? Amphetamine use by truck drivers on highways of Sao Paulo State: a risk for the occurrence of traffic accidents?

    Directory of Open Access Journals (Sweden)

    Mauricio Yonamine

    2013-05-01

    Full Text Available No Brasil, é comum o uso de anfetaminas por motoristas de caminhão, o que pode culminar na ocorrência de acidentes de trânsito. O objetivo deste artigo é estimar a prevalência do uso de anfetaminas entre caminhoneiros. Motoristas (N = 134 foram abordados em duas rodovias do Estado de São Paulo e solicitados a responder um questionário, assim como a fornecer uma amostra de urina para realização de análises toxicológicas. Todos os dados foram analisados em Stata 8.0. Todos os participantes eram do sexo masculino, de idade média de 40,8 anos e de baixa escolaridade. A presença de anfetaminas foi detectada em 10,8% das amostras de urina, cujo uso foi justificado para manter a vigília durante o trabalho. O uso de anfetaminas foi detectado entre caminhoneiros em rodovias de São Paulo. Cessado o efeito estimulante, a sonolência advinda de uma possível privação de sono diminui a atenção e o bom desempenho na direção, predispondo o condutor aos acidentes de trânsito e seus custos relacionados.The use of amphetamines in Brazil is common among truck drivers, which may be an important factor in the occurrence of traffic accidents. This article seeks to estimate the prevalence of amphetamine use among truck drivers. Drivers (N = 134 were stopped on two different highways in Sao Paulo state and they were asked to answer a questionnaire and provide a urine sample for toxicological analysis. All data were analyzed on Stata 8.0. All participants were males with low levels of schooling, whose mean age was 40.8 years. The presence of amphetamines was detected in 10.8% of all urine samples collected, being commonly justified in order to make truck drivers able to maintain their state of awareness. Amphetamine use was detected among truck drivers on Sao Paulo highways. The problem is that when the stimulant effects wear off, sleepiness due to sleep deprivation reduces concentration and good driver performance, making drivers vulnerable to

  8. Protocol of a cluster randomised stepped-wedge trial of behavioural interventions targeting amphetamine-type stimulant use and sexual risk among female entertainment and sex workers in Cambodia.

    Science.gov (United States)

    Page, Kimberly; Stein, Ellen S; Carrico, Adam W; Evans, Jennifer L; Sokunny, Muth; Nil, Ean; Ngak, Song; Sophal, Chhit; McCulloch, Charles; Maher, Lisa

    2016-05-09

    HIV risk among female entertainment and sex workers (FESW) remains high and use of amphetamine-type stimulants (ATS) significantly increases this risk. We designed a cluster randomised stepped wedge trial (The Cambodia Integrated HIV and Drug Prevention Implementation (CIPI) study) to test sequentially delivered behavioural interventions targeting ATS use. The trial combines a 12-week Conditional Cash Transfer (CCT) intervention with 4 weeks of cognitive-behavioural group aftercare (AC) among FESW who use ATS. The primary goal is to reduce ATS use and unprotected sex among FESW. The CCT+AC intervention is being implemented in 10 provinces where order of delivery was randomised. Outcome assessments (OEs) including biomarkers and self-reported measures of recent sexual and drug use behaviours are conducted prior to implementation, and at three 6-month intervals after completion. Consultation with multiple groups and stakeholders on implementation factors facilitated acceptance and operationalisation of the trial. Statistical power and sample size calculations were based on expected changes in ATS use and unprotected sex at the population level as well as within subjects. Ethical approvals were granted by the Cambodia National Ethics Committee; University of New Mexico; University of California, San Francisco; and FHI360. The trial is registered with ClinicalTrials.gov. Dissemination of process indicators during the multiyear trial is carried out through annual in-country Stakeholder Meetings. Provincial 'Close-Out' forums are held at the conclusion of data collection in each province. When analysis is completed, dissemination meetings will be held in Cambodia with stakeholders, including community-based discussion sessions, policy briefs and results published and presented in the HIV prevention scientific journals and conferences. CIPI is the first trial of an intervention to reduce ATS use and HIV risk among FESW in Cambodia. Will inform both CCT+AC implementation

  9. Amphetamine increases errors during episodic memory retrieval.

    Science.gov (United States)

    Ballard, Michael Edward; Gallo, David A; de Wit, Harriet

    2014-02-01

    Moderate doses of stimulant drugs are known to enhance memory encoding and consolidation, but their effects on memory retrieval have not been explored in depth. In laboratory animals, stimulants seem to improve retrieval of emotional memories, but comparable studies have not been carried out in humans. In the present study, we examined the effects of dextroamphetamine (AMP) on retrieval of emotional and unemotional stimuli in healthy young adults, using doses that enhanced memory formation when administered before encoding in our previous study. During 3 sessions, healthy volunteers (n = 31) received 2 doses of AMP (10 and 20 mg) and placebo in counterbalanced order under double-blind conditions. During each session, they first viewed emotional and unemotional pictures and words in a drug-free state, and then 2 days later their memory was tested, 1 hour after AMP or placebo administration. Dextroamphetamine did not affect the number of emotional or unemotional stimuli remembered, but both doses increased recall intrusions and false recognition. Dextroamphetamine (20 mg) also increased the number of positively rated picture descriptions and words generated during free recall. These data provide the first evidence that therapeutic range doses of stimulant drugs can increase memory retrieval errors. The ability of AMP to positively bias recollection of prior events could contribute to its potential for abuse.

  10. physiological effects of the amphetamines during exercise

    African Journals Online (AJOL)

    Oxygen consumption, heart rate, minute ventilation and blood lactate were measured on two champion cyclisTs at work rates from 45 to 362 W (2 000 - 16 000 ft-Ib / min) on a bicycle ergometer after administration of a placebo and after 10 mg of methamphetamine, withoUT their know- ledge of which was given.

  11. Physiological effects of the amphetamines during exercise ...

    African Journals Online (AJOL)

    Oxygen consumption, heart rate, minute ventilation and blood lactate were measured on two champion cyclists at work rates from 45 to 362 W (2 000 - 16 000 ft-Ib / min) on a bicycle ergometer after administration of a placebo and after 10 mg of methamphetamine, without their knowledge of which was given. No differences ...

  12. Methamphetamine and the expanding complications of amphetamines.

    OpenAIRE

    Albertson, T E; Derlet, R W; Van Hoozen, B E

    1999-01-01

    During the past 10 years, the use of methamphetamine has increased rapidly in the West and throughout the United States. Because of this increase, our attention has focused on methamphetamine's toxicity. Methamphetamine and related compounds generate many of the same toxic effects as cocaine. Because of methamphetamine's widespread use, clinicians should be familiar with its medical effects and toxicity and with treatment options for acute and long-term effects of methamphetamine abuse.

  13. Stimulant ADHD Medications -- Methylphenidate and Amphetamines

    Science.gov (United States)

    ... g., to help study or boost grades in school; see box). Stimulant ADHD Medications • January 2014 • Page 1 Because they may ... taken by people who do not actually have ADHD. Also, research has shown that ... have lower GPAs in high school and college than those who don’t. How ...

  14. Use and abuse of amphetamine-type stimulants in the United States of America Uso y abuso de estimulantes anfetamínicos en Estados Unidos de América

    Directory of Open Access Journals (Sweden)

    G. Cajetan Luna

    2001-02-01

    Full Text Available In recent years the United States of America has experienced economic growth, low unemployment, low inflation, and technological advances. However, coexisting with these favorable conditions are underlying and underaddressed social inequalities that may have an impact on patterns of use and abuse of substances, including amphetamine-type stimulants (ATSs. For example, since 1975 most of the increase in national income has benefited people who are at the top 20% of the income range. There are disparities between those who do have and those who do not have the skills needed to thrive in a technologically dependent society, and the gap may be widening. New patterns of substance abuse being seen in the United States may in part be explained by the increasing competition to survive financially and interpersonally, the need that those failing to adapt to rapid technological change have to escape psychologically and existentially, and the desire of the socially alienated and disenfranchised to self-medicate with ATSs and at least temporarily avoid social and economical inequities. According to the 1998 National Household Survey on Drug Abuse, an estimated 13.6 million Americans were users of illicit drugs (1. This number is less than the 13.9 million estimated for 1997, and by comparison less than the highest level, in 1979, when the estimate was 25 million. With respect to stimulants in particular, the overall level of usage has remained constant, but increases have been observed in specific high-risk populations, who need focused outreach and intervention efforts. This article will focus on ATSs in the United States, including relevant demographic and cultural dimensions of their use and abuse, and suggested directions for future ATS research and program development.En los Estados Unidos de América, la popularidad de los compuestos anfetamínicos de consumo legal e ilegal, junto con las prácticas de uso y abuso que con ellos se asocian, han variado

  15. Desenvolvimento e validação de um método cromatográfico em fase gasosa para análise da 3,4-metilenodioximetanfetamina (ecstasy e outros derivados anfetamínicos em comprimidos Development and validation of a gas chromatography method for determination of ecstasy and amphetamines derivatives in tablets

    Directory of Open Access Journals (Sweden)

    Marcelo Carvalho Lasmar

    2007-06-01

    Full Text Available O uso abusivo das anfetaminas e seus derivados vêm aumentando dramaticamente nos últimos anos em diversas regiões do mundo, notando-se especial utilização do Ecstasy. A análise de amostras da droga apreendidas nas ruas evidenciou, além da presença de MDMA (3,4-metilenodioximetanfetamina, componente principal da droga, outras feniletilaminas, como a MDA (3,4-metilenodioxanfetamina e MDEA (metilenodioximetiletilanfetamina este último também conhecido como a droga Eve, ainda pouco difundida no Brasil. O objetivo do presente trabalho foi desenvolver e validar um método analítico confiável, prático e acessível aos laboratórios de toxicologia, de médio e pequeno porte, no Brasil e em países em desenvolvimento, para identificação separada do MDMA, MDA e MDEA. A cromatografia em fase gasosa utilizando-se coluna capilar e detector de ionização de chama foi a técnica escolhida. O método analítico apresentou para os três analitos de interesse, faixa ampla de linearidade (1,0 a 500,0 µg/mL; limites de quantificação de 1,0 µg/mL e coeficientes de variação intra e interensaio inferiores a 9,5%. Os limites de detecção estabelecidos foram 0,7 µg/mL, 0,8 µg/mL e 0,6 µg/mL, respectivamente para o MDMA, MDA e MDEA. O método foi seletivo na presença de epinefrina, cocaína, anfetamina, ácido acetilsalisílico, metanfetamina, ácido dietilbarbitúrico, p-aminobenzoil dietilbarbitúrico, paracetamol e cafeína.The abusive use of the amphetamine derivative ecsyasy in the world come increasing in the last years. Many tablets samples kept on the streets shown the presence not only of the MDMA- 3,4-methylenedioxymethamphetamine, the main drug component but also of the MDA - 3,4- methylenedioxyamphetamine and MDEA - 3,4-methylenedioxymethylethylamphetamine. The present study sought to develop and validate an analytical method for determination of MDMA, MDA and MDEA in tablets to be accessible for the most small or medium

  16. and amphetamine-regulated transcripts and their associations with ...

