WorldWideScience

Sample records for amphetamines

  1. Amphetamine

    Science.gov (United States)

    ... and children. Amphetamine (Evekeo) is used to treat narcolepsy (a sleep disorder that causes excessive daytime sleepiness and sudden attacks ... or without food. For treatment of ADHD or narcolepsy, the immediate-release tablet is usually taken with ...

  2. Amphetamine margin in sports

    Energy Technology Data Exchange (ETDEWEB)

    Laties, V.G.; Weiss, B.

    1981-10-01

    The amphetamines can enhance athletic performance. That much seem clear from the literature, some of which is reviewed here. Increases in endurance have been demonstrated in both humans and rats. Smith and Beecher, 20 years ago, showed improvement of running, swimming, and weight throwing in highly trained athletes. Laboratory analogs of such performances 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.

  3. Toxicity of amphetamines: an update.

    Science.gov (United States)

    Carvalho, Márcia; Carmo, Helena; Costa, Vera Marisa; Capela, João Paulo; Pontes, Helena; Remião, Fernando; Carvalho, Félix; Bastos, Maria de Lourdes

    2012-08-01

    Amphetamines represent a class of psychotropic compounds, widely abused for their stimulant, euphoric, anorectic, and, in some cases, emphathogenic, entactogenic, and hallucinogenic properties. These compounds derive from the β-phenylethylamine core structure and are kinetically and dynamically characterized by easily crossing the blood-brain barrier, to resist brain biotransformation and to release monoamine neurotransmitters from nerve endings. Although amphetamines are widely acknowledged as synthetic drugs, of which amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are well-known examples, humans have used natural amphetamines for several millenniums, through the consumption of amphetamines produced in plants, namely cathinone (khat), obtained from the plant Catha edulis and ephedrine, obtained from various plants in the genus Ephedra. More recently, a wave of new amphetamines has emerged in the market, mainly constituted of cathinone derivatives, including mephedrone, methylone, methedrone, and buthylone, among others. Although intoxications by amphetamines continue to be common causes of emergency department and hospital admissions, it is frequent to find the sophism that amphetamine derivatives, namely those appearing more recently, are relatively safe. However, human intoxications by these drugs are increasingly being reported, with similar patterns compared to those previously seen with classical amphetamines. That is not surprising, considering the similar structures and mechanisms of action among the different amphetamines, conferring similar toxicokinetic and toxicological profiles to these compounds. The aim of the present review is to give an insight into the pharmacokinetics, general mechanisms of biological and toxicological actions, and the main target organs for the toxicity of amphetamines. Although there is still scarce knowledge from novel amphetamines to draw mechanistic insights, the long-studied classical

  4. Analysis of amphetamines illegally produced in Serbia

    OpenAIRE

    VLATKA VAJS; SLOBODAN PETROVIC; SONJA BANOVIC STEVIC; MARINA NEVESCANIN

    2008-01-01

    Forensic practice in the Republic of Serbia faced the illegal production of amphetamine for the first time in 2003. This paper presents the results of the chemical characterization of 32 batches of amphetamine samples from three separate cases, for the purpose of identification of the active components and additives. Through the profiling of impurities of all samples, using gas chromatography/mass spectrometry (GC/MS), 30 compounds associated with amphetamine were identified. The results of t...

  5. Analysis of amphetamines illegally produced in Serbia

    Directory of Open Access Journals (Sweden)

    VLATKA VAJS

    2008-07-01

    Full Text Available Forensic practice in the Republic of Serbia faced the illegal production of amphetamine for the first time in 2003. This paper presents the results of the chemical characterization of 32 batches of amphetamine samples from three separate cases, for the purpose of identification of the active components and additives. Through the profiling of impurities of all samples, using gas chromatography/mass spectrometry (GC/MS, 30 compounds associated with amphetamine were identified. The results of the analysis of powder tartrate, sulfate and phosphate salts of amphetamine, as well as variously formulated tablets are presented in this study. The analyses showed that the amphetamines were synthesized by the Leuckart method in all cases.

  6. Amphetamines

    Science.gov (United States)

    ... unpredictably. Other long-term effects include: physical exhaustion insomnia and restlessness dizziness and blurred vision headaches reduced appetite and health problems from not eating properly higher chances of ...

  7. Amphetamine

    Science.gov (United States)

    ... along with a reduced calorie diet and an exercise plan for weight loss in obese people unable ... supplements you are taking, especially glutamic acid (L-glutamine).tell your doctor if you have hyperthyroidism (condition ...

  8. The effects of conditioning with amphetamine on the thermic effects of amphetamine and pentobarbital.

    Science.gov (United States)

    Hinson, R E; Streather, A; Cosburn, G

    1991-01-01

    1. Rats were injected with amphetamine (1.5 mg/kg) in the presence of a distinctive set of environmental stimuli (CS1) and saline in the presence of a different set of environmental stimuli (CS2) on different days for a total of 10 amphetamine and 20 saline injections. 2. The hyperthermic effect of amphetamine first increased but then declined to levels seen during the very first drug administration. 3. Following the conditioning phase, half the rats were injected with amphetamine in CS1 and half in CS2. Although there was little thermic effect of amphetamine injected in CS1, there was pronounced hyperthermia following amphetamine in CS2. 4. Next, pentobarbital (30 mg/kg) was administered to half the rats in CS1 and half in CS2. The hypothermic effect of pentobarbital was attenuated in CS2. PMID:1763195

  9. Biosynthesis of amphetamine analogs in plants.

    Science.gov (United States)

    Hagel, Jillian M; Krizevski, Raz; Marsolais, Frédéric; Lewinsohn, Efraim; Facchini, Peter J

    2012-07-01

    Amphetamine analogs are produced by plants in the genus Ephedra and by Catha edulis, and include the widely used decongestants and appetite suppressants pseudoephedrine and ephedrine. A combination of yeast (Candida utilis or Saccharomyces cerevisiae) fermentation and subsequent chemical modification is used for the commercial production of these compounds. The availability of certain plant biosynthetic genes would facilitate the engineering of yeast strains capable of de novo pseudoephedrine and ephedrine biosynthesis. Chemical synthesis has yielded amphetamine analogs with myriad functional group substitutions and diverse pharmacological properties. The isolation of enzymes with the serendipitous capacity to accept novel substrates could allow the production of substituted amphetamines in synthetic biosystems. Here, we review the biology, biochemistry and biotechnological potential of amphetamine analogs in plants. PMID:22502775

  10. Chronic amphetamine treatment increases striatal calmodulin in rats

    International Nuclear Information System (INIS)

    A radioimmunoassay was developed to measure calmodulin in striatum from rats treated with one dose or repeated injections of amphetamine. Chronic, but not acute, amphetamine treatment resulted in a significant increase in total calmodulin levels in striatal homogenates. This effect may be linked to the behavioral sensitization which develops after chronic amphetamine treatments. (Auth.)

  11. Determination of amphetamine by HPLC after acetylation.

    Science.gov (United States)

    Veress, T

    2000-01-01

    An analytical procedure has been developed for the HPLC determination of amphetamine by off-line pre-column derivatization. The proposed procedure consists of sample preparation by acetylation of amphetamine with acetic anhydride and a subsequent reversed-phase HPLC separation on an octadecyl silica stationary phase with salt-free mobile phase (tetrahydrofuran, acetonitrile, 0.1% triethylamine in water, 15:15:70 v/v) applying UV-detection. The applicability of the elaborated procedure is demonstrated with results obtained by analysis of real samples seized in the Hungarian black market. PMID:10641931

  12. Enantioselective degradation of amphetamine-like environmental micropollutants (amphetamine, methamphetamine, MDMA and MDA) in urban water.

    Science.gov (United States)

    Evans, Sian E; Bagnall, John; Kasprzyk-Hordern, Barbara

    2016-08-01

    This paper aims to understand enantioselective transformation of amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and MDA (3,4-methylenedioxyamphetamine) during wastewater treatment and in receiving waters. In order to undertake a comprehensive evaluation of the processes occurring, stereoselective transformation of amphetamine-like compounds was studied, for the first time, in controlled laboratory experiments: receiving water and activated sludge simulating microcosm systems. The results demonstrated that stereoselective degradation, via microbial metabolic processes favouring S-(+)-enantiomer, occurred in all studied amphetamine-based compounds in activated sludge simulating microcosms. R-(-)-enantiomers were not degraded (or their degradation was limited) which proves their more recalcitrant nature. Out of all four amphetamine-like compounds studied, amphetamine was the most susceptible to biodegradation. It was followed by MDMA and methamphetamine. Photochemical processes facilitated degradation of MDMA and methamphetamine but they were not, as expected, stereoselective. Preferential biodegradation of S-(+)-methamphetamine led to the formation of S-(+)-amphetamine. Racemic MDMA was stereoselectively biodegraded by activated sludge which led to its enrichment with R-(-)-enantiomer and formation of S-(+)-MDA. Interestingly, there was only mild stereoselectivity observed during MDMA degradation in rivers. This might be due to different microbial communities utilised during activated sludge treatment and those present in the environment. Kinetic studies confirmed the recalcitrant nature of MDMA. PMID:27182976

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

    OpenAIRE

    Grund, Jean-Paul; Coffin, Philip; Jauffret-Roustide, Marie; Dijkstra, Minke; Bruin, Dick; 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 effects, including amphetamine, methamphetamine, methcathinone and cathinone and referred to as ‘amphetamines’ in this review (Holman, 1994). MDMA (3,4-methylenedioxy-N-methamphetamine or ecstasy) is a ...

  14. 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.

  15. Raman Optical Activity and Raman Spectra of Amphetamine Species

    DEFF Research Database (Denmark)

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

    2012-01-01

    -molecular orbital calculations by use of the Gaussian 03W pro- gram, based on complete geometry minimizations of the conformational energy of the S-(+)-amphetamine molecule, the S-(+)-amphetamine-H+ ion, and the R-(–)-amphetamine molecule. Following this, harmonic frequency calculations have been made, providing...... am- phetamine-H+ sulfate. According to the present study the AMPH+ ion in aqueous sulfate solution seems to adopt a con- formation in which the phenyl and ammonium groups are in transpositions, similar to what has been found in the solid state....

  16. Intracerebral haemorrhage and vasculitis secondary to amphetamine use.

    OpenAIRE

    Salanova, V.; Taubner, R.

    1984-01-01

    We report a case of amphetamine-related intracranial haemorrhage and vasculitis, responding to immunosuppressants. Angiograms obtained before and after therapy are shown; the importance of immunosuppressive therapy is discussed.

  17. Amphetamines, the pregnant woman and her children: a review.

    Science.gov (United States)

    Oei, J L; Kingsbury, A; Dhawan, A; Burns, L; Feller, J M; Clews, S; Falconer, J; Abdel-Latif, M E

    2012-10-01

    The objective of this study is to review and summarize available evidence regarding the impact of amphetamines on pregnancy, the newborn infant and the child. Amphetamines are neurostimulants and neurotoxins that are some of the most widely abused illicit drugs in the world. Users are at high risk of psychiatric co-morbidities, and evidence suggests that perinatal amphetamine exposure is associated with poor pregnancy outcomes, but data is confounded by other adverse factors associated with drug-dependency. Data sources are Government data, published articles, conference abstracts and book chapters. The global incidence of perinatal amphetamine exposure is most likely severely underestimated but acknowledged to be increasing rapidly, whereas exposure to other drugs, for example, heroin, is decreasing. Mothers known to be using amphetamines are at high risk of psychiatric co-morbidity and poorer obstetric outcomes, but their infants may escape detection, because the signs of withdrawal are usually less pronounced than opiate-exposed infants. There is little evidence of amphetamine-induced neurotoxicity and long-term neurodevelopmental impact, as data is scarce and difficult to extricate from the influence of other factors associated with children living in households where one or more parent uses drugs in terms of poverty and neglect. Perinatal amphetamine-exposure is an increasing worldwide concern, but robust research, especially for childhood outcomes, remains scarce. We suggest that exposed children may be at risk of ongoing developmental and behavioral impediment, and recommend that efforts be made to improve early detection of perinatal exposure and to increase provision of early-intervention services for affected children and their families. PMID:22652562

  18. Effects of d-amphetamine upon psychosocial stress responses.

    Science.gov (United States)