    Indian Academy of Sciences (India)

    Srinivas

    and control of digestion and metabolism (Okumura et al. 2000; Aja et al 2001; ..... the mutation of amino acid. Nevertheless .... Diabetes 50 2157–2160. Henderson C R ... insulin secretion and glucose intolerance, altered beta cell morphology ...

  17. Range of application of J-123-amphetamine in neurology

    International Nuclear Information System (INIS)

    Podreka, I.; Hoell, K.; Dal-Bianco, P.; Mamoli, B.; Roszucky, A.; Angelberger, P.

    1984-01-01

    Using a dual head rotating scintillation camera (Siemens Rota ZLC 37) IMP-SPECT studies of the brain were carried out in 100 patients with different neurologic disorders (apoplexy, epilepsy) and in 5 normal subjects. In 90 cases CT of the skull was equally ordered. In patients with epilepsy EEGs were recorded at the time of SPECT. The results obtained with these procedures were compared. In patients with compromised cerebral blood flow IMP studies consistently showed lesions compatible with the clinical signs and symptoms, while the CT scan was often normal in the presence of transient cerebrovascular episodes. In about 70% of patients with epilepsy a lesion was demonstrated by both EEG and IMP so that epileptogenic foci were successfully visualized. In 2 instances acoustic stimulation was associated with a regionally increased IMP uptake in the temporal lobe area bilaterally. Using the microsphere model described by Kuhl and associates, an attempt was made to quantify cerebral blood flow. For this purpose a scatter correction was introduced before reconstructing the images (filtered back projection). In this manner clinically relevant flow levels were computed in 10 cases. (Author)

  18. Regulation of dopamine transporter trafficking by intracellular amphetamine

    DEFF Research Database (Denmark)

    Kahlig, Kristopher M; Lute, Brandon J; Wei, Yuqiang

    2006-01-01

    -induced cell surface DAT redistribution may result in long-lasting changes in DA homeostasis. The molecular mechanism by which AMPH induces trafficking is not clear. Because AMPH is a substrate, we do not know whether extracellular AMPH stimulates trafficking through its interaction with DAT and subsequent...... alteration in DAT function, thereby triggering intracellular signaling or whether AMPH must be transported and then act intracellularly. In agreement with our previous studies, extracellular AMPH caused cytosolic redistribution of the wild-type human DAT (WT-hDAT). However, AMPH did not induce cytosolic...... redistribution in an uptake-impaired hDAT (Y335A-hDAT) that still binds AMPH. The divalent cation zinc (Zn(2+)) inhibits WT-hDAT activity, but it restores Y335A-hDAT uptake. Coadministration of Zn(2+) and AMPH consistently reduced WT-hDAT trafficking but stimulated cytosolic redistribution of Y335A...

  19. Enantiomer profiling of high loads of amphetamine and MDMA in communal sewage: a Dutch perspective

    NARCIS (Netherlands)

    Emke, E.; Evans, S; Kasprzyk-Hordern, B.; de Voogt, P.

    2014-01-01

    Analysis of wastewater with an aim of community-wide estimation of drug use is a new and very promising approach. Until now it was very difficult to determine if mass loads of studied drugs were actually originating from consumption, or disposal of unused drugs or production waste. This uncertainty

  20. Clinical characteristics and outcome of heart failure and captagon amphetamine use: An observational prospective study

    Directory of Open Access Journals (Sweden)

    Abdelfatah A. Elasfar

    2014-03-01

    Conclusios: Captagon use was found to be an independent risk factor of death and other morbidities in patients presented with cardiomyopathy and acute heart failure. Our study underscores the importance of improving education concerning the cardiac risks of captagon use.

  1. Cocaine- and amphetamine-regulated transcript (CART) peptide specific binding in pheochromocytoma cells PC12

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Maixnerová, Jana; Matyšková, Resha; Haugvicová, Renata; Šloncová, Eva; Elbert, Tomáš; Slaninová, Jiřina; Železná, Blanka

    2007-01-01

    Roč. 559, 2/3 (2007), s. 109-114 ISSN 0014-2999 R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514; CEZ:AV0Z50200510 Keywords : radioligand binding * CART * PC12 cells * food intake Subject RIV: CE - Biochemistry Impact factor: 2.376, year: 2007

  2. Strukturně-aktivní studie fragmentů peptidu "cocaine - and amphetamine regulated transcript"

    Czech Academy of Sciences Publication Activity Database

    Maixnerová, Jana; Blokešová, Darja; Železná, Blanka; Maletínská, Lenka

    2008-01-01

    Roč. 102, č. 5 (2008), s. 384-384 ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků. Konference Sigma-Aldrich /8./. 10.06.2008-13.06.2008, Devět skal - Žďárské vrchy] R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506 Keywords : CART peptide * fragments * binding * PC12 cells Subject RIV: CE - Biochemistry

  3. Peptid CART (cocaine- and amphetamine- regulated transcript) v signalizaci buněk PC12

    Czech Academy of Sciences Publication Activity Database

    Nagelová, Veronika; Železná, Blanka; Maletínská, Lenka

    2014-01-01

    Roč. 108, č. 5 (2014), s. 543 ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků /14./. 13.05.2014-16.05.2014, Milovy] R&D Projects: GA ČR GAP303/10/1368 Institutional support: RVO:61388963 Keywords : peptide CART * PC12 * c-Jun * SAPK/JNK Subject RIV: CE - Biochemistry

  4. Structure-activity relationship of CART (cocaine- and amphetamine-regulated transcript) peptide fragments

    Czech Academy of Sciences Publication Activity Database

    Maixnerová, Jana; Hlaváček, Jan; Blokešová, Darja; Kowalczyk, W.; Elbert, Tomáš; Šanda, Miloslav; Blechová, Miroslava; Železná, Blanka; Slaninová, Jiřina; Maletínská, Lenka

    2007-01-01

    Roč. 28, č. 10 (2007), s. 1945-1953 ISSN 0196-9781 R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506 Keywords : CART peptide * fragments * binding * PC12 cells Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.368, year: 2007

  5. Pathophysiologic study of chronic infarcts with I-123 isopropyl iodo-amphetamine (IMP)

    DEFF Research Database (Denmark)

    Raynaud, C; Rancurel, G; Samson, Y

    1987-01-01

    Seventeen chronic cerebral infarcts were investigated by a highly sensitive, dedicated brain single photon emission computerized tomography system using 123I-isopropyl iodoamphetamine (IMP) and 133Xe. IMP uptake was measured 10 minutes, 2 hours, and 5 hours after injection, and regional cerebral...... blood flow was measured with 133Xe. In 4 cases a positron emission tomography system was used to measure the rCBF and the regional metabolic rate of oxygen with C15O2 and 15O2. The results obtained allowed us to identify 2 abnormal zones. One, the "central area," was characterized by a severe decrease...... ischemic neuronal loss. The results stress the important role played by the peripheral area, which may be useful in establishing the prognosis and evaluating the efficacy of therapy in individual stroke cases....

  6. Functional brain imaging with I123-amphetamine. First experience in the Netherlands

    NARCIS (Netherlands)

    de Bruïne, J. F.; van Royen, E. A.; van Weeren, F.; vd Weel, F. A.; Reiffers, S.; Verbeeten, B. W.; Krens, H.; Hijdra, A.; Limburg, M.

    1986-01-01

    Single Photon Emission Computed Tomography (SPECT) has been used in the last five years as a method for cerebral bloodflow imaging, especially in cerebral infarction. In this study the first experiences in the Netherlands are presented. In 57.6% of our patients lesions, defined by SPECT were larger

  7. Effect of Low Amphetamine Doses on Cardiac Responses to Emotional Stress in Aged Rats

    NARCIS (Netherlands)

    Nyakas, Csaba; Buwalda, Bauke; Luiten, Paul G.M.; Bohus, Bela

    1992-01-01

    In young Wistar rats conditioned emotional stress can be characterized by a learned bradycardiac response to an inescapable footshock. In aged rats this bradycardiac response is attenuated and accompanied by suppressed behavioral arousal in response to novelty. In the present study, cardiac

  8. NTP-CERHR EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF AMPHETAMINE AND METHAMPHETAMINE.

    Science.gov (United States)

    A manuscript describes the results of an expert panel meeting of the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR). The purpose CERHR is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects ...

  9. Amphetamines, Barbiturates and Hallucinogens; An Analysis of Use, Distribution, and Control. Final Report.

    Science.gov (United States)

    McGlothlin, William H.

    This report is the third of three monographs to provide perspectives on the use, distribution, and control of illicit drugs. The first, conducted in 1971, described the prevalence, use patterns, sources, distribution, and economics of the marihuana market. The second (1972) estimated the cost, benefits, and potential of approaches to narcotic…

  10. Prenatal Tetrahydrocannabinol (THC) alters cognitive function and amphetamine response from weaning to adulthood in the rat

    OpenAIRE

    Silva, Lindsay; Zhao, Ning; Popp, Susanna; Dow-Edwards, Diana

    2011-01-01

    Research suggests that not only is marijuana use prevalent among women of reproductive age, but a significant number of women continue to use marijuana and its derivatives throughout pregnancy. Many studies have shown, in both humans and animals, that marijuana exposure during adolescence and adulthood is detrimental to normal cognition and memory. In this study, we examined the effects of daily intravenous injections of 0.15mg/kg Δ9-tetrahydrocannabinol (THC), given to pregnant dams througho...

  11. The acetylcholinesterase inhibitor galantamine inhibits d-amphetamine-induced psychotic-like behavior in Cebus monkeys

    DEFF Research Database (Denmark)

    Andersen, Maibritt B; Werge, Thomas; Fink-Jensen, Anders

    2007-01-01

    Cholinergic receptors (AChR) are reported altered in brains from schizophrenic patients, and a growing body of evidence suggests that muscarinic receptor agonists exhibit antipsychotic potential. Centrally acting selective muscarinic receptor agonists are currently not available for clinical use,...

  12. Applications and diagnostic value of cerebral scintiscanning using 123I-amphetamine

    International Nuclear Information System (INIS)

    Eibach, E.; Feine, U.; Kaiser, W.; Diener, H.C.; Petersen, D.