    Childs, Emma; Bershad, Anya K; de Wit, Harriet

    2016-07-01

    Psychostimulant drugs alter the salience of stimuli in both laboratory animals and humans. In animals, stimulants increase rates of responding to conditioned incentive stimuli, and in humans, amphetamine increases positive ratings of emotional images. However, the effects of stimulants on real-life emotional events have not been studied in humans. In this study, we examined the effect of d-amphetamine on responses to acute psychosocial stress using a public speaking task. Healthy volunteers (N=56) participated in two experimental sessions, one with a psychosocial stressor (the Trier Social Stress Test) and one with a non-stressful control task. They were randomly assigned to receive d-amphetamine (5 mg n=18, 10 mg n=20) or placebo (n=18) on both sessions under double blind conditions. Salivary cortisol, subjective mood, and vital signs were measured at regular intervals during the session. Subjects also provided cognitive appraisals of the tasks before and after their performances. Amphetamine produced its expected mood and physiological effects, and the Trier Social Stress Test produced its expected effects on cortisol and mood. Although neither dose of amphetamine altered cardiovascular or hormonal responses to stress, amphetamine (10 mg) increased participants' pre-task appraisals of how challenging the task would be, and it increased post-task ratings of self-efficacy. Paradoxically, it also increased ratings of how stressful the task was, and prolonged aversive emotional responses. These findings suggest that amphetamine differentially affects stress response components: it may increase participants' appraisals of self-efficacy without dampening the direct emotional or physiological responses to the stress. PMID:27235381

  19. Stereoselective biodegradation of amphetamine and methamphetamine in river microcosms.

    Science.gov (United States)

    Bagnall, John; Malia, Louis; Lubben, Anneke; Kasprzyk-Hordern, Barbara

    2013-10-01

    Here presented for the first time is the enantioselective biodegradation of amphetamine and methamphetamine in river microcosm bioreactors. The aim of this investigation was to test the hypothesis that mechanisms governing the fate of amphetamine and methamphetamine in the environment are mostly stereoselective and biological in nature. Several bioreactors were studied over the duration of 15 days (i) in both biotic and abiotic conditions, (ii) in the dark or exposed to light and (iii) in the presence or absence of suspended particulate matter. Bioreactor samples were analysed using SPE-chiral-LC-(QTOF)MS methodology. This investigation has elucidated the fundamental mechanism for degradation of amphetamine and methamphetamine as being predominantly biological in origin. Furthermore, stereoselectivity and changes in enantiomeric fraction (EF) were only observed under biotic conditions. Neither amphetamine nor methamphetamine appeared to demonstrate adsorption to suspended particulate matter. Our experiments also demonstrated that amphetamine and methamphetamine were photo-stable. Illicit drugs are present in the environment at low concentrations but due to their pseudo-persistence and non-racemic behaviour, with two enantiomers revealing significantly different potency (and potentially different toxicity towards aquatic organisms) the risk posed by illicit drugs in the environment should not be under- or over-estimated. The above results demonstrate the need for re-evaluation of the procedures utilised in environmental risk assessment, which currently do not recognise the importance of the phenomenon of chirality in pharmacologically active compounds. PMID:23886544

  20. 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.

  1. Concurrent use of amphetamine stimulants and antidepressants by undergraduate students

    Directory of Open Access Journals (Sweden)

    Vo K

    2015-01-01

    Full Text Available Kim Vo,1 Patricia J Neafsey,2 Carolyn A Lin3 1University of Connecticut Health Center, Farmington, 2School of Nursing and Center for Health Information and Prevention, University of Connecticut, Storrs, 3Department of Communication Sciences and Center for Health Information and Prevention, University of Connecticut, Storrs, CT, USA Abstract: Undergraduate students were recruited to participate in an online survey to report their use of amphetamine stimulants and other drugs. Significant differences were found between students reporting (n=79; 4.0% and not reporting (n=1,897; 96% amphetamine-stimulant use in the past month – in terms of race/ethnicity, class standing, residence, health symptoms, self-health report – in addition to alcohol, tobacco, pain-reliever, and antidepressant use. Health symptoms reported more often by stimulant users included depression, diarrhea, difficulty sleeping, fatigue, dizziness, difficulty concentrating, and nicotine craving. Health care providers of college students should query these patients about symptoms that could be related to depression and amphetamine use. In particular, they should provide education at the point of care around the risks of amphetamine use in general and the specific risks in those students who have symptoms of depression and/or are taking antidepressant medication. Prevention programs should also target the risks of concurrent use of amphetamines, antidepressants, and other drugs among college students. Keywords: stimulant use, depression, college students, self-medication

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

    OpenAIRE

    Bramness Jørgen G; Gundersen Øystein; Guterstam Joar; Rognli Eline; Konstenius Maija; Løberg Else-Marie; Medhus Sigrid; Tanum Lars; Franck Johan

    2012-01-01

    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 amphetamine...

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

    OpenAIRE

    Jørgen G. Bramness; Gundersen, Øystein H.; Guterstam, Joar; Rognli, Eline B.; Konstenius, Maija; Løberg, Else-Marie; Medhus, Sigrid; Tanum, Lars; Franck, Johan

    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 t...

  4. Attention performance among Brazilian truck drivers and its association with amphetamine use: pilot study

    Directory of Open Access Journals (Sweden)

    Lucio Garcia de Oliveira

    2013-10-01

    Full Text Available The aim of this article was to describe the attention functioning of twenty-two truck drivers and its relationship with amphetamine use. Those drivers who reported using amphetamines in the twelve months previous to the interview had the best performance in a test evaluating sustained attention functioning. Although amphetamine use may initially seem advantageous to the drivers, it may actually impair safe driving. The findings suggest the importance of monitoring the laws regarding amphetamine use in this country.

  5. Apparent hallucinations in monkeys during around-the-clock amphetamine for seven to fourteen days. Possible relevance to amphetamine psychosis.

    Science.gov (United States)

    Nielsen, E B; Lyon, M; Ellison, G

    1983-04-01

    Schizophrenia-like symptoms have been experimentally produced in humans by a single, large dose of amphetamine or by relatively low level, but continuous administration of the drug. In animal studies of the psychotomimetic properties of amphetamine, high doses and, in particular, repeated daily-injection drug schedules have often been used. However, amphetamine psychosis is not always a prominent effect of repeated intake drug schedules in humans and available clinical evidence suggests that psychosis develops more readily when the drug is taken in a continuous fashion over longer periods. The state produced by single large doses of amphetamine, although clearly abnormal, has been said to bear less resemblance to schizophrenia than the delayed paranoid symptoms developing after longer periods of continuous intake. In the present experiments we have studied the behavioral effects of 7 to 14 days of continuous administration of amphetamine to monkeys (Cercopithecus aethiops) using subcutaneously implanted silicone capsules releasing approximately .7 to 1.5 mg/kg/day of d-amphetamine base. Around-the-clock TV monitoring of the animals revealed a general biphasic sequence of drug effects, although considerable individual variation occurred: a) an "acute" phase dominated by stereotyped movements and/or prolonged staring, lasting for 2 to 5 days; b) a "late" phase peaking during days 5 to 10 after capsule implantation and characterized by highly individual, but striking sequences of: (1) Attack or sudden threat reactions directed at invisible objects; (2) rapid orienting and flight behavior without apparent cause; (3) sudden startle reactions; (4) prolonged vocalization; (5) visual tracking of invisible objects, sometimes involving coordinated patterns of "eating behavior" and (6) prolonged and rapid grooming directed at various parts of the body. These behaviors might be termed "hallucinatory" since no eliciting stimuli could be determined for their occurrence. Motor

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

    International Nuclear Information System (INIS)

    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 (3600) 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.)

  7. Amphetamine alters neural response to sucrose in healthy women.

    Science.gov (United States)

    Melrose, A James; Bailer, Ursula; Wierenga, Christina E; Bischoff-Grethe, Amanda; Paulus, Martin P; Kaye, Walter H

    2016-06-30

    Amphetamine, likely via action on the brain's dopaminergic systems, induces anorectic eating behavior and blunts dopaminergic midbrain activation to rewards. Past work has hypothesized that this blunted reward responsivity is a result of increasing tonic over phasic DA activity. We sought to extend past findings to sweet taste during fMRI following single-blind administration of dextroamphetamine and placebo in 11 healthy women. We hypothesized that neural response in both limbic and cognitive sweet taste circuits would mirror past work with monetary rewards by effectively blunting sweet taste reward, and 'equalizing' it's rewarding taste with receipt of water. Behavioral results showed that amphetamine reduced self-reported hunger (supporting the existence of amphetamine anorexia) and increased self-report euphoria. In addition, region of Interest analysis revealed significant treatment by taste interactions in the middle insula and dorsal anterior cingulate confirming the 'equalizing' hypothesis in the cingulate, but unlike monetary reinforcers, the insula actually evinced enhanced separation between tastes on the amphetamine day. These results suggest a divergence from prior research using monetary reinforcers when extended to primary reinforcers, and may hint that altering dopaminergic signaling in the insula and anterior cingulate may be a target for pharmacological manipulation of appetite, and the treatment of obesity. PMID:27179312

  8. Impurities in Illicit Drug Preparations: Amphetamine and Methamphetamine.

    Science.gov (United States)

    Verweij, A M

    1989-06-01

    In this review, attention is paid to chromatographic and mass spectral properties of already identified impurities found to be present in frequently abused drug preparations of illegal origin of amphetamine and methamphetamine. The most commonly employed methods of synthesis of drugs of this type are briefly described. Special emphasis is given to the Leuckart route, found to be the preferred method, in the illicit production of amphetamine. Furthermore, some isolation and preconcentration methods for the contaminants are discussed. The importance of identifying impurities present in amphetamine or methamphetamine cannot be overestimated. These impurities originate mostly from the improper purification in the end stage of the different syntheses used in the clandestine manufacture of the substances; it is possible to differentiate between the several kinds of illegal drug preparations, synthesized by various methods, by means of so-called "route specific" impurities. Finally, a survey is given of the impurities already known to be present in amphetamine and methamphetamine, together with their mass spectral and some chromatographic properties. PMID:26266521

  9. Dexamethasone mimicks the antimotion sickness effects of amphetamine and scopolamine

    Science.gov (United States)

    Kohl, Randall Lee

    Based on preliminary suggestions that individual differences in susceptibility to stressful motion might be related to physiological differences in responses of the hypothalamic-pituitary-adrenal axis, we tested the efficacy of dexamethasone and metyrapone in subjects exposed to cross-coupled accelerative semicircular canal stimulation on a rotating chair. Subjects given 0.5 mg of dexamethasone every 6 h for 48 h could endure 80% more stressful motion ( P = 0.03) in a within-subjects design study, whereas, no improvement followed treatment with 750 mg of metryapone every 4 h for 24 h. The efficacy of dexamethasone might be explained in terms of its neurochemical actions on several neurotransmitter systems which are also modulated by such classical antimotion sickness drugs as amphetamine and scopolamine. Because dexamethasone induces adaptive changes within the central nervous system it may prove superior to scopolamine and amphetamine which possess significant side effects, are short acting, and rapidly tolerated.

  10. Epigenetic landscape of amphetamine and methamphetamine addiction in rodents

    OpenAIRE

    Godino, Arthur; Jayanthi, Subramaniam; Cadet, Jean Lud

    2015-01-01

    Amphetamine and methamphetamine addiction is described by specific behavioral alterations, suggesting long-lasting changes in gene and protein expression within specific brain subregions involved in the reward circuitry. Given the persistence of the addiction phenotype at both behavioral and transcriptional levels, several studies have been conducted to elucidate the epigenetic landscape associated with persistent effects of drug use on the mammalian brain. This review discusses recent advanc...

  11. Concurrent use of amphetamine stimulants and antidepressants by undergraduate students

    OpenAIRE

    Vo K; Neafsey PJ; Lin CA

    2015-01-01

    Kim Vo,1 Patricia J Neafsey,2 Carolyn A Lin3 1University of Connecticut Health Center, Farmington, 2School of Nursing and Center for Health Information and Prevention, University of Connecticut, Storrs, 3Department of Communication Sciences and Center for Health Information and Prevention, University of Connecticut, Storrs, CT, USA Abstract: Undergraduate students were recruited to participate in an online survey to report their use of amphetamine stimulants and other drugs. Signif...

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

    OpenAIRE

    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 ...

  13. Epigenetic landscape of amphetamine and methamphetamine addiction in rodents.

    Science.gov (United States)

    Godino, Arthur; Jayanthi, Subramaniam; Cadet, Jean Lud

    2015-01-01

    Amphetamine and methamphetamine addiction is described by specific behavioral alterations, suggesting long-lasting changes in gene and protein expression within specific brain subregions involved in the reward circuitry. Given the persistence of the addiction phenotype at both behavioral and transcriptional levels, several studies have been conducted to elucidate the epigenetic landscape associated with persistent effects of drug use on the mammalian brain. This review discusses recent advances in our comprehension of epigenetic mechanisms underlying amphetamine- or methamphetamine-induced behavioral, transcriptional, and synaptic plasticity. Accumulating evidence demonstrated that drug exposure induces major epigenetic modifications-histone acetylation and methylation, DNA methylation-in a very complex manner. In rare instances, however, the regulation of a specific target gene can be correlated to both epigenetic alterations and behavioral abnormalities. Work is now needed to clarify and validate an epigenetic model of addiction to amphetamines. Investigations that include genome-wide approaches will accelerate the speed of discovery in the field of addiction. PMID:26023847

  14. 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.

  15. [Study on the optimization methods of common-batch identification of amphetamine samples].

    Science.gov (United States)

    Zhang, Jianxin; Zhang, Daming

    2008-07-01

    The essay introduced the technology of amphetamine identification and its optimization method. Impurity profiling of amphetamine was analyzed by GC-MS. Identification of common-batch amphetamine samples could be successfully finished by the data transition and pre-treating of the peak areas. The analytical method was improved by optimizing the techniques of sample extraction, gas chromatograph, sample separation and detection. PMID:18839544

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

    OpenAIRE

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

    2006-01-01

    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 ...

  17. Development of a harmonised method for the profiling of amphetamines VI: Evaluation of methods for comparison of amphetamine.

    Science.gov (United States)

    Andersson, Kjell; Lock, Eric; Jalava, Kaisa; Huizer, Henk; Jonson, Sten; Kaa, Elisabet; Lopes, Alvaro; Poortman-van der Meer, Anneke; Sippola, Erkki; Dujourdy, Laurence; Dahlén, Johan

    2007-06-14

    Amphetamine samples were analysed by gas chromatography-mass spectrometry (GC-MS), and the peak areas of 33 target compounds were transformed by applying various pretreatment techniques. The objective was to optimise the ability of a number of distance metrics to establish links between samples of amphetamine originating from the same batch (henceforth referred to as linked distances). Furthermore, partial least squares discriminant analysis (PLS-DA) was used to evaluate the effects of various pretreatment methods on separation of amphetamine batches synthesised by the Leuckart reaction, reductive amination of benzyl methyl ketone, and the nitrostyrene route. The most efficient way to pretreat GC-MS data varied for the different distance metrics, although best results were obtained when data were normalised to the sum of peak areas, and either the fourth root or a logarithm was applied to the normalised data. When pretreating normalised data by fourth root transformation, Pearson correlation was the distance metric that was most successful at finding linked samples. Normalisation and the use of fourth root also represented the best method of pretreating data when employing PLS-DA to separate samples synthesised by different routes. To achieve a faster and more user-friendly procedure for evaluating chromatograms, experiments were performed in which the number of target compounds used to compare samples was reduced. The effect of each compound that was removed was studied by applying PLS-DA and by using Pearson correlation to calculate linked distances as well as unlinked distances (between samples from different batches of amphetamine). Considering both links between samples from the same batch and separation of samples synthesised by different routes, the best results were obtained with the data set comprising 26 compounds. Finally, it was found that the profiling method developed in this work was superior to an existing technique with respect to separating linked

  18. 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.

  19. 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)

    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

  20. Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class

    OpenAIRE

    Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian

    2011-01-01

    The demonstrated ability of amphetamine to functionally activate the rat trace amine associated receptor 1 (rTAAR1) and the subsequent reports of amphetamine activation of TAAR1 in rhesus monkey mouse, human, and human-rat chimeric TAAR1-expressing cell lines has led to speculation as to the role of this receptor in the central nervous system (CNS) responses associated with amphetamine and its analogs. The agonist potencies of ten pairs of enantiomeric amphetamines, including several with kno...

  1. Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine-like cathinone, cathine or norephedrine

    OpenAIRE

    Bredholt, Therese; Ersvær, Elisabeth; Erikstein, Bjarte Skoe; Sulen, André; Reikvam, Håkon; Aarstad, Hans Jørgen; Johannessen, Anne Christine; Vintermyr, Olav Karsten; Bruserud, Øystein; Gjertsen, Bjørn Tore

    2013-01-01

    Background: Amphetamine and amphetamine derivatives are suggested to induce an immunosuppressive effect. However, knowledge of how amphetamines modulate intracellular signaling pathways in cells of the immune system is limited. We have studied phosphorylation of signal transduction proteins (Akt, CREB, ERK1/2, NF-κB, c-Cbl, STAT1/3/5/6) and stress sensors (p38 MAPK, p53) in human leukocyte subsets following in vitro treatment with the natural amphetamine cathinone, the cathinone d...

  2. Amphetamine elicits opposing actions on readily releasable and reserve pools for dopamine.

    Directory of Open Access Journals (Sweden)

    Dan P Covey

    Full Text Available 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.

  3. Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice 1,2,3

    OpenAIRE

    Storey, Granville P; Gonzalez-Fernandez, Gabriel; Bamford, Ian J.; Hur, Matthew; McKinley, Jonathan W.; Heimbigner, Lauren; Minasyan, Ani; 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 promo...

  4. The relationship of quality and price of the psychostimulants cocaine and amphetamine with health care outcomes

    NARCIS (Netherlands)

    T.M. Brunt; M. van Laar; R.J.M. Niesink; W. van den Brink

    2010-01-01

    A major component of the illicit drug market can be subcategorized as the psychostimulant drug market, with cocaine and amphetamine as popular constituents. In The Netherlands, an increase in both health care outcomes addiction treatment and hospital admissions was noted for both amphetamine and coc

  5. Functional magnetic resonance imaging investigation of the amphetamine sensitization model of schizophrenia in healthy male volunteers

    OpenAIRE

    O'Daly, Owen G; Joyce, Daniel; Stephan, Klaas E.; Murray, Robin M G; Shergill, Sukhwinder S.

    2011-01-01

    These transient load-dependent abnormalities of frontal and temporal activity induced by amphetamine sensitization support neuroimaging findings in schizophrenic patients, implying that amphetamine sensitization may help to bridge pathophysiological theories of schizophrenia that focus on pharmacological (dopaminergic) and cognitive mechanisms, respectively.

  6. 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.

  7. 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

    Directory of Open Access Journals (Sweden)

    Rabe-Jabłońska, Jolanta

    2012-08-01

    Full Text Available 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 amphetamine users with amphetamine induced schizophrenia – like psychosis, 30 amphetamine users with schizophrenia and 30 amphetamine users without psychotic symptoms (37 female and 53 male in mean age=17.78 years . Methods. Amphetamine dependence, schizophrenia and schizophrenia-like psychosis induced amphetamine were diagnosed according to ICD-10 criteria after at least 1 year of amphetamine abstinence. The next procedure was used: 1 Structured interview with subjects and their mothers/caregivers regarding: a amphetamines use (duration of abuse, doses of psychoactive substance b family history of psychosis (especially schizophrenia 2 The Questionnaire of Child Development for assessment of prevalence of selected risk factors of schizophrenia development 3 The Premorbid Adjustment Scale (Cannon – Spoor for assessment of premorbid psychosocial functioning in thelast year before psychosis. Conclusions. Amphetamines users with amphetamine-induced psychosis were more similar in prevalence of selective risk factors of schizophrenia development to subjects with schizophrenia and amphetamine dependence than to amphetamine users without psychosis. Amphetamine-induced psychosis developed more frequently in amphetamine users who used higher amphetamine doses and with familial history of psychosis.

  8. 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...

  9. Depression, craving and amphetamine use: Findings from a study on the efficacy of extended release naltrexone for treating amphetamine dependence in Iceland

    OpenAIRE

    Krantz, Sofia Birgitta, 1983-

    2014-01-01

    Amphetamine dependence is a serious, growing problem around the world and Iceland is no exception. Neuropsychological theory, animal studies and a few clinical studies suggest that naltrexone might be beneficial in the treatment of amphetamine dependence. However, depression might affect outcomes in treatment of substance dependence. In the current study, 32 participants were followed six months after completing a 24 week randomized, placebo-controlled, double-blind clinical trial testing the...

  10. 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...... with internal bonds (sulfates, hydrogen phosphates, etc.) need to be taken into account when employing these spectra for identification purposes. These results also show how Raman spectroscopy can assist the forensic community in drug profiling studies. Furthermore, because their spectra are different...

  11. Radiohalogenated amphetamine analogs for blood flow and serotonin receptor studies

    International Nuclear Information System (INIS)

    The 4-radiohalo-2,5-dimethoxyamphetamine hallucinogens were first utilized in the 1970's for cerebral imaging studies by T. Sargent and A.T. Shulgin. Subsequently, other radioiodinated amphetamine analogs and distantly related diamines have been synthesized and used for clinical single photon studies of cerebral blood flow. A generator system for the production of the short-lived positron emitter 122I (3.5 min half-life) was developed, and several amphetamine and diamine compounds have been labeled with 122I for positron emission tomography (PET) studies of regional cerebral blood flow in animals and humans. The short half-life of 122I requires that the radiochemical syntheses be rapid and efficient. Both electrophilic deprotonation and demetallation reactions have been utilized to achieve this goal. Recently, there has been considerable evidence that some 4-halo-2,5-dimethoxyamphetamine analogs are highly specific serotonin receptor agonists. This has lead to the speculation that the binding of these agonists to a serotonin 5-HT2 receptor sub-type may be involved in hallucinogenesis. In an effort to help elucidate the role of these agents, several radioiodinated and radiobrominated 4-halo-2,5-dimethoxyamphetamine analogs have been synthesized for in vitro binding studies. Studies examining the in vivo interaction of these analogs with serotonin 5-HT2 receptors have been initiated with the synthesis of 4-(18F)fluoroalkyl-2,5-dimethoxyamphetamines

  12. 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. PMID:14640484

  13. ELISA Detection of 30 New Amphetamine Designer Drugs in Whole Blood, Urine and Oral Fluid using Neogen® "Amphetamine" and "Methamphetamine/MDMA" Kits.

    Science.gov (United States)

    Nieddu, Maria; Burrai, Lucia; Baralla, Elena; Pasciu, Valeria; Varoni, Maria Vittoria; Briguglio, Irene; Demontis, Maria Piera; Boatto, Gianpiero

    2016-09-01

    Amphetamine designer drugs are central nervous system stimulants that are widely disseminated in the illegal market. Generally, in forensic laboratories, immunoassay methods are the first line of screening for these types of drugs in a biological specimen (typically blood, urine or oral fluid). In this article, we describe the cross-reactivity profiles of 30 new amphetamine designer drugs, using the Neogen(®) [Amphetamine Specific and Methamphetamine/3,4-Methylenedioxymethamphetamine (MDMA) assays] drug tests. To assess the potential matrix influence on the response, each assay was tested on whole blood, urine and oral fluid. Concentrations of 10,000 ng/mL were not sufficient to produce a positive response for the majority of the analyzed amphetamines. This clearly demonstrates that, although these kits are extremely effective for the target drugs for which they are intended (amphetamine, methamphetamine and MDMA), they cannot be used to reliably identify the tested designer drugs in real cases, as these concentrations greatly exceed those expected to be found in forensic samples. PMID:27405364

  14. In vivo amphetamine action is contingent on αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Mus, Liudmilla; Eisenrauch, Birgit; Constantinescu, Andreea; Leo, Damiana; Konrad, Lisa; Rickhag, Karl Mattias; Sørensen, Gunnar; Efimova, Evgenia V; Kong, Eryan; Willeit, Matthäus; Sotnikova, Tatyana D; Kudlacek, Oliver; Gether, Ulrik; Freissmuth, Michael; Pollak, Daniela D; Gainetdinov, Raul R; Sitte, Harald H

    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 for...

  15. Comparative Cardiac Risks of Methylphenidate and Amphetamines in Treatment of ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-08-01

    Full Text Available The risk for adverse cardiac events in subjects between 3 and 20 years of age treated with methylphenidate or amphetamine salts for ADHD was determined in a retrospective study at University of Florida, Gainesville, FL.