    1985-01-01

    123 I-IMP is a new radiopharmaceutical for direct cerebral scintiscanning, characterized by its ability to cross the blood-brain barrier and its accumulation in the brain. Present clinical indications are illustrated by examples (disturbances of cerebral blood flow, epilepsy, organic psychosyndrome). Single photon emission computerized tomography (SPECT) permits imaging in three planes (cantho-meatal, frontal, sagittal), although it lacks the morphological quality of TCT or NMR images. The new substance may open up new perspectives in neurophysiology and neuropharmacology. (orig.) [de

  13. Applications and diagnostic value of cerebral scintiscanning using /sup 123/I-amphetamine

    Energy Technology Data Exchange (ETDEWEB)

    Eibach, E.; Feine, U.; Kaiser, W.; Diener, H.C.; Petersen, D.

    1985-02-01

    /sup 123/I-IMP is a new radiopharmaceutical for direct cerebral scintiscanning, characterized by its ability to cross the blood-brain barrier and its accumulation in the brain. Present clinical indications are illustrated by examples (disturbances of cerebral blood flow, epilepsy, organic psychosyndrome). Single photon emission computerized tomography (SPECT) permits imaging in three planes (cantho-meatal, frontal, sagittal), although it lacks the morphological quality of TCT or NMR images. The new substance may open up new perspectives in neurophysiology and neuropharmacology.

  14. Spect with 123 I-amphetamine as a diagnostic aid for neurogical diseases

    International Nuclear Information System (INIS)

    Fill, H.; Vogl, G.; Zechmann, W.; Gerstenbrand, F.; Riccabona, G.

    1984-01-01

    In the past years computer tomography and Doppler sonography have reduced the importance of radionuclide studies in the diagnosis of neurologic disorders. However, a new family of tracers has recently been developed for tomographic imaging of cerebral blood flow. To establish the value of this new method 44 patients with neurologic disorders have sofar been investigated. As the number of patients was relatively small for drawing definitive conclusions on the usefulness of the procedure in a great variety of neurologic conditions, patients were referred for imaging without disclosure of the diagnosis. The data obtained were subsequently compared to the clinical and other findings. Sofar patients with TIA, PRIND, brain infarction, ICH, SAB, epilepsy, migraine, decerebrate syndrome and CO intoxication were examined. The studies, which were originally confined to patients with cerebral infarction, consistently showed a close correlation with CT findings, with hypoperfused areas invariably exceeding the size of the structural lesions. In clinically manifest TIA and PRIND with normal CT compromised flow in the affected areas was noted throughout. Similarly, a good agreement was seen in 'migraine accompagnee'. In patients after SAB areas of angiospastic hypoperfusion were recognizable. Functional deficits associated with CO intoxication and decerebrate syndrome were much more expensive than the morphological lesions seen on CT. Results obtained todate suggest that SPECT is useful in complementing existing studies for the diagnosis of neurologic disorders. (Author)

  15. Feeding-related effects of cart (cocaine and amphetamine regulated transcript) peptides and cholecystokinin in mouse obese models

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Maixnerová, Jana; Toma, Resha Shamas; Haugvicová, Renata; Slaninová, Jiřina; Železná, Blanka

    2006-01-01

    Roč. 12, Supplement (2006), s. 178 ISSN 1075-2617. [European Peptide Symposium /29./. 03.09.2006-08.09.2006, Gdansk] Institutional research plan: CEZ:AV0Z40550506 Keywords : CART peptides * food intake * mouse obesity * CCK Subject RIV: CC - Organic Chemistry

  16. Structure-activity relationship of cocaine- and amphetamine-regulated transcript (CART) by peptide analogs: Importance of disulfide bridges

    Czech Academy of Sciences Publication Activity Database

    Blechová, Miroslava; Nagelová, Veronika; Demianova, Zuzana; Železná, Blanka; Maletínská, Lenka

    2012-01-01

    Roč. 18, S1 (2012), S89-S90 ISSN 1075-2617. [European Peptide Symposium /32./. 02.09.2012-07.09.2012, Athens] Institutional research plan: CEZ:AV0Z40550506 Keywords : CART * neuropeptides * cell line PC12 * anorexigenic effect Subject RIV: CE - Biochemistry

  17. Determination of amphetamine, methamphetamine, MDA and MDMA in human hair by GC-EI-MS after derivatization with perfluorooctanoyl chloride

    DEFF Research Database (Denmark)

    Johansen, Sys Stybe; Jornil, Jakob

    2009-01-01

    ), methamphetamine (MA), methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA or ecstasy). An intra-day precision of 3-6% RSD and an inter-day precision of 3-17% RSD were observed. Trueness was between 96 % and 106% for the target compounds. The limit of detection ranged from 0.07 to 0.14 ng...

  18. Corrigendum to "Destruction of amphetamine in aqueous solution using gamma irradiation" [Radiat. Phys. Chem. 139 (2017) 17-21

    Science.gov (United States)

    Alkhuraiji, Turki S.; Ajlouni, Abdul-Wali; Alotaibi, Noura A.

    2018-04-01

    The authors regret to have omitted to add a co-author in the author list of this research article. They would like to add the following author who has contributed to the article: Noura A. Alotaibi, King Fahad Medical City, Riyadh, Saudi Arabia.

  19. Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love").

    Science.gov (United States)

    McNamara, Ruth; Kerans, Aoife; O'Neill, Barry; Harkin, Andrew

    2006-01-01

    The present study determined the effect of caffeine co-administration on the core body temperature response and long-term serotonin (5-HT) loss induced by methylenedioxymethamphetamine (MDMA; "Ecstasy") and its metabolite methylenedioxyamphetamine (MDA; "Love") to rats. In group-housed animals, caffeine (10 mg/kg) enhanced the acute toxicity of MDMA (15 mg/kg) and MDA (7.5 mg/kg), resulting in an exaggerated hyperthermic response (+2 degrees C for 5 h following MDMA and +1.5 degrees C for 3 h following MDA) when compared to MDMA (+1 degree C for 3 h) and MDA (+1 degree C for 1 h) alone. Co-administration of caffeine with MDMA or MDA was also associated with increased lethality. To reduce the risk of lethality, doses of MDMA and MDA were reduced in further experiments and the animals were housed individually. To examine the effects of repeated administration, animals received MDMA (10 mg/kg) or MDA (5 mg/kg) with or without caffeine (10 mg/kg) twice daily for 4 consecutive days. MDMA and MDA alone induced hypothermia (fall of 1 to 2 degrees C) over the 4 treatment days. Co-administration of caffeine with MDMA or MDA resulted in hyperthermia (increase of up to 2.5 degrees C) following acute administration compared to animals treated with caffeine or MDMA/MDA alone. This hyperthermic response to caffeine and MDMA was not observed with repeated administration, unlike caffeine + MDA, where hyperthermia was obtained over the 4 day treatment period. In addition, 4 weeks after the last treatment, co-administration of caffeine with MDA (but not MDMA) induced a reduction in 5-HT and 5-hydroxyindole acetic acid (5-HIAA) concentrations in frontal cortex (to 61% and 58% of control, respectively), hippocampus (48% and 60%), striatum (79% and 64%) and amygdala (63% and 37%). However, when caffeine (10 mg/kg) and MDMA (2.5 mg/kg) were co-administered four times daily for 2 days to group-housed animals, both hyperthermia and hippocampal 5-HT loss were observed (reduced to 68% of control). Neither MDMA nor MDA alone induced a significant reduction in regional 5-HT or 5-HIAA concentrations following repeated administration. In conclusion, caffeine promotes the acute and long-term toxicity associated with MDMA and MDA. This is a serious drug interaction, which could have important acute and long-term health consequences for recreational drug users.

  20. Mephedrone Does not Damage Dopamine Nerve Endings of the Striatum but Enhances the Neurotoxicity of Methamphetamine, Amphetamine and MDMA

    OpenAIRE

    Angoa-Pérez, Mariana; Kane, Michael J.; Briggs, Denise I.; Francescutti, Dina M.; Sykes, Catherine E.; Shah, Mrudang M.; Thomas, David M.; Kuhn, Donald M.

    2013-01-01

    Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its reuptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamin...

  1. Effects of amphetamine and methylphenidate on attentional performance and impulsivity in the mouse 5-Choice Serial Reaction Time Task

    DEFF Research Database (Denmark)

    Caballero Puntiverio, Maitane; Fitzpatrick, Ciarán Martin; Woldbye, David Paul Drucker

    2017-01-01

    assessed. Saline treatment data determined high- and lowattentive (LA), and high- and low-impulsive (LI) subgroups according to the upper and lower 30th percentiles, respectively. Results: In the LA subgroup accuracy was improved by 0.5 mg/kg AMPH and 2 mg/kg MPH, while no effect was found in the high-attentive......Background: Few studies have investigated the effects of conventional attention deficit-hyperactivity disorder (ADHD) medication in the mouse 5-choice serial reaction time task (5-CSRTT), and rat studies have yielded inconsistent results. Objective: We aimed to examine the effects of acute...... (HA) subgroup. Premature responses were increased by 1 mg/kg AMPH and 0.5 mg/kg MPH for all animals, and by 1 mg/kg AMPH for the LI subgroup. Conclusions: The use of variable stimulus duration, along with the division into high- and LA, and high-and LI subgroups, may improve the sensitivity of the 5...

  2. 75 FR 69088 - Determination That Amphetamine Sulfate, 5 and 10 Milligram Tablets, Was Not Withdrawn From Sale...

    Science.gov (United States)

    2010-11-10

    ... products that have been discontinued from marketing for reasons other than safety or effectiveness. ANDAs... Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and... not withdrawn from sale for reasons of safety or effectiveness. This determination will allow FDA to...

  3. The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Brandt-Christensen, Anne Mette; Andersen, M B; Fink-Jensen, A

    2006-01-01

    Low affinity dopamine (DA) D2 antagonists such as the substituted (S)-3-phenylpiperidine (-)-OSU6162 have been proposed to be putative antipsychotic agents not endowed with extrapyramidal side effects (EPS). In the present study we investigated the effects of (-)-OSU6162 on (-)-apomorphine and d-...

  4. Synergistic effect of CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin on food intake regulation in lean mice

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Maixnerová, Jana; Matyšková, Resha; Haugvicová, Renata; Pirnik, Z.; Kiss, A.; Železná, Blanka

    2008-01-01

    Roč. 9, č. 101 (2008), s. 1-10 ISSN 1471-2202 R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510 Keywords : mice * food intake * CART peptide Subject RIV: CE - Biochemistry Impact factor: 2.850, year: 2008

  5. A case story, involving the use of maltitol, a sugar alcohol, as a cutting agent in amphetamine and cocaine powders

    DEFF Research Database (Denmark)

    Reitzel, Lotte Ask; Holm, Niels Bjerre; Linnet, Kristian

    2016-01-01

    . The work described covers the part of the case involving the department of forensic chemistry, and not the whole police investigation, but everything was done within the frames given by the police. To the best of our knowledge, this is the first report of a disaccharide polyol being used as a cutting agent...