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

    Science.gov (United States)

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

    2016-02-01

    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 amphetamine in the discriminative stimulus effects of methamphetamine in rhesus monkeys. Adult male rhesus monkeys (n=3) were trained to discriminate 0.18mg/kg intramuscular (+)-methamphetamine from saline in a two-key food-reinforced discrimination procedure. Time course of saline, (+)-methamphetamine (0.032-0.32mg/kg), and (+)-amphetamine (0.032-0.32mg/kg) discriminative stimulus effects were determined. Parallel pharmacokinetic studies were conducted in the same monkeys to determine plasma methamphetamine and amphetamine levels after methamphetamine administration and amphetamine levels after amphetamine administration for correlation with behavior in the discrimination procedure. Both methamphetamine and amphetamine produced full, ≥90%, methamphetamine-like discriminative stimulus effects. Amphetamine displayed a slightly, but significantly, longer duration of action than methamphetamine in the discrimination procedure. Both methamphetamine and amphetamine behavioral effects were related to methamphetamine and amphetamine plasma levels by a clockwise hysteresis loop indicating acute tolerance had developed to the discriminative stimulus effects. Furthermore, amphetamine levels after methamphetamine administration were absent when methamphetamine stimulus effects were greatest and peaked when methamphetamine discriminative stimulus effects returned to saline-like levels. Overall, these results demonstrate the methamphetamine metabolite amphetamine does not contribute to

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

    OpenAIRE

    Hossein Kaviani

    2006-01-01

    "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 dr...

  18. Behavioural and molecular responses to amphetamine in the neurokinin-1 receptor knock-out mouse

    OpenAIRE

    Slone-Murphy, J.

    2011-01-01

    The neurokinin-1 receptor knock-out (NK1R-/-) mouse is hyperactive and shows deficits in attentional processing, and has recently been put forward as a model of attention deficit hyperactivity disorder (ADHD). Acute amphetamine, a first-line treatment for ADHD and a drug of abuse, paradoxically reduces the hyperactivity of NK1R-/- mice, and the characteristic amphetamine-stimulated increase in striatal dopamine efflux seen in wild-type animals is attenuated in NK1R-/- mice. The...

  19. Serotonergic neurotransmission in the ventral hippocampus is enhanced by corticosterone and altered by chronic amphetamine treatment

    OpenAIRE

    Barr, Jeffrey L.; Forster, Gina L.

    2011-01-01

    The ventral hippocampus modulates anxiety-like behavior in rats, and serotonergic transmission within the hippocampus facilitates adaptation to stress. Chronic amphetamine treatment results in anxiety-like behavior in rats and reduced monoamine concentrations in the ventral hippocampus. Since reduced hippocampal serotonergic transmission in response to stress is observed in rats that display high anxiety-like behavior, anxiety states in amphetamine-treated rats may be associated with reduced ...

  20. Dopaminergic Actions of D-Amphetamine on Schedule-Induced Polydipsia in Rats

    Science.gov (United States)

    Pellon, Ricardo; Ruiz, Ana; Rodriguez, Cilia; Flores, Pilar

    2007-01-01

    Schedule-induced polydipsia in rats was developed by means of a fixed-time 60-s schedule of food presentation. The acute administration of d-amphetamine sulfate (0.1-3.0 mg/kg) produced a dose-dependent decrease in the rate of licking. D-Amphetamine shifted to the left the temporal distribution of adjunctive drinking within interfood intervals.…

  1. Effect of dexamethasone on protein extravasation in the brain in acute hypertension induced by amphetamine

    International Nuclear Information System (INIS)

    Amphetamine produces protein leakage in the brain when given to rats under nitrous oxide anesthesia. The blood-brain barrier dysfunction is caused by the combined effect of blood pressure increase and vasodilatation. In the present experiments pretreatment with dexamethasone, 2 mg. kg-1, diminished the amphetamine-induced extravasation of Evans blue albumin and 125IHSA in the rats' brain. Possible explanations to the effect of dexamethasone on cerebrovascular permeability are discussed. (author)

  2. Adolescent social defeat alters neural, endocrine and behavioral responses to amphetamine in adult male rats

    OpenAIRE

    Burke, Andrew R.; Renner, Kenneth J.; Forster, Gina L.; Watt, Michael J.

    2010-01-01

    The mesocorticolimbic dopamine system, which governs components of reward and goal-directed behaviors, undergoes final maturation during adolescence. Adolescent social stress contributes to adult behavioral dysfunction, and is linked to adult psychiatric and addiction disorders. Here, behavioral, corticosterone, and limbic dopamine responses to amphetamine were examined in adult male rats previously exposed to repeated social defeat stress during mid-adolescence. Amphetamine (2.5 mg/kg, ip) w...

  3. MRI reveals differential effects of amphetamine exposure on neuroglia in vivo

    OpenAIRE

    Liu, Christina H.; Yang, Jinsheng; Ren, Jia Q.; Liu, Charng-Ming; You, Zerong; LIU, PHILIP K.

    2013-01-01

    How amphetamine affects the neuroglia in living brains is not well understood. In an effort to elucidate this effect, we investigated neuroglia in response to amphetamine exposure using antisense (AS) or sense (S) phosphorothioate-modified oligodeoxynucleotide (sODN) sequences that correspond to glial fibrillary acidic protein (GFAP) mRNA (AS-gfap or S-gfap, respectively) expression. The control is a random-sequence sODN (Ran). Using cyanine 5.5-superparamagnetic iron oxide nanoparticle (Cy5....

  4. Schizophrenia, amphetamine-induced sensitized state and acute amphetamine exposure all show a common alteration: increased dopamine D2 receptor dimerization

    Directory of Open Access Journals (Sweden)

    Wang Min

    2010-09-01

    Full Text Available Abstract Background All antipsychotics work via dopamine D2 receptors (D2Rs, suggesting a critical role for D2Rs in psychosis; however, there is little evidence for a change in receptor number or pharmacological nature of D2Rs. Recent data suggest that D2Rs form dimers in-vitro and in-vivo, and we hypothesized that schizophrenia, as well as preclinical models of schizophrenia, would demonstrate altered dimerization of D2Rs, even though the overall number of D2Rs was unaltered. Methods We measured the expression of D2Rs dimers and monomers in patients with schizophrenia using Western blots, and then in striatal tissue from rats exhibiting the amphetamine-induced sensitized state (AISS. We further examined the interaction between D2Rs and the dopamine transporter (DAT by co-immunoprecipitation, and measured the expression of dopamine D2High receptors with ligand binding assays in rat striatum slices with or without acute amphetamine pre-treatment. Results We observed significantly enhanced expression of D2Rs dimers (277.7 ± 33.6% and decreased expression of D2Rs monomers in post-mortem striatal tissue of schizophrenia patients. We found that amphetamine facilitated D2Rs dimerization in both the striatum of AISS rats and in rat striatal neurons. Furthermore, amphetamine-induced D2Rs dimerization may be associated with the D2R-DAT protein-protein interaction as an interfering peptide that disrupts the D2R-DAT coupling, blocked amphetamine-induced up-regulation of D2Rs dimerization. Conclusions Given the fact that amphetamine induces psychosis and that the AISS rat is a widely accepted animal model of psychosis, our data suggest that D2R dimerization may be important in the pathophysiology of schizophrenia and may be a promising new target for novel antipsychotic drugs.

  5. A theoretical study on the interaction of amphetamine and single-walled carbon nanotubes

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • Interaction energy between several armchair CNTs and amphetamine is investigated. • The adsorption of amphetamine molecule is observed to be exothermic and physical in nature. • HOMO–LUMO for pure CNTs, amphetamine and their corresponded complexes are studied. • Density of states (DOS) near the Fermi level is calculated and presented. - Abstract: The adsorption of 1-phenyl-2-aminopropane (amphetamine) on the (4,4), (5,5), (6,6), and (7,7) single-walled carbon nanotubes (SWCNTs) has been theoretically investigated. The molecule has been located in different modes including parallel, perpendicular, and oblique on the outer surface of carbon nanotubes. The physisorption of amphetamine onto SWCNT sidewall is thermodynamically favored; as a consequence, it modulates the electronic properties of pristine nanotube in the vicinity of Fermi region. The adsorption energies for the parallel and oblique modes found in the range of −1.13 to −1.88 and −1.27 to −2.01 kcal/mol, respectively. Projected density of states (PDOS) and frontier orbital analysis in the vicinity of Fermi level region suggest the electronic states to be contributed from SWCNT rather than amphetamine molecule

  6. Amphetamine administration into the ventral striatum facilitates behavioral interaction with unconditioned visual signals in rats.

    Directory of Open Access Journals (Sweden)

    Rick Shin

    Full Text Available BACKGROUND: Administration of psychomotor stimulants like amphetamine facilitates behavior in the presence of incentive distal stimuli, which have acquired the motivational properties of primary rewards through associative learning. This facilitation appears to be mediated by the mesolimbic dopamine system, which may also be involved in facilitating behavior in the presence of distal stimuli that have not been previously paired with primary rewards. However, it is unclear whether psychomotor stimulants facilitate behavioral interaction with unconditioned distal stimuli. PRINCIPAL FINDINGS: We found that noncontingent administration of amphetamine into subregions of the rat ventral striatum, particularly in the vicinity of the medial olfactory tubercle, facilitates lever pressing followed by visual signals that had not been paired with primary rewards. Noncontingent administration of amphetamine failed to facilitate lever pressing when it was followed by either tones or delayed presentation or absence of visual signals, suggesting that visual signals are key for enhanced behavioral interaction. Systemic administration of amphetamine markedly increased locomotor activity, but did not necessarily increase lever pressing rewarded by visual signals, suggesting that lever pressing is not a byproduct of heightened locomotor activity. Lever pressing facilitated by amphetamine was reduced by co-administration of the dopamine receptor antagonists SCH 23390 (D1 selective or sulpiride (D2 selective. CONCLUSIONS: Our results suggest that amphetamine administration into the ventral striatum, particularly in the vicinity of the medial olfactory tubercle, activates dopaminergic mechanisms that strongly enhance behavioral interaction with unconditioned visual stimuli.

  7. A theoretical study on the interaction of amphetamine and single-walled carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Hafizi, Hamid [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Najafi Chermahini, Alireza, E-mail: anajafi@cc.iut.ac.ir [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Mohammadnezhad, Gholamhossein [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Teimouri, Abbas [Chemistry Department, Payame Noor University (PNU), Tehran 19395-4697 (Iran, Islamic Republic of)

    2015-02-28

    Graphical abstract: - Highlights: • Interaction energy between several armchair CNTs and amphetamine is investigated. • The adsorption of amphetamine molecule is observed to be exothermic and physical in nature. • HOMO–LUMO for pure CNTs, amphetamine and their corresponded complexes are studied. • Density of states (DOS) near the Fermi level is calculated and presented. - Abstract: The adsorption of 1-phenyl-2-aminopropane (amphetamine) on the (4,4), (5,5), (6,6), and (7,7) single-walled carbon nanotubes (SWCNTs) has been theoretically investigated. The molecule has been located in different modes including parallel, perpendicular, and oblique on the outer surface of carbon nanotubes. The physisorption of amphetamine onto SWCNT sidewall is thermodynamically favored; as a consequence, it modulates the electronic properties of pristine nanotube in the vicinity of Fermi region. The adsorption energies for the parallel and oblique modes found in the range of −1.13 to −1.88 and −1.27 to −2.01 kcal/mol, respectively. Projected density of states (PDOS) and frontier orbital analysis in the vicinity of Fermi level region suggest the electronic states to be contributed from SWCNT rather than amphetamine molecule.

  8. Combination of modafinil and d-Amphetamine for the treatment of cocaine dependence: A preliminary investigation

    Directory of Open Access Journals (Sweden)

    Joy M Schmitz

    2012-08-01

    Full Text Available Background: Two stimulant medications, modafinil and d-amphetamine, when tested individually, have shown safety and efficacy for treatment of cocaine addiction. We hypothesized that the combination of modafinil and d-amphetamine, at low doses, would show equivalent or greater benefit in reducing cocaine use compared to higher doses of each individual medication or placebo. Methods: Sixteen week, randomized, parallel-group design with four treatment arms comparing placebo to modafinil 400 mg; d-amphetamine 60 mg; modafinil 200 mg plus d-amphetamine 30 mg. Primary outcome variables, retention and cocaine use, were analyzed on the sample of 73 participants who received the first dose of the study medication. Results: Retention rates did not differ between groups and were generally low, with 40% remaining in treatment at week 12 and 20% at week 16. Participants receiving the combination of modafinil and d-amphetamine showed a trend of increased cocaine use over time with a corresponding low Bayesian probability of benefit (33%. Relatively better cocaine outcomes were observed in the placebo and d-amphetamine only groups. The study medications were generally well-tolerated with few adverse effects, yet rates of adherence were suboptimal (≤ 80%. Conclusion: Data from this preliminary investigation fail to provide evidential support for conducting a larger study of this dual-agonist medication combination for treatment of cocaine dependence.

  9. Learning and cross drug effects: thermic effects of pentobarbital and amphetamine.

    Science.gov (United States)

    Hinson, R E; Rhijnsburger, M

    1984-06-25

    The effects of environmental cues explicitly paired or unpaired with pentobarbital on the thermic effects of pentobarbital and amphetamine were investigated. Rats received 19 injections of pentobarbital in a distinctive environment and were subsequently tested for the thermic effects of pentobarbital and amphetamine in the distinctive environment, another environment previously associated only with saline, or in the colony room not previously associated with injections. Rats tested in the context of the environmental cues previously associated with pentobarbital were tolerant to the hypothermic effect of pentobarbital, but rats tested in the environment previously associated only with saline or in the colony room were not tolerant. Pentobarbital-experienced rats administered amphetamine in the context of the usual pentobarbital cues exhibited an exaggerated hyperthermic reaction compared to previously drug-naive rats administered amphetamine. Pentobarbital-experienced rats injected with amphetamine in the homeroom exhibited a smaller hyperthermic response than previously drug-naive rats administered amphetamine in the home room. These results demonstrate that an animal's response to a drug can be affected by cues paired and unpaired with drug administration. PMID:6738300

  10. The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D-amphetamine.

    Science.gov (United States)

    Steinkellner, Thomas; Freissmuth, Michael; Sitte, Harald H; Montgomery, Therese

    2011-01-01

    Amphetamine ('Speed'), methamphetamine ('Ice') and its congener 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') are illicit drugs abused worldwide for their euphoric and stimulant effects. Despite compelling evidence for chronic MDMA neurotoxicity in animal models, the physiological consequences of such toxicity in humans remain unclear. In addition, distinct differences in the metabolism and pharmacokinetics of MDMA between species and different strains of animals prevent the rationalisation of realistic human dose paradigms in animal studies. Here, we attempt to review amphetamine toxicity and in particular MDMA toxicity in the pathogenesis of exemplary human pathologies, independently of confounding environmental factors such as poly-drug use and drug purity. PMID:21194370

  11. 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.

  12. High estrogen and chronic haloperidol lead to greater amphetamine-induced BOLD activation in awake, amphetamine-sensitized female rats.

    Science.gov (United States)

    Madularu, Dan; Kulkarni, Praveen; Yee, Jason R; Kenkel, William M; Shams, Waqqas M; Ferris, Craig F; Brake, Wayne G

    2016-06-01

    The ovarian hormone estrogen has been implicated in schizophrenia symptomatology. Low levels of estrogen are associated with an increase in symptom severity, while exogenous estrogen increases the efficacy of antipsychotic medication, pointing at a possible interaction between estrogen and the dopaminergic system. The aim of this study is to further investigate this interaction in an animal model of some aspects of schizophrenia using awake functional magnetic resonance imaging. Animals receiving 17β-estradiol and haloperidol were scanned and BOLD activity was assessed in response to amphetamine. High 17β-estradiol replacement and chronic haloperidol treatment showed increased BOLD activity in regions of interest and neural networks associated with schizophrenia (hippocampal formations, habenula, amygdala, hypothalamus etc.), compared with low, or no 17β-estradiol. These data show that chronic haloperidol treatment has a sensitizing effect, possibly on the dopaminergic system, and this effect is dependent on hormonal status, with high 17β-estradiol showing the greatest BOLD increase. Furthermore, these experiments further support the use of imaging techniques in studying schizophrenia, as modeled in the rat, but can be extended to addiction and other disorders. PMID:27154458

  13. Personality and the subjective effects of acute amphetamine in healthy volunteers.

    Science.gov (United States)

    White, Tara L; Lott, David C; de Wit, Harriet

    2006-05-01

    Individual differences in the positive mood and other subjective effects of d-amphetamine have been linked to personality traits related to sensation seeking. The current study extends these associations to separate personality traits of reward sensitivity, physical fearlessness, and impulsivity. A total of 128 healthy volunteers received oral doses of d-amphetamine (10 and 20 mg) or placebo in counterbalanced order. Their responses to the drug were measured using the Profile of Mood States, Addiction Research Center Inventory, and Drug Effects Questionnaire. Participants completed the Multidimensional Personality Questionnaire Brief Form to assess personality traits related to reward sensitivity (Agentic Positive Emotionality and Social Potency (SP)), physical fear (Harm Avoidance (HA)), and impulsivity (Control (CL)). Participants were rank ordered on each trait, and individuals with scores in the top and bottom thirds of scores on each trait were compared using ANCOVA. High trait physical fearlessness (low HA) was associated with greater positive activational effects of 10 mg d-amphetamine. High trait reward sensitivity (high SP) was marginally associated with greater positive activational effects of 20 mg d-amphetamine. High trait impulsivity (low CL) was unrelated to positive drug effects in response either dose. The two separate personality traits of physical fearlessness and reward sensitivity are associated with d-amphetamine effects on mood in healthy volunteers. Implications for the vulnerability to psychostimulant addiction in healthy nonaddicts are discussed. PMID:16237380

  14. The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia

    International Nuclear Information System (INIS)

    To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p less than 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (p = -0.71; p less than 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity

  15. Effects of adolescent social defeat on adult amphetamine-induced locomotion and corticoaccumbal dopamine release in male rats

    OpenAIRE

    Burke, Andrew R.; Forster, Gina L.; Novick, Andrew M.; Roberts, Christina L.; Watt, Michael J.

    2012-01-01

    Maturation of mesocorticolimbic dopamine systems occurs during adolescence, and exposure to social stress during this period results in behavioral dysfunction including substance abuse disorders. Adult male rats exposed to repeated social defeat in adolescence exhibit reduced basal dopamine tissue content in the medial prefrontal cortex, altered dopamine tissue content in corticoaccumbal dopamine regions following acute amphetamine, and increased amphetamine conditioned place preference follo...

  16. 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.

  17. 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. PMID:21134359

  18. Development of a harmonised method for the profiling of amphetamines: IV. Optimisation of sample preparation.

    Science.gov (United States)

    Andersson, Kjell; Jalava, Kaisa; Lock, Eric; Huizer, Henk; Kaa, Elisabet; Lopes, Alvaro; Poortman-van der Meer, Anneke; Cole, Michael D; Dahlén, Johan; Sippola, Erkki

    2007-06-14

    The suitability of liquid-liquid extraction (LLE) and solid-phase extraction (SPE) for the preparation of impurity extracts intended for gas chromatographic profiling analyses of amphetamine were evaluated. Both techniques were optimised with respect to the extraction of selected target compounds by use of full factorial designs in which the variables affecting the performance were evaluated. Test samples consisted of amphetamine synthesised by the Leuckart reaction, by reductive amination of benzyl methyl ketone and by the nitrostyrene route. The performance of LLE and SPE were comparable in terms of repeatability and recovery of the target compounds. LLE was considered the better choice for the present harmonised amphetamine profiling method due to the lack of information on the long-term stability of SPE columns. PMID:17134863

  19. Occupational conditions and the risk of the use of amphetamines by truck drivers

    Science.gov (United States)

    de Oliveira, Lúcio Garcia; de Souza, Letícia Maria de Araújo; Barroso, Lúcia Pereira; Gouvêa, Marcela Júlio César; de Almeida, Carlos Vinícius Dias; Muñoz, Daniel Romero; Leyton, Vilma

    2015-01-01

    OBJECTIVE To test whether the occupational conditions of professional truck drivers are associated with amphetamine use after demographic characteristics and ones regarding mental health and drug use are controlled for. METHODS Cross-sectional study, with a non-probabilistic sample of 684 male truck drivers, which was collected in three highways in Sao Paulo between years 2012 and 2013. Demographic and occupational information was collected, as well as data on drug use and mental health (sleep quality, emotional stress, and psychiatric disorders). A logistic regression model was developed to identify factors associated with amphetamine use. Odds ratio (OR; 95%CI) was defined as the measure for association. The significance level was established as p < 0.05. RESULTS The studied sample was found to have an average age of 36.7 (SD = 7.8) years, as well as low education (8.6 [SD = 2.3] years); 29.0% of drivers reported having used amphetamines within the twelve months prior to their interviews. After demographic and occupational variables had been controlled for, the factors which indicated amphetamine use among truck drivers were the following: being younger than 38 years (OR = 3.69), having spent less than nine years at school (OR = 1.76), being autonomous (OR = 1.65), working night shifts or irregular schedules (OR = 2.05), working over 12 hours daily (OR = 2.14), and drinking alcohol (OR = 1.74). CONCLUSIONS Occupational aspects are closely related to amphetamine use among truck drivers, which reinforces the importance of closely following the application of law (Resting Act (“Lei do Descanso”); Law 12,619/2012) which regulates the workload and hours of those professionals. Our results show the need for increased strictness on the trade and prescription of amphetamines in Brazil. PMID:26398875

  20. Occupational conditions and the risk of the use of amphetamines by truck drivers

    Directory of Open Access Journals (Sweden)

    Lúcio Garcia de Oliveira

    2015-01-01

    Full Text Available OBJECTIVE To test whether the occupational conditions of professional truck drivers are associated with amphetamine use after demographic characteristics and ones regarding mental health and drug use are controlled for.METHODS Cross-sectional study, with a non-probabilistic sample of 684 male truck drivers, which was collected in three highways in Sao Paulo between years 2012 and 2013. Demographic and occupational information was collected, as well as data on drug use and mental health (sleep quality, emotional stress, and psychiatric disorders. A logistic regression model was developed to identify factors associated with amphetamine use. Odds ratio (OR; 95%CI was defined as the measure for association. The significance level was established as p < 0.05.RESULTS The studied sample was found to have an average age of 36.7 (SD = 7.8 years, as well as low education (8.6 [SD = 2.3] years; 29.0% of drivers reported having used amphetamines within the twelve months prior to their interviews. After demographic and occupational variables had been controlled for, the factors which indicated amphetamine use among truck drivers were the following: being younger than 38 years (OR = 3.69, having spent less than nine years at school (OR = 1.76, being autonomous (OR = 1.65, working night shifts or irregular schedules (OR = 2.05, working over 12 hours daily (OR = 2.14, and drinking alcohol (OR = 1.74.CONCLUSIONS Occupational aspects are closely related to amphetamine use among truck drivers, which reinforces the importance of closely following the application of law (Resting Act (“Lei do Descanso”; Law 12,619/2012 which regulates the workload and hours of those professionals. Our results show the need for increased strictness on the trade and prescription of amphetamines in Brazil.

  1. 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.

  2. l-Amphetamine improves poor sustained attention while d-amphetamine reduces overactivity and impulsiveness as well as improves sustained attention in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD

    Directory of Open Access Journals (Sweden)

    Xu Tong

    2008-01-01

    Full Text Available Abstract Background 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. While dopamine release is decreased in SHR, norepinephrine concentrations are elevated. The primary objective of the present research was to test effects of a range of doses of the catecholamine agonists d- and l-amphetamine on ADHD-like symptoms in SHR. Methods The present study tested behavioral effects of 0.64 to 1.91 mg/kg d-amphetamine; and 1.27 to 3.81 mg/kg 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. Results The striking impulsiveness, overactivity, and poorer sustained attention during baseline conditions in the SHR were improved by treatment with the amphetamine isomers. The dose-response curves were, however, different for the different behaviors. Most significantly, d-amphetamine reduced overactivity and impulsiveness more efficiently than comparable doses of l-amphetamine. The lowest dose of d-amphetamine and low-to-medium doses of l-amphetamine improved sustained attention. The highest dose of d-amphetamine used interfered with SHR behavior. A second study showed that the impaired sustained attention (percent correct lever choice in the SHR was not due to impaired visual functions or poorer working memory. Discussion The present results indicate that

  3. The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine

    OpenAIRE

    Steinkellner, Thomas; Freissmuth, Michael; Sitte, Harald H; Montgomery, Therese

    2011-01-01

    Amphetamine (‘Speed’), methamphetamine (‘Ice’) and its congener 3,4-methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) are illicit drugs abused worldwide for their euphoric and stimulant effects. Despite compelling evidence for chronic MDMA neurotoxicity in animal models, the physiological consequences of such toxicity in humans remain unclear. In addition, distinct differences in the metabolism and pharmacokinetics of MDMA between species and different strains of animals prevent the rationalisa...