  6. Use, indications and distribution in different countries of the stimulant and hallucinogenic amphetamine derivatives under consideration by WHO.

    Science.gov (United States)

    Keup, W

    1986-06-01

    Information is presented on legal manufacture, distribution, medical uses and in various countries of the stimulants and hallucinogens under consideration by the World Health Organization (WHO). Data are reported from the Substance Abuse Warning System (SAWS) in the F.R.G. and other surveillance systems regarding illicit manufacture, trafficking and abuse of these compounds internationally. In addition, it is pointed out that assessment of the liability of these compounds for abuse must consider not only the substance itself but also its potential metabolic products. These data, collectively, indicate that the substances currently of most concern with respect to abuse are fenetylline and norpseudoephedrine.

  7. SOLID-PHASE EXTRACTION FOLLOWED BY DISPERSIVE LIQUID ...

    African Journals Online (AJOL)

    Preferred Customer

    Due to the widespread abuse of amphetamine, methamphetamine and the ... amphetamine (MDPA), drug testing for amphetamines is routinely done in ... assess amphetamines compounds in human urine samples using gas ... Italy) were prepared in methanol at a concentration of 1 mg mL-1 and stored at –18 ºC; working.

  8. CART (cocaine- and amphetamine-regulated transcript) peptide specific binding sites in PC12 cells have characteristics of CART peptide receptors

    Czech Academy of Sciences Publication Activity Database

    Nagelová, Veronika; Pirnik, Z.; Železná, Blanka; Maletínská, Lenka

    2014-01-01

    Roč. 1547, Feb 14 (2014), s. 16-24 ISSN 0006-8993 R&D Projects: GA ČR GAP303/10/1368 Institutional support: RVO:61388963 Keywords : CART peptide * PC12 cell * differentiation * binding * signaling * c-Jun Subject RIV: CE - Biochemistry Impact factor: 2.843, year: 2014

  9. Risky Decision-Making and Ventral Striatal Dopamine Responses to Amphetamine: A Positron Emission Tomography [11C] Raclopride Study in Healthy Adults

    OpenAIRE

    Oswald, Lynn M.; Wand, Gary S.; Wong, Dean F.; Brown, Clayton H.; Kuwabara, Hiroto; Brašić, James R.

    2015-01-01

    Recent functional magnetic resonance imaging (fMRI) studies have provided compelling evidence that corticolimbic brain regions are integrally involved in human decision-making. Although much less is known about molecular mechanisms, there is growing evidence that the mesolimbic dopamine (DA) neurotransmitter system may be an important neural substrate. Thus far, direct examination of DA signaling in human risk-taking has centered onl gambling disorder. Findings from several positron emission ...

  10. Differences between the release of radiolabelled and endogenous dopamine from superfused rat brain slices: effects of depolarizing stimuli, amphetamine and synthesis inhibition

    International Nuclear Information System (INIS)

    Herdon, H.; Strupish, J.; Nahorski, S.R.

    1985-01-01

    Direct comparisons between radiolabelled and endogenous dopamine (DA) release from superfused rat brain slices have been made. Striatal slices were prelabelled with [ 3 H]dopamine ([ 3 H]DA), then superfused at 0.5 ml/min and the released catecholamines analyzed by HPLC with electrochemical detection and radioactivity present in superfusate fractions also counted. The studies indicate that labelled and endogenous amine release do not always occur in parallel, and that major causes of discrepancy between them may include the presence of a large newly-synthesized component in endogenous release and the uneven distribution of labelled amine within endogenous releasable pools. The results also suggest that the prelabelling process itself may alter the pools contributing to subsequent endogenous release. (Auth.)

  11. Radioenzymatic paper-chromatographic assay for dopamine and norepinephrine in cerebroventricular cisternal perfusate of cat following administration of cocaine or d-amphetamine

    Energy Technology Data Exchange (ETDEWEB)

    Chiueh, C C; Kopin, I J [National Inst. of Mental Health, Bethesda, MD (USA)

    1978-08-01

    A sensitive radioenzymatic paper chromatographic method was used to measure the endogenous dopamine and norepinephrine content of cerebroventricular cisternal perfusate from cats to provide direct evidence for the catecholamine releasing action of cocaine from brain in vivo. Although relatively less potent than d-emphetamine, cocaine was shown to release endogenous catechloramines, mainly dopamine from the brain. This similarity may be the neurochemical basis for their similar behavioral effects.

  12. Electrochemical and spectroscopic characterisation of amphetamine-like drugs: Application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors

    International Nuclear Information System (INIS)

    Milhazes, Nuno; Martins, Pedro; Uriarte, Eugenio; Garrido, Jorge; Calheiros, Rita; Marques, M. Paula M.; Borges, Fernanda

    2007-01-01

    A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-β-methyl-β-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to the formation of a primary amine and an aldehyde. The vibrational spectroscopic experiments enable to afford a rapid and reliable detection of this type of compounds, since they yield characteristic spectral patterns that lead to an unequivocal identification. Moreover, the rational synthesis of the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') from one of its most relevant precursors 3,4-methylene-dioxyamphetamine (MDA), is reported. In addition, several approaches for the N-methylation of MDA, a limiting synthetic step, were attempted and the overall yields compared

  13. Electrochemical and spectroscopic characterisation of amphetamine-like drugs: Application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors

    Energy Technology Data Exchange (ETDEWEB)

    Milhazes, Nuno [CEQOFFUP, Faculdade de Farmacia, Universidade do Porto (Portugal); Departamento de Quimica Organica, Faculdade de Farmacia, Universidade do Porto (Portugal); Instituto Superior de Ciencias da Saude-Norte, Gandra, Paredes (Portugal); Martins, Pedro [Departamento de Quimica Organica, Facultade de Farmacia, Universidad de Santiago de Compostela (Spain); Uriarte, Eugenio [Departamento de Quimica Organica, Facultade de Farmacia, Universidad de Santiago de Compostela (Spain); Garrido, Jorge [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Departamento de Engenharia Quimica, ISEP, Instituto Politecnico do Porto (Portugal); Calheiros, Rita [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Marques, M. Paula M. [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Departamento de Bioquimica, Faculdade de Ciencias e Tecnologia, Universidade de Coimbra (Portugal); Borges, Fernanda [Departamento de Quimica Organica, Faculdade de Farmacia, Universidade do Porto (Portugal) and Unidade I and D ' Quimica-Fisica Molecular' (Portugal)]. E-mail: fborges@ff.up.pt

    2007-07-23

    A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-{beta}-methyl-{beta}-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to the formation of a primary amine and an aldehyde. The vibrational spectroscopic experiments enable to afford a rapid and reliable detection of this type of compounds, since they yield characteristic spectral patterns that lead to an unequivocal identification. Moreover, the rational synthesis of the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') from one of its most relevant precursors 3,4-methylene-dioxyamphetamine (MDA), is reported. In addition, several approaches for the N-methylation of MDA, a limiting synthetic step, were attempted and the overall yields compared.

  14. Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

    DEFF Research Database (Denmark)

    Palner, Mikael; Kjaerby, Celia; Knudsen, Gitte M

    2011-01-01

    It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved...... ligands should likewise be fitter than antagonists for detecting responses to denervation in positron emission tomography studies of idiopathic Parkinson's disease. Agonist binding increases in vivo are likely to reflect the composite of a sensitization-like phenomenon, and relatively less competition...... from endogenous dopamine, as seen in the lesioned side of 6-OHDA induced hemi-parkinsonism....

  15. Anorexigenic effect of cholecystokinin is lost but that of CART (cocaine and amphetamine regulated transcript) peptide is preserved in monosodium glutamate obese mice

    Czech Academy of Sciences Publication Activity Database

    Železná, Blanka; Maixnerová, Jana; Matyšková, Resha; Haugvicová, Renata; Blokešová, Darja; Maletínská, Lenka

    2009-01-01

    Roč. 58, č. 5 (2009), s. 717-723 ISSN 0862-8408 R&D Projects: GA ČR GA303/05/0614 Grant - others:GA ČR(CZ) GA305/06/0427 Program:GA Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z5020903 Keywords : monosodium glutamate (MSG) obesity * neuropeptide Y (NPY) * cholecystokinin Subject RIV: CC - Organic Chemistry Impact factor: 1.430, year: 2009

  16. Determination of amphetamine-type stimulants (ATSs) and synthetic cathinones in urine using solid phase micro-extraction fibre tips and gas chromatography-mass spectrometry

    OpenAIRE

    Alsenedi, Khalid A.; Morrison, Calum

    2018-01-01

    In recent years, an increasing number of stimulant drugs and new psychoactive substances (NPSs) have caused concern in scientific communities and therefore innovative methods to extract compounds from complex biological samples are required. This work is aimed at developing and validating a clean, convenient and straightforward extraction procedure with microliter amounts of organic solvent using Solid Phase Micro-Extraction tips (SPME tips) and analysis using Gas Chromatography-Mass Spectrom...

  17. Effects of (Des-Tyr1)-γ-endorphin and α-endorphin as compared to haloperidol and amphetamine on nucleus accumbens self-stimulation

    NARCIS (Netherlands)

    Ree, J.M. van; Otte, A.P.

    The β-endorphin fragment (Des-Tyr1)-γ-endorphin (DTγE, β-LPH 62–77) attenuated self-stimulation behaviour associated with electrical stimulation of the nucleus accumbens area of rats. This effect was observed after subcutaneous (s.c.) injection of 2.5 and 25 μg of the neuropeptide and appeared to be

  18. Association of cocaine- and amphetamine-related transcript, leptin and leptin receptor gene polymorphisms with anthropometric obesity phenotype indicators in South African learners.

    Science.gov (United States)

    Yako, Y Y; Fanampe, B L; Hassan, M S; Erasmus, R T; van der Merwe, L; van Rensburg, S J; Matsha, T E

    2011-01-01

    Obesity has increased rapidly in South African children and adolescents. Genes involved in appetite regulation have been extensively studied worldwide, but their role in the obesity phenotype in South African Black and mixed-ancestry school adolescents is unknown. Seven common polymorphisms in LEP, GHRL, CART and LEPR were analysed for genotype and haplotype association with anthropometric obesity phenotype indicators in South African Black and mixed-ancestry adolescent school learners. The CART c.517A→G polymorphism was significantly associated with obesity susceptibility. The LEPR Lys(109)Arg G allele was associated with an average reduction of 2.36 kg/m(2) in body mass index (BMI), 5.66 cm in waist circumference (WC) and 1.61 cm in mid-upper-arm circumference (MUAC). This was confirmed by haplotype analysis. Additionally, a haplotype of the LEP polymorphisms significantly increased BMI, MUAC and hip circumference, while LEPR haplotypes were associated with differences in MUAC. Our findings suggest that c.517A→G and Lys(109)Arg contribute to the variation in anthropometric obesity phenotype indicators observed among Black African and mixed-ancestry South African learners. Furthermore, haplotypes of LEP, LEPR and GHRL polymorphisms were associated with varying measurements of weight, BMI and WC. Further studies are required to confirm our results in a larger and homogeneous study population group. Copyright © 2011 S. Karger AG, Basel.

  19. Radioenzymatic paper-chromatographic assay for dopamine and norepinephrine in cerebroventricular cisternal perfusate of cat following administration of cocaine or d-amphetamine

    International Nuclear Information System (INIS)

    Chiueh, C.C.; Kopin, I.J.

    1978-01-01

    A sensitive radioenzymatic paper chromatographic method was used to measure the endogenous dopamine and norepinephrine content of cerebroventricular cisternal perfusate from cats to provide direct evidence for the catecholamine releasing action of cocaine from brain in vivo. Although relatively less potent than d-emphetamine, cocaine was shown to release endogenous catechloramines, mainly dopamine from the brain. This similarity may be the neurochemical basis for their similar behavioral effects. (U.K.)

  20. Electrochemical and spectroscopic characterisation of amphetamine-like drugs: Application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors

    OpenAIRE

    Milhazes, Nuno; Martins, Pedro; Uriarte, Eugenio; Garrido, Jorge; Calheiros, Rita; Marques, M. Paula M.; Borges, Fernanda

    2007-01-01

    A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-beta-methyl-beta-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to t...

  1. Electrochemical and spectroscopic characterisation of amphetamine-like drugs: application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors.

    Science.gov (United States)

    Milhazes, Nuno; Martins, Pedro; Uriarte, Eugenio; Garrido, Jorge; Calheiros, Rita; Marques, M Paula M; Borges, Fernanda

    2007-07-23

    A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-beta-methyl-beta-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to the formation of a primary amine and an aldehyde. The vibrational spectroscopic experiments enable to afford a rapid and reliable detection of this type of compounds, since they yield characteristic spectral patterns that lead to an unequivocal identification. Moreover, the rational synthesis of the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") from one of its most relevant precursors 3,4-methylene-dioxyamphetamine (MDA), is reported. In addition, several approaches for the N-methylation of MDA, a limiting synthetic step, were attempted and the overall yields compared.

  2. Effects of the cannabinoid CB1 receptor agonist CP55,940 and antagonist SR141716A on d-amphetamine-induced behaviours in Cebus monkeys

    DEFF Research Database (Denmark)

    Madsen, Morten V; Peacock, Linda; Werge, Thomas

    2006-01-01

    Several clinical studies have shown that alterations in the cannabinoid system in the brain may be associated with schizophrenia. Although evidence points towards an antipsychotic potential for cannabinoid antagonists, experimental studies have shown inconsistent behavioural effects of cannabinoi...

  3. Genetic targeting of the amphetamine and methylphenidate-sensitive dopamine transporter: On the path to an animal model of attention-deficit hyperactivity disorder

    Science.gov (United States)

    Mergy, Marc A.; Gowrishankar, Raajaram; Davis, Gwynne L.; Jessen, Tammy N.; Wright, Jane; Stanwood, Gregg D.; Hahn, Maureen K.; Blakely, Randy D.

    2014-01-01

    Alterations in dopamine (DA) signaling underlie the most widely held theories of molecular and circuit level perturbations that lead to risk for attention-deficit hyperactivity disorder (ADHD). The DA transporter (DAT), a presynaptic reuptake protein whose activity provides critical support for DA signaling by limiting DA action at pre- and postsynaptic receptors, has been consistently associated with ADHD through pharmacological, behavioral, brain imaging and genetic studies. Currently, the animal models of ADHD exhibit significant limitations, stemming in large part from their lack of construct validity. To remedy this situation, we have pursued the creation of a mouse model derived from a functional nonsynonymous variant in the DAT gene (SLC6A3) of ADHD probands. We trace our path from the identification of these variants to in vitro biochemical and physiological studies to the production of the DAT Val559 mouse model. We discuss our initial findings with these animals and their promise in the context of existing rodent models of ADHD. PMID:24332984

  4. Consumption of anorexigenic amphetamine-like drugs (diethylpropion, fenproporex and mazindol) and of d,1-fenfluramine in Brazil during the years of 1988 and 1989.

    Science.gov (United States)

    Nappo, S A

    1996-01-01

    Brazilian consumption of psychostimulant anorexigenic drugs--diethylpropion, fenproporex, and mazindol--and of 3,1-fenfluramine was studied, and results are presented in terms of DDDs/1000 inhabitants/day. As of 1988, consumption of these drugs in Brazil was equal to 4.59 DDDs/1000 inhabitants/day; in the following year it had risen by 43.8%. However, if only the population that can afford to buy medicines is considered, actual consumption figures are at least three times higher. Such numbers point to a very high rate of anorexigenic consumption in Brazil, in contrast with other countries where use of these drugs is smaller. It was also found that 68.6% of total consumption in 1988--and 39.4% in 1989--corresponded to prescription formulas prepared by specialized pharmacies, while the remainder was consumed in the form of ready-made medicines produced by pharmaceutical industries. The most used drugs were mazindol in 1988, and fenproporex in 1989; d,1-fenfluramine was the least used of these substances in both years. These reasons are discussed for this increased consumption in Brazil and the absence of an adequate controlling attitude on the part of public health authorities.

  5. Cocaine- and amphetamine-regulated transcript promotes the differentiation of mouse bone marrow-derived mesenchymal stem cells into neural cells

    Directory of Open Access Journals (Sweden)

    Jin Jiali

    2011-07-01

    Full Text Available Abstract Background Neural tissue has limited potential to self-renew after neurological damage. Cell therapy using BM-MSCs (bone marrow mesenchymal stromal cells seems like a promising approach for the treatment of neurological diseases. However, the neural differentiation of stem cells influenced by massive factors and interactions is not well studied at present. Results In this work, we isolated and identified MSCs from mouse bone marrow. Co-cultured with CART (0.4 nM for six days, BM-MSCs were differentiated into neuron-like cells by the observation of optical microscopy. Immunofluorescence demonstrated that the differentiated BM-MSCs expressed neural specific markers including MAP-2, Nestin, NeuN and GFAP. In addition, NeuN positive cells could co-localize with TH or ChAT by double-labled immunofluorescence and Nissl bodies were found in several differentiated cells by Nissl stain. Furthermore, BDNF and NGF were increased by CART using RT-PCR. Conclusion This study demonstrated that CART could promote the differentiation of BM-MSCs into neural cells through increasing neurofactors, including BNDF and NGF. Combined application of CART and BM-MSCs may be a promising cell-based therapy for neurological diseases.

  6. Cocaine- and amphetamine-regulated transcript promotes the differentiation of mouse bone marrow-derived mesenchymal stem cells into neural cells

    OpenAIRE

    Jin Jiali; Chen Zhibin; Zhang Meijuan; Huang Danqing; Liu Zhuo; Huang Siyuan; Zhang Zhuo; Wang Zhongyuan; Chen Lei; Chen Ling; Xu Yun

    2011-01-01

    Abstract Background Neural tissue has limited potential to self-renew after neurological damage. Cell therapy using BM-MSCs (bone marrow mesenchymal stromal cells) seems like a promising approach for the treatment of neurological diseases. However, the neural differentiation of stem cells influenced by massive factors and interactions is not well studied at present. Results In this work, we isolated and identified MSCs from mouse bone marrow. Co-cultured with CART (0.4 nM) for six days, BM-MS...

  7. Cocaine and amphetamine-regulated transcript (CART) concentration in maternal and cord blood in type 1 diabetic and non diabetic pregnancies at term

    LENUS (Irish Health Repository)

    Hehir, MP

    2011-02-01

    Institute of Obstetricians & Gynaecologists, RCPI Four Provinces Meeting, Junior Obstetrics & Gynaecology Society Annual Scientific Meeting, Royal Academy of Medicine in Ireland Dublin Maternity Hospitals Reports Meeting Nov 2010

  8. Orexinergic innervation of urocortin1 and cocaine and amphetamine regulated transcript neurons in the midbrain centrally projecting Edinger-Westphal nucleus.

    NARCIS (Netherlands)

    Emmerzaal, T.L.; Doelen, R.H.A. van der; Roubos, E.W.; Kozicz, L.T.

    2013-01-01

    Orexin is a neuropeptide that has been implicated in several processes, such as induction of appetite, arousal and alertness and sleep/wake regulation. Multiple lines of evidence also suggest that orexin is involved in the stress response. When orexin is administered intracerebroventricular it

  9. 75 FR 55828 - Controlled Substances: Final Revised Aggregate Production Quotas for 2010

    Science.gov (United States)

    2010-09-14

    ..., amphetamine (for conversion), amphetamine (for sale), carfentanil, dihydromorphine, diphenoxylate, marihuana... Lysergic acid diethylamide (LSD) 15 g Marihuana 21,000 g Mescaline 5 g Methaqualone 7 g Methcathinone 4 g...

  10. Methamphetamine overdose

    Science.gov (United States)

    ... dialysis (kidney machine) Destruction of muscles, which can lead to amputation An extremely large methamphetamine overdose can cause death. Alternative Names Intoxication - amphetamines; Intoxication - uppers; Amphetamine intoxication; Uppers overdose; Overdose - ...

  11. Effect of traditional medicine brahmi vati and bacoside A-rich fraction of Bacopa monnieri on acute pentylenetetrzole-induced seizures, amphetamine-induced model of schizophrenia, and scopolamine-induced memory loss in laboratory animals.