  4. The identification of an impurity product, 4,6-dimethyl-3,5-diphenylpyridin-2-one in an amphetamine importation seizure, a potential route specific by-product for amphetamine synthesized by the APAAN to P2P, Leuckart route.

    Science.gov (United States)

    Power, John D; O'Brien, John; Talbot, Brian; Barry, Michael; Kavanagh, Pierce

    2014-08-01

    During the analysis of a Customs' importation case for the suspected presence of controlled drugs, amphetamine was found to be present. The samples were also found to contain by-products from the amphetamine synthesis and these included benzyl cyanide, phenylacetone (P2P), methyl-phenyl-pyrimidines, N-formylamphetamine, a pair of naphthalene derivatives and amphetamine dimers. During the experimental investigation of the naphthalenes formation, a series of syntheses involved the acid hydrolysis of α-phenylacetoacetonitrile (APAAN). In one such experiment with sulfuric acid, a white substance was visibly deposited on the glassware and this was identified as the pyridone derivative, 4,6-dimethyl-3,5-diphenylpyridin-2-one. This compound was subsequently found to be present in the amphetamine product seized by the Customs and also in the final product of our own laboratory synthesized amphetamine (APAAN hydrolyzed to P2P/Leuckart reaction). Interestingly, the, 4,6-dimethyl-3,5-diphenylpyridin-2-one was not found when commercially supplied P2P underwent the Leuckart reaction to yield amphetamine. This suggests that 4,6-dimethyl-3,5-diphenylpyridin-2-one may be a route specific marker to the use of APAAN as a starting material in the synthesis of P2P and subsequent Leuckart reaction to yield amphetamine. PMID:24933633

  5. Determination of amphetamines in hair by integrating sample disruption, clean-up and solid phase derivatization.

    Science.gov (United States)

    Argente-García, A; Moliner-Martínez, Y; Campíns-Falcó, P; Verdú-Andrés, J; Herráez-Hernández, R

    2016-05-20

    The utility of matrix solid phase dispersion (MSPD) for the direct analysis of amphetamines in hair samples has been evaluated, using liquid chromatography (LC) with fluorescence detection and precolumn derivatization. The proposed approach is based on the employment of MSPD for matrix disruption and clean-up, followed by the derivatization of the analytes onto the dispersant-sample blend. The fluorogenic reagent 9-fluorenylmethyl chloroformate (FMOC) has been used for derivatization. Different conditions for MSPD, analyte purification and solid phase derivatization have been tested, using amphetamine (AMP), methamphetamine (MET), ephedrine (EPE) and 3,4-methylenedioxymethamphetamine (MDMA) as model compounds. The results have been compared with those achieved by using ultrasound-assisted alkaline digestion and by MSPD combined with conventional solution derivatization. On the basis of the results obtained, a methodology is proposed for the analysis of amphetamines in hair which integrates sample disruption, clean-up and derivatization using a C18 phase. Improved sensitivity is achieved with respect to that obtained by the alkaline digestion or by the MSPD followed by solution derivatization methods. The method can be used for the quantification of the tested amphetamines within the 2.0-20.0ng/mg concentration interval, with limits of detection (LODs) of 0.25-0.75ng/mg. The methodology is very simple and rapid (the preparation of the sample takes less than 15min). PMID:27108048

  6. Double resonance spectroscopy of different conformers of the neurotransmitter amphetamine and its clusters with water

    International Nuclear Information System (INIS)

    In this paper the conformational landscape of amphetamine in the neutral ground state is examined by both spectroscopy and theory. Several spectroscopic methods are used: laser-induced fluorescence (LIF), resonance-enhanced two-photon ionization (R2PI), dispersed fluorescence and IR/R2PI hole burning spectroscopy. The latter two methods provide for the first time vibrationally resolved spectra of the neutral ground state of dl-amphetamine and the amphetamine-(H2O)1,2 complexes. Nine stable conformers of the monomer were found by DFT (B3LYP/6-311++G(d,p)) and ab initio (MP2/6-311++G(d,p)) calculations. For conformer analysis the vibrations observed in the IR/R2PI hole burning and dispersed fluorescence spectra obtained from single vibronic levels (SVLF) of a selected conformer were compared with the results of an ab initio normal mode analysis. By this procedure three S0→ S1 transitions in the R2PI spectrum were assigned to three different conformer structures. Another weak transition earlier attributed to another conformer could be assigned to a vibronic band of one of the three conformers. Furthermore spectra of amphetamine-(H2O)1,2 are tentatively assigned

  7. 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 t...

  8. Simultaneous Determination of Heroin, Amphetamine and their Basic Impurities and Adulterants Using Microemulsion Electrokinetic Chromatography

    Institute of Scientific and Technical Information of China (English)

    Tao WEN; Xia ZHAO; Guo An LUO; Jian WANG; Yi Ming WANG; Pan LI; Jun ZHU; Zhong Shang YU

    2005-01-01

    Simultaneous separation of 17 species of heroin, amphetamine and their basic impurities and adulterants was conducted within 10 minutes by using capillary microemulsion electrokinetic chromatography. The influences of pH and 1-butanol cosurfactant on the separation were investigated, and 1-butanol was found to be a principal factor to improve separation efficiency.

  9. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Science.gov (United States)

    2010-04-01

    ... as prescription drugs. 250.101 Section 250.101 Food and Drugs FOOD AND DRUG ADMINISTRATION... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine... should not be freely available to the public through over-the-counter sale. From complaints by...

  10. Genetic NMDA receptor deficiency disrupts acute and chronic effects of cocaine but not amphetamine.

    Science.gov (United States)

    Ramsey, Amy J; Laakso, Aki; Cyr, Michel; Sotnikova, Tatyana D; Salahpour, Ali; Medvedev, Ivan O; Dykstra, Linda A; Gainetdinov, Raul R; Caron, Marc G

    2008-10-01

    NMDA receptor-mediated glutamate transmission is required for several forms of neuronal plasticity. Its role in the neuronal responses to addictive drugs is an ongoing subject of investigation. We report here that the acute locomotor-stimulating effect of cocaine is absent in NMDA receptor-deficient mice (NR1-KD). In contrast, their acute responses to amphetamine and to direct dopamine receptor agonists are not significantly altered. The striking attenuation of cocaine's acute effects is not likely explained by alterations in the dopaminergic system of NR1-KD mice, since most parameters of pre- and postsynaptic dopamine function are unchanged. Consistent with the behavioral findings, cocaine induces less c-Fos expression in the striatum of these mice, while amphetamine-induced c-Fos expression is intact. Furthermore, chronic cocaine-induced sensitization and conditioned place preference are attenuated and develop more slowly in mutant animals, but amphetamine's effects are not altered significantly. Our results highlight the importance of NMDA receptor-mediated glutamatergic transmission specifically in cocaine actions, and support a hypothesis that cocaine and amphetamine elicit their effects through differential actions on signaling pathways. PMID:18185498

  11. Reduced preabsorptive insulin response in aged rats : differential effects of amphetamine and arginine-vasopressin

    NARCIS (Netherlands)

    Buwalda, B.; Strubbe, J.H.; Bohus, B.

    1991-01-01

    The experiments presented here have been designed to investigate whether the age-related attenuation of the vagal reactivity to emotional stressors and its modulation by amphetamine (Amph) or arginine-vasopressin (AVP) can be generalized for other physiological response patterns. We therefore studie

  12. Methylphenidate and Amphetamine Do Not Induce Cytogenetic Damage in Lymphocytes of Children with ADHD

    Science.gov (United States)

    Witt, Kristine L.; Shelby, Michael D.; Itchon-Ramos, Nilda; Faircloth, Melissa; Kissling, Grace E.; Chrisman, Allan K.; Ravi, Hima; Murli, Hemalatha; Mattison, Donald R.; Kollins, Scott H.

    2008-01-01

    The inducement of chromosomal damage in lymphocytes among children with attention deficit hyperactivity disorder receiving treatment with methylphenidate- or amphetamine-based drugs is investigated. Findings did not reveal significant increases in cytogenetic damage related to the treatment. The risk for cytogenetic damage posed by such products…

  13. Effects of haloperidol and d-amphetamine on perceived quantity of food and tones.

    Science.gov (United States)

    Martin-Iverson, M T; Wilkie, D; Fibiger, H C

    1987-01-01

    The hypothesis that dopamine (DA) receptor agonists and antagonists affect "hedonia" associated with natural rewards was tested, using a psychophysical procedure previously shown to be sensitive to both the sweetness of food and the motivational state of rats. Rats were first trained to discriminate between two different quantities of a rewarding stimulus by pressing one of two levers. Perceived quantity was subsequently derived from generalization trials of intermediate quantities. Haloperidol (0.03-0.083 mg/kg), a DA receptor antagonist, did not influence perceived food quantity, an indirect marker of hedonic value. On the other hand, d-amphetamine (0.25-1.0 mg/kg) affected perceived food quantity in a dose-dependent fashion, and in the same direction as occurs after increasing hunger or food sweetness. Both haloperidol and amphetamine influenced the perceived quantity of a stimulus without natural reinforcing properties (a tone), but the effect of amphetamine on the perceived quantity of this initially neutral stimulus was opposite in direction to that observed with food. These results suggest that whereas amphetamine affects hedonic processes, haloperidol does not. In addition, it seems that haloperidol probably produces its actions through effects on motor mechanisms or by interfering with the response-facilitating properties of rewards. PMID:3124167

  14. Personality and gender differences in effects of d-amphetamine on risk taking.

    Science.gov (United States)

    White, Tara L; Lejuez, C W; de Wit, Harriet

    2007-12-01

    The effects of stimulant drugs on risk-taking behavior vary across individuals, even in healthy samples. These differences could relate to personality, which may share common mechanisms with drug effects or impulsive, risk-taking behavior. The current study investigated the role of temperament and gender in the effects of amphetamine on risk taking. Forty healthy men and women, aged 18 to 35, completed the Balloon Analogue Risk Task (BART; Lejuez et al., 2002) with three reward values after ingesting placebo or d-amphetamine (10, 20 mg). They completed the Multidimensional Personality Questionnaire Brief Form (MPQ-BF; Patrick et al., 2002), with three main scales: Trait reward sensitivity (Agentic Positive Emotionality; AgPEM), impulsivity (Constraint; CON), and negative affect (Negative Emotionality; NEM). d-Amphetamine (20 mg) decreased risk behavior in low AgPEM males, but increased risk behavior in high AgPEM males, producing positive correlations with AgPEM in men (r >or= +.55, pdrug did not affect risk-taking in women. There was evidence of discriminant validity between the AgPEM, NEM, and CON dimensions and behavioral responses to amphetamine. Implications for treatment and addiction are discussed. (c) 2008 APA, all rights reserved. PMID:18179313

  15. Effectiveness of Hope Therapy Protocol on Depression and Hope in Amphetamine Users

    Directory of Open Access Journals (Sweden)

    Sadeghi

    2015-12-01

    Full Text Available Background Addiction has surpassed the boundaries of health and treatment and turned into a social crisis and a debilitating and major concern in today’s world. Amphetamine, one of the addictive drugs, is classified as psycho-stimulants drugs, which increase arousal, alertness, and motor activity. Humans report that this drug produces a significant euphoria and is highly addictive. Objectives The present study aimed to evaluate the effectiveness of hope therapy protocol (HTP on depression reduction and hope increase in amphetamine users. Patients and Methods This study has a quasi-experimental design with experimental and control groups. The sample included all amphetamine consumers referring to day drug addiction treatment center in Ray City, Iran, selected with convenience method. In order to analyze the data, multivariate analysis of covariance (MANCOVA was applied using SPSS software. Results The results showed that F value of mean scores in depression and hope post-tests of the experimental and control groups are 24.94 and 25.73, respectively, which are significant (P < 0.01. Therefore, hope therapy training could reduce depressive symptoms in amphetamine consumers and improve their hope. Conclusions Performing HTP can improve hopefulness and symptoms of patients, specially addicted ones. In addition, it can prevent substance abusers from returning to drugs and leaving the treatment period unfinished.

  16. Medial prefrontal cortex infusions of bupivacaine or AP-5 block extinction of amphetamine conditioned place preference.