    Science.gov (United States)

    Mishra, Amrita; Mishra, Arun K; Jha, Shivesh

    2018-03-01

    Brahmi vati (BV) is an Ayurvedic polyherbal formulation used since ancient times and has been prescribed in seizures associated with schizophrenia and related memory loss by Ayurvedic practitioners in India. The aim of the study was to investigate these claims by evaluation of anticonvulsant, antischizophreniac, and memory-enhancing activities. Antioxidant condition of brain was determined by malondialdehyde (MDA) and reduced glutathione (GSH) levels estimations. Acetylcholinesterase (AChE) was quantitatively estimated in the brain tissue. Brahmi vati was prepared in-house by strictly following the traditional Ayurvedic formula. Bacoside A rich fraction (BA) of Bacopa monnieri was prepared by extraction and fractionation. It was than standardized by High Performance Liquid Chromatography (HPLC) and given in the dose of 32.5mg/kg body weight to the different groups of animals for 7days. On the seventh day, activities were performed adopting standard procedures. Brahmi vati showed significant anticonvulsant, memory-enhancing and antischizophrenia activities, when compared with the control groups and BA. It cause significantly higher brain glutathione levels. Acetylcholinesterase activity was found to be significantly low in BV-treated group. The finding of the present study suggests that BV may be used to treat seizures associated with schizophrenia and related memory loss. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Effect of anorexinergic peptides, cholecystokinin (CCK) and cocaine and amphetamine regulated transcript (CART) peptide, on the activity of neurons in hypothalamic structures of C57Bl/6 mice involved in the food intake regulation

    Czech Academy of Sciences Publication Activity Database

    Pirnik, Z.; Maixnerová, Jana; Matyšková, Resha; Koutová, Darja; Železná, Blanka; Maletínská, Lenka; Kiss, A.

    2010-01-01

    Roč. 31, č. 1 (2010), s. 139-144 ISSN 0196-9781 R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506 Keywords : cholecystokinin * CART * hypocretin * Fos peptide Subject RIV: CE - Biochemistry Impact factor: 2.654, year: 2010

  13. 77 FR 47114 - Manufacturer of Controlled Substances; Notice of Application; AMRI Rensselaer, Inc.

    Science.gov (United States)

    2012-08-07

    ... Marihuana (7360) I Tetrahydrocannabinols (7370) I Amphetamine (1100) II Lisdexamfetamine (1205) II... (Marihuana), the company plans to bulk manufacture cannabidiol as a synthetic intermediate, which will be...

  14. Intracellular Methamphetamine Prevents the Dopamine-induced Enhancement of Neuronal Firing*

    Science.gov (United States)

    Saha, Kaustuv; Sambo, Danielle; Richardson, Ben D.; Lin, Landon M.; Butler, Brittany; Villarroel, Laura; Khoshbouei, Habibeh

    2014-01-01

    The dysregulation of the dopaminergic system is implicated in multiple neurological and neuropsychiatric disorders such as Parkinson disease and drug addiction. The primary target of psychostimulants such as amphetamine and methamphetamine is the dopamine transporter (DAT), the major regulator of extracellular dopamine levels in the brain. However, the behavioral and neurophysiological correlates of methamphetamine and amphetamine administration are unique from one another, thereby suggesting these two compounds impact dopaminergic neurotransmission differentially. We further examined the unique mechanisms by which amphetamine and methamphetamine regulate DAT function and dopamine neurotransmission; in the present study we examined the impact of extracellular and intracellular amphetamine and methamphetamine on the spontaneous firing of cultured midbrain dopaminergic neurons and isolated DAT-mediated current. In dopaminergic neurons the spontaneous firing rate was enhanced by extracellular application of amphetamine > dopamine > methamphetamine and was DAT-dependent. Amphetamine > methamphetamine similarly enhanced DAT-mediated inward current, which was sensitive to isosmotic substitution of Na+ or Cl− ion. Although isosmotic substitution of extracellular Na+ ions blocked amphetamine and methamphetamine-induced DAT-mediated inward current similarly, the removal of extracellular Cl− ions preferentially blocked amphetamine-induced inward current. The intracellular application of methamphetamine, but not amphetamine, prevented the dopamine-induced increase in the spontaneous firing of dopaminergic neurons and the corresponding DAT-mediated inward current. The results reveal a new mechanism for methamphetamine-induced dysregulation of dopaminergic neurons. PMID:24962577

  15. 76 FR 65371 - Schedules of Controlled Substances: Temporary Placement of Three Synthetic Cathinones Into...

    Science.gov (United States)

    2011-10-21

    ... amphetamine, cathinone, methcathinone, and methamphetamine, are central nervous system (CNS) stimulants. The..., palpitations, muscular tension in the jaw and limbs, headache, agitation, anxiety, tremor, and fever or...

  16. 76 FR 40306 - Harmonizing Schedule I Drug Requirements

    Science.gov (United States)

    2011-07-08

    ... an amphetamine, narcotic, or any habit-forming drug, are not medically qualified to operate a... of the 1984 Act also grants the Secretary broad power in carrying out motor carrier safety statutes...: Controlled substances on the DEA Schedule I, amphetamines, narcotics, or other habit-forming drugs. Section...

  17. Some remarks on the effects of drugs, lack of sleep and loud noise on human performance.

    NARCIS (Netherlands)

    Sanders, A.F. & A.A. Bunt.

    1971-01-01

    Some literature is reviewed on the effect of some drugs, (amphetamine, hypnotics, alcohol), loud noise and sleep loss in test of time estimation, decision making, long term performance and short term memory. Results are most clear with respect to amphetamine, hypnotics and lack of sleep, in that

  18. Review: Methamphetamine use by pregnant women: Impact on the ...

    African Journals Online (AJOL)

    According to the United Nations Office on Drugs and Crime (UNODC)'s 2011 World Drug Report, amphetamine-type stimulants (ATS) are the second most widely used illicit drug group. This drug group comprises methamphetamine, amphetamine and ecstasy. Methamphetamine is the most widely manufactured drug in this ...

  19. Psychoactive substances in seriously injured drivers in Denmark

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Steentoft, Anni; Bernhoft, Inger Marie

    2013-01-01

    at levels above LOQ, whereas amphetamines (5.4%) (amphetamine [5.2%] and methamphet-amine [1.5%]), tetrahydrocannabinol (3.7%), and cocaine (3.3%), including the metabolite benzoylecgo-nine, were the most frequently detected illegal drugs. A driver could be positive for more than one substance; therefore...

  20. Discrimination Between Drug Abuse and Medical Therapy: Case report of a tranylcypromine overdose-related fatality

    Directory of Open Access Journals (Sweden)

    Maryam Akhgari

    2017-06-01

    Full Text Available Tranylcypromine is an effective antidepressant from the class of monoamine oxidase inhibitors and is structurally related to amphetamine. However, reports differ regarding the potential metabolism of tranylcypromine to amphetamine and methamphetamine within the human body. We report a 25-year-old woman with severe depression who died due to a fatal tranylcypromine overdose in 2016. She had been prescribed tranylcypromine one day previously and had no history of previous suicide attempts or substance abuse. The body was transferred to a forensic medicine department in Tehran, Iran for the autopsy. A urine sample was positive for tranylcypromine, amphetamine and methamphetamine using gas chromatography/mass spectrometry after derivatisation with heptafluorobutyric acid. As amphetamines were present in the urine sample, it was assumed that the tranylcypromine had been converted to amphetamines metabolically. As such, it is possible that the legitimate use of certain prescription drugs may complicate the interpretation of test results for illegal drugs.

  1. Fenetylline: new results on pharmacology, metabolism and kinetics.

    Science.gov (United States)

    Nickel, B; Niebch, G; Peter, G; von Schlichtegroll, A; Tibes, U

    1986-06-01

    In the fenetylline molecule, theophylline is covalently linked with amphetamine via an alkyl chain. The inclusion of amphetamine and results from early metabolic studies have led to speculation that fenetylline may be merely a prodrug for amphetamine and/or theophylline. Although previous studies are not consistent with this hypothesis, additional studies were conducted to comparatively evaluate the profiles of activity exhibited by fenetylline and its two postulated primary metabolites, (+/-)-amphetamine and theophylline. Investigations were also initiated using newly developed high pressure liquid chromatography (HPLC) techniques to further characterize the metabolic pattern that fenetylline undergoes and to examine the relationship between plasma pharmacokinetics and the pharmacodynamic actions of the drug. Fenetylline inhibits activity associated with amphetamine in certain test systems, an effect similar to that previously observed with fenfluramine. Only small amounts of the amphetamine theoretically available in the fenetylline molecule are released. Pharmacodynamic activity associated with fenetylline administration is more closely tied to plasma levels of the parent compound than to any (+/-)-amphetamine produced.

  2. Ethanol induces rotational behavior in 6-hydroxydopamine lesioned mice

    Energy Technology Data Exchange (ETDEWEB)

    Silverman, P.B.

    1987-03-09

    Mice with unilateal striatal lesions created by 6-hydroxydopamine (6HDA) injection were screened for rotational (circling) behavior in response to injection of amphetamine and apomorphine. Those that rotated ipsilaterally in response to amphetamine and contralaterally in response to apomorphine were subsequently challenged with 1 to 3 g/kg (i.p.) ethanol. Surprisingly, ethanol induced dose related contralateral (apomorphine-like) rotation which, despite gross intoxication, was quite marked in most animals. No significant correlation was found between the number of turns made following ethanol and made after apomorphine or amphetamine. 14 references, 2 figures, 1 table.

  3. Separation of [Rh-103m]-rhodocene-derivatives from the parent [103Ru]ruthenocen-derivatives and their organ distribution

    International Nuclear Information System (INIS)

    Wenzel, M.; Wu, Y.

    1987-01-01

    The radioactive decay of [ 103 Ru]ruthenocene derivatives leads to sup(103m)Rh labelled rhodocinium derivatives, which can be separated by the extraction of a lipophilic solution of the ruthenocen derivate with water. The separation factor sup(103m)Rh/ 103 Ru reaches values of 32:1 Rh 3+ ions are not liberated and extracted. The organ distribution of the sup(103m)Rh labelled rhodocinium derivatives gained from ruthenocene and from N-isopropyl-ruthenocene amphetamine is different from the distribution of the parent ruthenocene compound. The liver and kidney uptake of the rhodocinium-amphetamine is much higher than the uptake with ruthenocene amphetamine. (author)

  4. 49 CFR 391.41 - Physical qualifications for drivers.

    Science.gov (United States)

    2010-10-01

    ... impairment of: (i) A hand or finger which interferes with prehension or power grasping; or (ii) An arm, foot... amphetamine, a narcotic, or any other habit-forming drug. (ii) Exception. A driver may use such a substance or...

  5. Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research

    NARCIS (Netherlands)

    Crunelle, C.L.; Veltman, D.J.; Booij, J.; van Emmerik-van Oortmerssen, K.; van den Brink, W.