    Science.gov (United States)

    Hsu, Emily; Packard, Mark G

    2008-05-01

    The present experiments used reversible lesion techniques and intra-mPFC infusions of the n-methyl D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid (AP-5) to examine the role of the mPFC in extinction of an amphetamine conditioned place preference (CPP). Following initial training and testing for an amphetamine (2 mg/kg) CPP, adult male Long-Evans rats were given extinction trials that were identical to training, except in the absence of peripheral amphetamine injections. Immediately prior to each extinction trial, rats received intra-mPFC infusions of the anesthetic drug bupivacaine (0.75% solution/0.5 microl), AP-5 (1.25, 2.5, 5.0 microg/0.5 microl), or saline. Following extinction training, rats were given a second CPP test session. Rats receiving intra-mPFC infusions of saline displayed extinction of CPP behavior. In contrast, intra-mPFC infusions of bupivacaine or AP-5 (2.5, 5.0 microg) blocked CPP extinction. The findings indicate (1) the mPFC mediates extinction of approach behavior to drug-associated environmental contexts, and (2) NMDA receptor blockade within the mPFC is sufficient to block extinction of amphetamine CPP behavior. PMID:17905604

  17. 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...

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

    International Nuclear Information System (INIS)

    Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (370C) resulted in a time-dependent decrease in specific (+)-[3H]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 (+)-[3H]amphetamine binding, whereas incubations with L-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose failed to increase the number of (+)-[3H]amphetamine binding sites. Ouabain potently inhibited the glucose-induced stimulation of (+)-[3H]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 [3H]ouabain, and a good correlation was observed between the glucose-stimulated increase in (+)-[3H]amphetamine and [3H]ouabain binding. These data suggest that the (+)-[3H]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

  19. 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.

  20. 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

    2016-06-01

    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 [(11)C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [(11)C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [(11)C]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 [(11)C]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

  1. Amphetamine-related myocardial infarction in a 42-year old man.

    Science.gov (United States)

    Smędra, A; Szustowski, S; Berent, J

    2015-01-01

    Myocardial infarction is an infrequent condition in young adults. In most cases, it occurs due to causes other than atherosclerosis of the coronary arteries, including blood hypercoagulability, congenital anomalies of the coronary arteries, their inflammation or spasm induced by amphetamine or cocaine use. Amphetamine and its derivatives, via increasing the levels of epinephrine, serotonin and dopamine in the central nervous system, exert their effect also on the cardiovascular system, causing coronary spasm, enhancing platelet aggregation and inducing tachyarrhythmias. The paper presents a case of a 42-year-old man admitted to the emergency department because of emaciation and dehydration. The man was conscious, without contact, with a significant elevation of body temperature and tachycardia. On the basis of examinations, a fresh infarction of the anterolateral wall of the heart was diagnosed and the patient was transferred to a cardiac intensive care unit. There, laboratory tests revealed significantly elevated markers of myocardial necrosis and the presence of amphetamine in blood and urine. In spite of the institution of treatment the patient developed cardiorespiratory arrest. Advanced resuscitation procedures were undertaken, however, they proved unsuccessful. The presence of an infarction focus was confirmed in autopsy. Toxicological analysis of the blood for the presence of alcohol-like substances detected amphetamine at a concentration of 269.5 ng/ml. After examining the complete body of evidence it was established that the patient had died of acute cardiorespiratory failure secondary to an extensive fresh myocardial infarction. As indicated by the accumulated data, the most probable cause of myocardial infarction was amphetamine poisoning. PMID:27003867

  2. Trends of Amphetamine Type Stimulants DTR Mass Load in Poznan Based on Wastewater Analysis.

    Directory of Open Access Journals (Sweden)

    Piotr Nowicki

    2014-05-01

    Full Text Available The aim of this study was to determine the monthly DTR mass load of amphetamine-type compounds in Poland as well as an investigation of cyclical behaviour by using time series analysis and especially trends analysis.Amphetamine, methamphetamine and MDMA (ecstasy were detected in wastewater samples collected from the main Wastewater Treatment Plant in the city of Poznan using liquid chromatography / tandem mass spectrometry (LC-MS-MS. Back-calculations used in the sewage epidemiology approach were applied to estimate the DTR mass load level of the drugs analyzed. Trends analysis was performed by fitting the data to a simple linear regression and then by using smoothing by means of a moving average (Mat lab 2013a. Trend analysis displays a steady tendency of increase or decrease throughout time series. When we plot the observation against time, we may notice that a straight line can describe the increase or decrease in the series as time goes on. Simple linear regression and method of last squares to estimate parameters of a straight-line model were used. Additionally, a lagged plot (autocorrelation plot was used to investigate an appearance of correlation between amphetamines throughout time.Trends analysis showed the slight increase in consumption of amphetamine and decreasing trend in case of ecstasy and methamphetamine within the investigated period. There is also visible, strong correlation between ecstasy and methamphetamine consumption which cannot be stated in case of amphetamine.Trends analysis is a very useful tool to analyse the increasing or decreasing tendency in consumption of illicit drugs based on the DTR mass load data.

  3. Multiresidual analysis of emerging amphetamine-like psychoactive substances in wastewater and river water.

    Science.gov (United States)

    Senta, Ivan; Krizman, Ivona; Ahel, Marijan; Terzic, Senka

    2015-12-18

    Besides the common illicit drugs, such as cocaine, heroin, and marijuana, there is a growing concern about the use of modern "designer drugs" that have emerged in large numbers over the past few years. In this work, a sensitive and selective method for simultaneous determination of 25 synthetic amphetamine-like psychoactive compounds, including amphetamine, sympathomimetic substituted amphetamines, synthetic cathinones and ketamine, in raw wastewater (RW), secondary effluent (SE) and river water was developed. Samples were enriched by solid-phase extraction (SPE) on mixed-mode reversed-phase/strong cation-exchange sorbent (Oasis MCX) and analysed by reversed-phase liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (LC-MS/MS). The target compounds were separated on a Synergi Polar column and detected using multiple reaction monitoring (MRM) in positive ionisation mode. Accurate quantification was achieved by using several deuterated analogues as surrogate standards. Careful optimisation and validation of the procedure resulted in a reliable determination of all target analytes in low ng/L range for all matrices, which makes the method suitable for the application in wastewater-based epidemiology. The method was applied for assessment of selected compounds in municipal wastewater and river water from Croatia. It was shown that most of the wastewater samples contained detectable levels of the well-known synthetic illicit drugs, amphetamine and 3,4-methylenedioxy-methamphetamine (MDMA) (concentrations up to 545ng/L and 55ng/L in RW, respectively), as well as ephedrine (up to 108ng/L) and pseudoephedrine (up to 698ng/L), which are used as ingredients of popular over-the counter cough and cold medications. Other target amphetamine-like psychoactive substances, recently reported for their potential abuse, were detected only occasionally and in low concentrations (<10ng/L). PMID:26607313

  4. Serotonergic responses to stress are enhanced in the central amygdala and inhibited in the ventral hippocampus during amphetamine withdrawal

    OpenAIRE

    Li, Hao; Scholl, Jamie L.; Tu, Wenyu; Hassell, James; Watt, Michael J.; Forster, Gina L.; Renner, Kenneth J.

    2014-01-01

    Withdrawal from amphetamine increases anxiety and reduces the ability to cope with stress, factors that are believed to contribute to drug relapse. Stress-induced serotonergic transmission in the central nucleus of the amygdala is associated with anxiety states and fear. Conversely, increases in stress-induced ventral hippocampal serotonin have been linked to coping mechanisms. The goal of this study is to understand neurobiological changes induced by amphetamine that contribute to stress-sen...

  5. Surveillance of Diversion and Nonmedical Use of Extended-Release Prescription Amphetamine and Oral Methylphenidate in the United States

    OpenAIRE

    Sembower, Mark A.; Ertischek, Michelle D.; Buchholtz, Chloe; Dasgupta, Nabarun; Schnoll, Sidney H.

    2013-01-01

    This article examines rates of nonmedical use and diversion of extended-release amphetamine and extended-release oral methylphenidate in the United States. Prescription dispensing data were sourced from retail pharmacies. Nonmedical use data were collected from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Drug Diversion Program and Poison Center Program. Drug diversion trends nearly overlapped for extended-release amphetamine and extended-release oral met...

  6. Behavioral effects of prenatal d-amphetamine in rats: a parallel trial to the Collaborative Behavioral Teratology Study.

    Science.gov (United States)

    Vorhees, C V

    1985-01-01

    Pregnant Sprague-Dawley rats treated with 0, 0.5 or 2.0 mg/kg of d-amphetamine sulphate on days 12-15 of gestation or left untreated as part of the NCTR Collaborative Behavioral Teratology Study were assigned to either the Collaborative Study or Cincinnati Test protocol after birth. Offspring assigned to the Cincinnati test system were evaluated for growth, mortality, incisor eruption, eye opening, vaginal patency, surface righting, negative geotaxis, pivoting, auditory startle, olfactory orientation, swimming ontogeny, figure-8 activity, and complex water maze (Biel) problem solving. Amphetamine at both doses caused fewer offspring to be born per litter and reduced the proportion of males born in the 0.5 mg/kg group. Amphetamine produced no reliable effects on offspring growth as reflected by weight or survival. The 0.5 mg/kg amphetamine group showed delayed eye opening, but the 2.0 mg/kg group did not. Amphetamine produced no significant effects on other physical landmarks of development or on measures of behavioral performance except swimming ontogeny. Early swimming direction scores were significantly lower in the amphetamine groups compared to controls, but the effect was isolated; no other aspect of swimming was affected. It was concluded that at the doses and exposure period used here, d-amphetamine appears to be at best weakly behaviorally teratogenic using the Cincinnati test system. This finding is in general agreement with the results obtained with the same treatment regiment in the NCTR Collaborative Study. Both test systems appear comparable at correctly identifying the low level of behavioral teratogenicity of moderate doses of prenatal d-amphetamine. PMID:3835471

  7. 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.

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

    Science.gov (United States)

    Al Shehri, Mohammed A; Youssef, Ali A

    2016-07-01

    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. PMID:27358538

  9. Differential Influence of Dopamine Transport Rate on the Potencies of Cocaine, Amphetamine, and Methylphenidate

    OpenAIRE

    Calipari, Erin S.; Ferris, Mark J.; Siciliano, Cody A.; JONES, SARA R.

    2014-01-01

    Dopamine transporter (DAT) levels vary across brain regions and individuals, and are altered by drug history and disease states; however, the impact of altered DAT expression on psychostimulant effects in brain has not been systematically explored. Using fast scan cyclic voltammetry, we measured the effects of elevated DAT levels on presynaptic dopamine parameters as well as the uptake inhibition potency of the blockers cocaine and methylphenidate (MPH) and the releaser amphetamine (AMPH) in ...

  10. 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.

  11. Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

    OpenAIRE

    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

    2014-01-01

    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 [11C]raclopride PET with a d-amphetamine chal...

  12. 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. PMID:22005052

  13. ANTIPSYCHOTIC ACTIVITY OF AQUEOUS ETHANOLIC EXTRACT OF TINOSPORA CORDIFOLIA IN AMPHETAMINE CHALLENGED MICE MODEL

    OpenAIRE

    Abhilasha Shete; Vibhor Kumar Jain; Bindu nee Giri Jain

    2010-01-01

    Tinospora cordifolia is reported to have CNS active principle and is used for thetreatment of various neurological disorders. Hence, the effect of aqueous ethanolicextract of Tinospora cordifolia was investigated for its putative antipsychotic activityusing amphetamine challenged mice model. Haloperidol (1 mg/kg i.p.) was administeredacutely to mice as standard drug. Control animals received vehicle (10% DMSO). The invivo receptor binding studies were carried out to correlate the antipsychoti...

  14. ANTIPSYCHOTIC ACTIVITY OF AQUEOUS ETHANOLIC EXTRACT OF TINOSPORA CORDIFOLIA IN AMPHETAMINE CHALLENGED MICE MODEL

    OpenAIRE

    Bindu nee Giri Jain; Vibhor Kumar Jain; Abhilasha Shete

    2010-01-01

    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 antipsy...

  15. Stereoselective accumulation of hydroxylated metabolites of amphetamine in rat striatum and hypothalamus.

    OpenAIRE

    Dougan, D. F.; Duffield, A. M.; Duffield, P. H.; Wade, D. N.

    1986-01-01

    The stereoselective accumulation of alpha-methyl-p-tyramine (AMPT) and alpha-methyl-p-octopamine (AMPO) in rat striatum and hypothalamus after acute and chronic administration of the (+)- and (-)-isomers of amphetamine (Amphet) and the acute administration of (+)- and (-)-AMPT has been investigated by chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.). Two h after the administration of (+)- or (-)-AMPT (5 mg kg-1 i.p.), the concentrations of the isomers in striatal tissue...