    2012-01-01

    Stimulant dependence is associated with neuropsychological impairments. Here, we summarize and integrate the existing neuroimaging literature on the neural substrates of neuropsychological (dys)function in stimulant dependence, including cocaine, (meth-)amphetamine, ecstasy and nicotine dependence,

  6. Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research

    NARCIS (Netherlands)

    Crunelle, Cleo L.; Veltman, Dick J.; Booij, Jan; Emmerik-van Oortmerssen, Katelijne; den Brink, Wim

    2012-01-01

    Stimulant dependence is associated with neuropsychological impairments. Here, we summarize and integrate the existing neuroimaging literature on the neural substrates of neuropsychological (dys) function in stimulant dependence, including cocaine, (meth-) amphetamine, ecstasy and nicotine

  7. Disease: H01730 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available emand of heart. Cardiovascular disease ... Old age Tobacco smoking High blood pressure High levels of LDL High cholesterol and fat Diab...etes Obesity Chronic kidney disease Alcohol Cocaine Amphetamines ... Cardiac troponin

  8. ORIGINAL ARTICLES

    African Journals Online (AJOL)

    monoclonal amphetamine-assay result of antipsychotic drug therapy. Clin Chern 1993; 39: .... reported by the family at accessible clinic or mobile points. A history and .... service delivery; (ii) disability prevention must be a high priority because ...

  9. Effect of autonomic blocking agents and structurally related substances on the “salt arousal of drinking”

    NARCIS (Netherlands)

    Wied, D. de

    The effect of autonomic blocking agents and structurally related substances was studied in rats in which thirst was produced by the administration of a hypertonic sodium chloride solution. Scopolamine, methamphetamine, amphetamine, chlorpromazine, atropine, mecamylamine, hexamethonium, nethalide,

  10. Spontaneous pneumomediastinum: A rare complication of methamphetamine use

    Directory of Open Access Journals (Sweden)

    Jessica Albanese

    2017-01-01

    Conclusion: Spontaneous pneumomediastinum is a rare complication of amphetamine use that is often associated with subcutaneous emphysema and can be diagnosed with chest x-ray. Management is conservative, with observation, pain control, and supplemental oxygen as needed.

  11. Rekreacyjne używanie leków dostępnych w odręcznej sprzedaży: odurzanie i doping mózgu

    Directory of Open Access Journals (Sweden)

    Aleksandra Piątek

    2015-03-01

    Pseudoephedrine, an amphetamine-like stimulant, produces mood improvement or even euphoria, hallucinations and psychosis. However, the real health threat is associated with the use of substances produced from pseudoephedrine: ephedrone and methamphetamine.

  12. Download this PDF file

    African Journals Online (AJOL)

    Administrator

    Keywords: Solanum nigrum;anti-seizure activity; chicks; mice; rats ... from minimal impairment of the central nervous system .... At higher doses, seizure activity was abolished completely. Amphetamine potentiated the anticonvulsant activity of.

  13. Browse Title Index

    African Journals Online (AJOL)

    Items 751 - 800 of 1007 ... ... chromium from aqueous solution using activated carbon derived .... Vol 26, No 1 (2012), Solid phase extraction of trace amounts of ... of ecstasy compounds and amphetamines in biological samples, Abstract PDF.

  14. Evaluation of Short-Term Bioassays to Predict Functional Impairment, Development of Neurobehavioral Bioassays in Laboratory Animals, Directory of Institutions/Individuals.

    Science.gov (United States)

    1980-10-01

    SPONTANEOUS MOTOR ACTIVITY (PHOTOCELL, OPEN FIELD) TEST SYSTEMS UTILIZED: RATS, DOGS, MONKEYS COMPOUNDS TESTED: ABUSE DRUGS - CANNABIS , COCAINE METABOLITES...TEST SYSTEMS UTILIZED: RATS, DOGS, PIGS COMPOUNDS TESTED: GRAS COMPOUNDS FOOD ADDITIVES CNS STIMULANTS: AMPHETAMINE CAFFEINE MYCOTOXINS ACRYLAMIIE

  15. The Prevalence and Factors affecting Psychoactive Substance Use ...

    African Journals Online (AJOL)

    UNIBEN

    Background: Psychoactive substance use is a proliferating public health and social problem leading to negative ... cannabis and 12.2% for cigarettes.8 In Nigeria, the most common ... and amphetamines such as caffeine, tobacco, nicotine ...

  16. Bibliography [On Drugs].

    Science.gov (United States)

    National Association of Student Personnel Administrators, Detroit, MI.

    A bibliography of materials on drugs is presented. The book and paper back entries are annotated. Selected technical references are listed under these major findings: (1) dependency, (2) barbiturates, (3) amphetamines, and (4) general pharmacology. (PS)

  17. 77 FR 55500 - Controlled Substances: Final Adjusted Aggregate Production Quotas for 2012

    Science.gov (United States)

    2012-09-10

    ... (for conversion), amphetamine (for sale), codeine (for conversion), codeine (for sale), desomorphine...), desomorphine, diethyltryptamine, dihydromorphine, gamma hydroxybutyric acid, hydrocodone (for sale... g Codeine-N-oxide 602 g Desomorphine 10 g Diethyltryptamine 18 g Difenoxin 50 g Dihydromorphine 3...

  18. Recent applications of mass spectrometry in forensic toxicology

    Science.gov (United States)

    Foltz, Rodger L.

    1992-09-01

    This review encompasses applications of mass spectrometry reported during the years 1989, 1990 and 1991 for the analysis of cannabinoids, cocaine, opiates, amphetamines, lysergic acid diethylamide (LSD), and their metabolites in physiological specimens.

  19. Application of Sweat Patch Screening for 16 Drugs and Metabolites Using a Fast and Highly Selective LC-MS/MS Method

    NARCIS (Netherlands)

    Koster, Remco A.; Alffenaar, Jan-Willem C.; Greijdanus, Ben; VanDerNagel, Joanneke E. L.; Uges, Donald R. A.

    Background: To facilitate the monitoring of drug abuse by patients, a method was developed and validated for fast and highly selective screening for amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylphenidate, cocaine,

  20. 41 CFR Appendix to Part 102 - 74-Rules and Regulations Governing Conduct on Federal Property

    Science.gov (United States)

    2010-07-01

    ... from— (a) Being under the influence, using or possessing any narcotic drugs, hallucinogens, marijuana... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines. Alcoholic... the GSA Regional Administrator, which will have the same force and effect as these regulations; (e...

  1. 75 FR 49955 - Hung Thien Ly, M.D.; Revocation of Registration

    Science.gov (United States)

    2010-08-16

    ... substance; and amphetamine sulfate, a schedule II controlled substance. For his crimes, the District Court.... Moreover, in the event that Respondent's confidence in the merits of his appeal is borne out, he can apply...

  2. Fast and Highly Selective LC-MS/MS Screening for THC and 16 Other Abused Drugs and Metabolites in Human Hair to Monitor Patients for Drug Abuse

    NARCIS (Netherlands)

    Koster, Remco A.; Alffenaar, Jan-Willem C.; Greijdanus, Ben; VanDerNagel, Joanneke E. L.; Uges, Donald R. A.

    Background:To facilitate the monitoring of drug abuse by patients, a method was developed and validated for the analysis of amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylphenidate, cocaine, benzoylecgonine, morphine,

  3. Central nervous system stimulants and drugs that suppress appetite

    DEFF Research Database (Denmark)

    Aagaard, Lise

    2014-01-01

    of the January 2012 to June 2013 publications on central nervous system stimulants and drugs that suppress appetite covers amphetamines (including metamfetamine, paramethoxyamfetamine and paramethoxymetamfetamine), fenfluramine and benfluorex, atomoxetine, methylphenidate, modafinil and armodafinil...

  4. 10 CFR 710.8 - Criteria.

    Science.gov (United States)

    2010-01-01

    ... marijuana, cocaine, amphetamines, barbiturates, narcotics, etc.) except as prescribed or administered by a physician licensed to dispense drugs in the practice of medicine, or as otherwise authorized by Federal law...

  5. [Detection and identification of a new metabolite of fenethylline].

    Science.gov (United States)

    Goenechea, S; Brzezinka, H

    1984-01-01

    Fenetylline is metabolized in humans on two pathways. In addition to previously described degradation to amphetamine and 7-oxyethyltheophylline fenetylline undergoes moreover oxydative N-dealkylation to yield 7-aminoethyltheophylline and phenylacetone.

  6. Sex differences in methamphetamine pharmacokinetics in adult rats and its transfer to pups through the placental membrane and breast milk

    Czech Academy of Sciences Publication Activity Database

    Rambousek, Lukáš; Kačer, P.; Syslová, K.; Bumba, J.; Bubeníková-Valešová, V.; Šlamberová, R.

    2014-01-01

    Roč. 139, JUN (2014), s. 138-144 ISSN 0376-8716 Institutional support: RVO:67985823 Keywords : methamphetamine * amphetamine * pharmacokinetics * sex differences * breast feeding milk * mass spectrometry Subject RIV: FH - Neurology Impact factor: 3.423, year: 2014

  7. composition_book without cover.indd

    African Journals Online (AJOL)

    central and peripheral effects closely resembles amphetamine (Kalix .... He then continued working with his sister and employee as if ... avoided sleeping at night and restricted his rest hours to the time of the change of shift at the local police.

  8. Semiautomated radioimmunoassay for mass screening of drugs of abuse

    International Nuclear Information System (INIS)

    Sulkowski, T.S.; Lathrop, G.D.; Merritt, J.H.; Landez, J.H.; Noe, E.R.

    1975-01-01

    A rapid, semiautomated radioimmunoassay system for detection of morphine, barbiturates, and amphetamines is described. The assays are applicable to large drug abuse screening programs. The heart of the system is the automatic pipetting station which can accomplish 600 pipetting operations per hour. The method uses 15 to 30 μl for the amphetamine and combined morphine/barbiturate assays. A number of other drugs were tested for interference with the assays and the results are discussed

  9. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    OpenAIRE

    Lozano-Cuenca, J.; González-Hernández, A.; López-Canales, O.A.; Villagrana-Zesati, J.R.; Rodríguez-Choreão, J.D.; Morín-Zaragoza, R.; Castillo-Henkel, E.F.; López-Canales, J.S.

    2017-01-01

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10?9?10?5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-...

  10. The development and applications of polyclonal and monoclonal antibodies for the detection of illicit drugs in saliva samples

    OpenAIRE

    Fanning, Lorna M.

    2002-01-01

    Anti-tetrahydrocannabinol (THC), anti-cocaine and anti-morphine polyclonal antibodies were produced. These antibodies were successfully applied to an ELISA format for the detection of THC, cocaine, and morphine in saliva samples. Monoclonal antibodies against amphetamine and its derivatives were produced using two different conjugates, amphetamine-bovine serum albumin and methamphetaminebovine serum albumin. Two successful clones were produced, and the antibodies were applied to an ELISA ...

  11. Smoking and Soldier Performance: A Literature Review.

    Science.gov (United States)

    1986-06-01

    smokers to be heavy users of coffee , . ., amphetamines, and tranquilizers although no comparison was made AIN with nonsmokers. Prendergast, Preble, and...Oreland (1985) studied 18-yr-olds in Sweden and found regular smokers were more prone to the abuse of alcohol, glue, cannabis , amphetamines, and morphine...laboratory and ’ found smokers took significantly longer to get to sleep than.-.--- nonsmokers (43.7 min versus 29.8 min). Although coffee ’ 7

  12. Evaluation of Na+, K+-ATPase activity in the brain of young rats after acute administration of fenproporex

    OpenAIRE

    Rezin, Gislaine T.; Scaini, Giselli; Gonçalves, Cinara L.; Ferreira, Gabriela K.; Cardoso, Mariane R.; Ferreira, Andréa G.K.; Cunha, Maira J.; Schmitz, Felipe; Varela, Roger B.; Quevedo, João; Wyse, Angela T.S.; Streck, Emilio L.

    2013-01-01

    Objectives: Fenproporex is an amphetamine-based anorectic which is rapidly converted into amphetamine in vivo. Na+, K+-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that the effects of fenproporex on brain metabolism are poorly known and that Na+, K+-ATPase is essential for normal brain function, this study sought to evaluate the effect of this drug on Na+, K+-ATPase activity in the hippocampus, hypothalamus, prefrontal cortex, and striatum of youn...

  13. Imported Fenproporex-based Diet Pills from Brazil: A Report of Two Cases

    OpenAIRE

    Cohen, Pieter A.

    2008-01-01

    Banned amphetamine-based anorectics are illicitly imported into the United States (US), but little is known regarding the harm these diet pills pose to US residents. A 26-year-old woman using imported diet pills presented with a two-year history of intermittent chest pains, palpitations, headaches and insomnia. Urine toxicology screen detected amphetamines and benzodiazepines. Fenproporex and chlordiazepoxide were detected in her pills. Her symptoms resolved after she stopped using diet pills...

  14. Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats

    OpenAIRE

    TEODORAK, BRENA P.; FERREIRA, GABRIELA K.; SCAINI, GISELLI; WESSLER, LETÍCIA B.; HEYLMANN, ALEXANDRA S.; DEROZA, PEDRO; VALVASSORI, SAMIRA S.; ZUGNO, ALEXANDRA I.; QUEVEDO, JOÃO; STRECK, EMILIO L.

    2015-01-01

    Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute...

  15. A gas chromatography-mass spectrometry method for the quantitation of clobenzorex.

    Science.gov (United States)

    Cody, J T; Valtier, S

    1999-01-01

    Drugs metabolized to amphetamine or methamphetamine are potentially significant concerns in the interpretation of amphetamine-positive urine drug-testing results. One of these compounds, clobenzorex, is an anorectic drug that is available in many countries. Clobenzorex (2-chlorobenzylamphetamine) is metabolized to amphetamine by the body and excreted in the urine. Following administration, the parent compound was detectable for a shorter time than the metabolite amphetamine, which could be detected for days. Because of the potential complication posed to the interpretation of amphetamin-positive drug tests following administration of this drug, the viability of a current amphetamine procedure using liquid-liquid extraction and conversion to the heptafluorobutyryl derivative followed by gas chromatography-mass spectrometry (GC-MS) analysis was evaluated for identification and quantitation of clobenzorex. Qualitative identification of the drug was relatively straightforward. Quantitative analysis proved to be a far more challenging process. Several compounds were evaluated for use as the internal standard in this method, including methamphetamine-d11, fenfluramine, benzphetamine, and diphenylamine. Results using these compounds proved to be less than satisfactory because of poor reproducibility of the quantitative values. Because of its similar chromatographic properties to the parent drug, the compound 3-chlorobenzylamphetamine (3-Cl-clobenzorex) was evaluated in this study as the internal standard for the quantitation of clobenzorex. Precision studies showed 3-Cl-clobenzorex to produce accurate and reliable quantitative results (within-run relative standard deviations [RSDs] clobenzorex.

  16. Lisdexamfetamine: chemistry, pharmacodynamics, pharmacokinetics, and clinical efficacy, safety, and tolerability in the treatment of binge eating disorder.

    Science.gov (United States)

    Ward, Kristen; Citrome, Leslie

    2018-02-01

    The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing. D-amphetamine acts primarily to increase the concentrations of synaptic dopamine and norepinephrine. Metabolism of LDX to d-amphetamine occurs when peptidases in red blood cells cleave the covalent bond between d-amphetamine and l-lysine. D-amphetamine is then further metabolized by CYP2D6. Excretion is primarily through renal mechanisms. In clinical trials, LDX demonstrated statistical and clinical superiority over placebo in reducing binge eating days per week at doses of 50 and 70 mg daily. Commonly reported side effects of LDX include dry mouth, insomnia, weight loss, and headache, and its use should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia or coronary artery disease. As with all CNS stimulants, risk of abuse needs to be assessed prior to prescribing.

  17. Cross-generational effects on gender differences in psychoactive drug abuse and dependence.

    Science.gov (United States)

    Holdcraft, Laura C; Iacono, William G

    2004-05-10

    Studies of patients with cocaine and heroin use disorders have shown gender differences in prevalence, course, and outcome. These differences may be decreasing in successive generations. Less is known about gender differences in course and symptomatology for other illicit drug use disorders, especially in community samples. Participants (1323 men and 1384 women) who were biological or step-parents of twins and born in the 1940-1960s, from the Minnesota Twin-Family Study (MTFS) were divided into two cohorts based on the median birth year. A structured interview was used to assess DSM-III-R cannabis, amphetamine, cocaine and hallucinogen use disorders. There was a higher prevalence of each of these drug disorders and earlier onset of cannabis and amphetamine use disorders in later-born participants. For most drug use disorder categories, men and women were similar with respect to age of onset and severity of disorder but women had a shorter course of drug use disorders. Women with amphetamine disorders were atypical with respect to having a higher frequency of use but similar number of lifetime uses compared to men, and more emotional effects of amphetamine intoxication than men. In addition, women with amphetamine disorders were more likely to have anorexia nervosa than those without amphetamine disorders. These results have several implications for prevention, etiology and treatment.

  18. Catecholaminergic consolidation of motor cortical neuroplasticity in humans.

    Science.gov (United States)

    Nitsche, Michael A; Grundey, Jessica; Liebetanz, David; Lang, Nicolas; Tergau, Frithjof; Paulus, Walter

    2004-11-01

    Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.

  19. Psychostimulant Effect of the Synthetic Cannabinoid JWH-018 and AKB48: Behavioral, Neurochemical, and Dopamine Transporter Scan Imaging Studies in Mice.

    Science.gov (United States)

    Ossato, Andrea; Uccelli, Licia; Bilel, Sabrine; Canazza, Isabella; Di Domenico, Giovanni; Pasquali, Micol; Pupillo, Gaia; De Luca, Maria Antonietta; Boschi, Alessandra; Vincenzi, Fabrizio; Rimondo, Claudia; Beggiato, Sarah; Ferraro, Luca; Varani, Katia; Borea, Pier Andrea; Serpelloni, Giovanni; De-Giorgio, Fabio; Marti, Matteo

    2017-01-01

    JWH-018 and AKB48 are two synthetic cannabinoids (SCBs) belonging to different structural classes and illegally marketed as incense, herbal preparations, or chemical supply for theirs psychoactive cannabis-like effects. Clinical reports from emergency room reported psychomotor agitation as one of the most frequent effects in people assuming SCBs. This study aimed to investigate the psychostimulant properties of JWH-018 and AKB48 in male CD-1 mice and to compare their behavioral and biochemical effects with those caused by cocaine and amphetamine. In vivo studies showed that JWH-018 and AKB48, as cocaine and amphetamine, facilitated spontaneous locomotion in mice. These effects were prevented by CB 1 receptor blockade and dopamine (DA) D 1/5 and D 2/3 receptors inhibition. SPECT-CT studies on dopamine transporter (DAT) revealed that, as cocaine and amphetamine, JWH-018 and AKB48 decreased the [ 123 I]-FP-CIT binding in the mouse striatum. Conversely, in vitro competition binding studies revealed that, unlike cocaine and amphetamine, JWH-018 and AKB48 did not bind to mouse or human DAT. Moreover, microdialysis studies showed that the systemic administration of JWH-018, AKB48, cocaine, and amphetamine stimulated DA release in the nucleus accumbens (NAc) shell of freely moving mice. Finally, unlike amphetamine and cocaine, JWH-018 and AKB48 did not induce any changes on spontaneous [ 3 H]-DA efflux from murine striatal synaptosomes. The present results suggest that SCBs facilitate striatal DA release possibly with different mechanisms than cocaine and amphetamine. Furthermore, they demonstrate, for the first time, that JWH-018 and AKB48 induce a psychostimulant effect in mice possibly by increasing NAc DA release. These data, according to clinical reports, outline the potential psychostimulant action of SCBs highlighting their possible danger to human health.

  20. Psychostimulant Effect of the Synthetic Cannabinoid JWH-018 and AKB48: Behavioral, Neurochemical, and Dopamine Transporter Scan Imaging Studies in Mice

    Directory of Open Access Journals (Sweden)

    Andrea Ossato

    2017-08-01

    Full Text Available JWH-018 and AKB48 are two synthetic cannabinoids (SCBs belonging to different structural classes and illegally marketed as incense, herbal preparations, or chemical supply for theirs psychoactive cannabis-like effects. Clinical reports from emergency room reported psychomotor agitation as one of the most frequent effects in people assuming SCBs. This study aimed to investigate the psychostimulant properties of JWH-018 and AKB48 in male CD-1 mice and to compare their behavioral and biochemical effects with those caused by cocaine and amphetamine. In vivo studies showed that JWH-018 and AKB48, as cocaine and amphetamine, facilitated spontaneous locomotion in mice. These effects were prevented by CB1 receptor blockade and dopamine (DA D1/5 and D2/3 receptors inhibition. SPECT-CT studies on dopamine transporter (DAT revealed that, as cocaine and amphetamine, JWH-018 and AKB48 decreased the [123I]-FP-CIT binding in the mouse striatum. Conversely, in vitro competition binding studies revealed that, unlike cocaine and amphetamine, JWH-018 and AKB48 did not bind to mouse or human DAT. Moreover, microdialysis studies showed that the systemic administration of JWH-018, AKB48, cocaine, and amphetamine stimulated DA release in the nucleus accumbens (NAc shell of freely moving mice. Finally, unlike amphetamine and cocaine, JWH-018 and AKB48 did not induce any changes on spontaneous [3H]-DA efflux from murine striatal synaptosomes. The present results suggest that SCBs facilitate striatal DA release possibly with different mechanisms than cocaine and amphetamine. Furthermore, they demonstrate, for the first time, that JWH-018 and AKB48 induce a psychostimulant effect in mice possibly by increasing NAc DA release. These data, according to clinical reports, outline the potential psychostimulant action of SCBs highlighting their possible danger to human health.