  16. Performance and subjective effects of diazepam and d-amphetamine in high and low sensation seekers

    OpenAIRE

    Kelly, Thomas H.; Delzer, Timothy A.; Martin, Catherine A.; Harrington, Nancy G.; Hays, Lon R.; Bardo, Michael T.

    2009-01-01

    Although sensation-seeking status is associated with age of initiation and amount of drug use among adolescents, and sensitivity to the behavioral and reinforcing effects of drugs among young adults, it is unclear whether sensation-seeking status among adolescents is predictive of sensitivity to the pharmacological effects of drugs (i.e. abuse potential) as adults. This study examined the acute behavioral effects of oral diazepam and d-amphetamine in young adults, ages 18–21 years, who had co...

  17. 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.

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

    OpenAIRE

    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 potential of a single exposure to stress is not clear. Both drug- and stress-induced sensitization depend on an enhanced dopaminergic neurotransmission in the mesolimbic DA system. Apart from respon...

  19. Genetic variants in the cocaine- and amphetamine-regulated transcript gene (CARTPT) and cocaine dependence

    OpenAIRE

    Lohoff, Falk W.; Bloch, Paul J.; Weller, Andrew E.; Nall, Aleksandra H.; Doyle, Glenn A.; Buono, Russell J.; Ferraro, Thomas N.; Kampman, Kyle M.; Pettinati, Helen M.; Dackis, Charles A.; Oslin, David W.; O'Brien, Charles P.; BERRETTINI, WADE H.

    2008-01-01

    Dopaminergic brain systems have been implicated to play a major role in drug reward, thus making genes involved in these circuits plausible candidates for susceptibility to substance use disorders. The cocaine- and amphetamine-regulated transcript peptide (CARTPT) is involved in reward and feeding behavior and has functional characteristics of an endogenous psychostimulant. In this study we tested the hypothesis that variation in the CARTPT gene increases susceptibility to cocaine dependence ...

  20. The Development of Context-specific Operant Sensitization to d-Amphetamine

    OpenAIRE

    Thomas, Wesley Paul

    2009-01-01

    Animal models have previously been used to study tolerance and sensitization using two different procedures that are difficult to compare. Tolerance has been studied by administering a drug to a subject that is engaged in an operant behavior, and sensitization by administering a drug to a subject that is not engaged in an operant behavior. Previous research has shown that sensitization can occur when d-amphetamine is administered to rats emitting an operant behavior for a food presentation. T...

  1. The Effects of Progesterone Pretreatment on the Response to Oral d-Amphetamine in Women

    OpenAIRE

    Reed, Stephanie C.; Levin, Frances R.; Evans, Suzette M.

    2010-01-01

    Stimulant abuse continues to be a problem, particularly for women. There is increasing preclinical and clinical evidence showing that the hormone progesterone attenuates the behavioral effects of cocaine, and this effect is primarily observed in females. The purpose of the present study was to determine if progesterone would also alter the behavioral effects of another stimulant, oral d-amphetamine (AMPH) in women. Eighteen normal non-drug abusing women completed eight outpatient sessions ove...

  2. Adolescent social defeat increases adult amphetamine conditioned place preference and alters D2 dopamine receptor expression

    OpenAIRE

    Burke, Andrew R.; Watt, Michael J.; Forster, Gina L.

    2011-01-01

    Components of the brain’s dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. Rats exposed to repeated social defeat in adolescence (P35–P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70). In co...

  3. Associations Between Cocaine, Amphetamine or Psychedelic Use and Psychotic Symptoms in a Community Sample

    OpenAIRE

    Kuzenko, Nina; Sareen, Jitender; Beesdo-Baum, Katja; Perkonigg, Axel; Höfler, Michael; Simm, James; Lieb, Roselind; Wittchen, Hans-Ulrich

    2013-01-01

    Objective: To investigate whether there is an association between use of cocaine, amphetamines, or psychedelics and psychotic symptoms. Method: Cumulated data from a prospective, longitudinal community study of 2588 adolescents and young adults in Munich, Germany were used. Substance use was assessed at baseline, 4-year and 10-year follow-up using the Munich Composite International Diagnostic Interview; psychotic symptoms were assessed at 4-year and 10-year follow-up. Multinomial logist...

  4. Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine

    Directory of Open Access Journals (Sweden)

    Michael Pennick

    2010-06-01

    Full Text Available Michael PennickBiosciences Department, Shire Pharmaceutical Development Ltd, Basingstoke, UKAbstract: These studies investigated the absorption and metabolic conversion of lisdexamfetamine dimesylate (LDX, a prodrug stimulant that requires conversion to d-amphetamine for activity. Oral absorption of LDX was assessed in rat portal and jugular blood, and perfusion of LDX into isolated intestinal segments of anesthetized rats was used to assess regional absorption. Carrier-mediated transport of LDX was investigated in Caco-2 cells and Chinese hamster ovary (CHO cells expressing human peptide transporter-1 (PEPT1. LDX metabolism was studied in rat and human tissue homogenates and human blood fractions. LDX was approximately10-fold higher in portal blood versus systemic blood. LDX and d-amphetamine were detected in blood following perfusion of the rat small intestine but not the colon. Transport of LDX in Caco-2 cells had permeability apparently similar to cephalexin and was reduced with concurrent PEPT1 inhibitor. Affinity for PEPT1 was also demonstrated in PEPT1-transfected CHO cells. LDX metabolism occurred primarily in whole blood (rat and human, only with red blood cells. Slow hydrolysis in liver and kidney homogenates was probably due to residual blood. The carrier-mediated absorption of intact LDX, likely by the high-capacity PEPT1 transporter, and subsequent metabolism to d-amphetamine in a high-capacity system in blood (ie, red blood cells may contribute to the consistent, reproducible pharmacokinetic profile of LDX.Keywords: lisdexamfetamine dimesylate, LDX, prodrug, ADHD, absorption, Vyvanse

  5. Performance enhancing, non-prescription use of Ritalin: a comparison with amphetamines and cocaine.

    Science.gov (United States)

    Svetlov, Stanislay I; Kobeissy, Firas H; Gold, Mark S

    2007-01-01

    Ritalin, known under chemical name methylphenidate (MPH), is a psychostimulant prescribed to treat attention-deficit/hyperactivity disorder (ADHD) and other conditions. Psychotropic effects and pharmacological pathways evoked by MPH are similar, but not identical to those produced by amphetamines and cocaine. Although not completely understood in detail, MPH psychostimulation is mediated by the increase of central dopamine (DA) and possibly norepinephrine (NE) and serotonin (ST) due to decrease of their re-uptake via binding to and inhibition of DA, NE, and ST transporters. Despite similarity in psychopharmacological effects, the rewarding/ reinforcing ability of MPH appears to be significantly lower than amphetamines and especially cocaine. MPH and similar medications have been widely used on College campuses and by students preparing for exams. Nicknamed 'steroids for SATs,' MPH and related medications are purchased without prescription and their use may even be encouraged by parents and tutors. However, while widely and safely used and administered for over forty years, Ritalin generated significant controversy including MPH abuse and addiction, and adverse reactions. It is now clear that treatment of ADD/ADHD with psychostimulants prevents drug abuse and addictions. Use by those without any medical or psychiatric diagnosis is increasing. In this mini-review, we discuss psychopharmacological and behavioral aspects, and outline neurochemical mechanisms that may provoke Ritalin abuse, addiction and adverse effects compared to amphetamines and cocaine. PMID:18032226

  6. Improvement in measures of psychological distress amongst amphetamine misusers treated with brief cognitive-behavioural therapy (CBT).

    Science.gov (United States)

    Feeney, G F X; Connor, J P; Young, R McD; Tucker, J; McPherson, A

    2006-10-01

    This trial of cognitive-behavioural therapy (CBT) based amphetamine abstinence program (n=507) focused on refusal self-efficacy, improved coping, improved problem solving and planning for relapse prevention. Measures included the Severity of Dependence Scale (SDS), the General Health Questionnaire-28 (GHQ-28) and Amphetamine Refusal Self-Efficacy. Psychiatric case identification (caseness) across the four GHQ-28 sub-scales was compared with Australian normative data. Almost 90% were amphetamine-dependent (SDS 8.15+/-3.17). Pre-treatment, all GHQ-28 sub-scale measures were below reported Australian population values. Caseness was substantially higher than Australian normative values {Somatic Symptoms (52.3%), Anxiety (68%), Social Dysfunction (46.5%) and Depression (33.7%)}. One hundred and sixty-eight subjects (33%) completed and reported program abstinence. Program completers reported improvement across all GHQ-28 sub-scales {Somatic Symptoms (p<0.001), Anxiety (p<0.001), Social Dysfunction (p<0.001) and Depression (p<0.001)}. They also reported improvement in amphetamine refusal self-efficacy (p<0.001). Improvement remained significant following intention-to-treat analyses, imputing baseline data for subjects that withdrew from the program. The GHQ-28 sub-scales, Amphetamine Refusal Self-Efficacy Questionnaire and the SDS successfully predicted treatment compliance through a discriminant analysis function (p<.001). PMID:16431030

  7. The time-dependent and persistent effects of amphetamine treatment upon recovery from hemispatial neglect in rats.

    Science.gov (United States)

    Brenneman, Miranda M; Hylin, Michael J; Corwin, James V

    2015-10-15

    Neglect is a neuropsychological disorder characterized by the failure to report or respond to stimuli presented to the side of the body opposite a brain lesion and occurs in approximately 40% of right hemisphere strokes. The need for effective therapies to treat neglect in humans has led to the development of a rodent model. Unilateral destruction of medial agranular cortex (AGm), which is part of a cortical network for directed attention, produces severe multimodal neglect with deficits similar to those seen in humans. Amphetamines have previously been investigated for inducing plasticity and recovery of function following brain damage. Amphetamine treatment has been shown to produce recovery from visual, frontal, and sensorimotor cortex damage in animals and this recovery may be the result of axonal growth originating from the opposite, unlesioned hemisphere. The purpose of this study was to investigate whether amphetamine treatment would induce recovery from neglect produced by unilateral AGm destruction, the time frame in which amphetamine must be administered in order to be effective, and the permanence of recovery following treatment. The results indicated that subjects injected with 2mg/kg of d-amphetamine on days 0, 2, and 5 recovered in significantly fewer days than saline-treated controls, even when administration was delayed by 2 and 7 days. Additionally, these studies indicated that recovery persisted for at least 60 days suggesting that recovery is likely to be long term. PMID:26209293

  8. The dopamine D1-D2 receptor heteromer exerts tonic inhibitory effect on the expression of amphetamine-induced locomotor sensitization

    Science.gov (United States)

    Shen, Maurice Y.F.; Perreault, Melissa L.; Fan, Theresa; George, Susan R.

    2014-01-01

    A role for the dopamine D1-D2 receptor heteromer in the regulation of reward and addiction-related processes has been previously implicated. In the present study, we examined the effects of D1-D2 heteromer stimulation by the agonist SKF 83959 and its disruption by a selective TAT-D1 peptide on amphetamine-induced locomotor sensitization, a behavioural model widely used to study the neuroadaptations associated with psychostimulant addiction. D1-D2 heteromer activation by SKF 83959 did not alter the acute locomotor effects of amphetamine but significantly inhibited amphetamine-induced locomotor responding across the 5 day treatment regimen. In addition, a single injection of SKF 83959 was sufficient to abolish the expression of locomotor sensitization induced by a priming injection of amphetamine after a 72-hour withdrawal. Conversely, inhibition of D1-D2 heteromer activity by the TAT-D1 peptide enhanced subchronic amphetamine-induced locomotion and the expression of amphetamine locomotor sensitization. Treatment solely with the TAT-D1 disrupting peptide during the initial 5 day treatment phase was sufficient to induce a sensitized locomotor phenotype in response to the priming injection of amphetamine. Together these findings demonstrate that the dopamine D1-D2 receptor heteromer exerts tonic inhibitory control on neurobiological processes involved in sensitization to amphetamine, indicating that the dopamine D1-D2 receptor heteromer may be a novel molecular substrate in addiction processes involving psychostimulants. PMID:25444866

  9. 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

    and anxiety disorders. In addition, SERT is a major molecular target for psychostimulants such as cocaine and amphetamines. Amphetamine-induced transport reversal at the closely related dopamine transporter (DAT) has been shown previously to be contingent upon modulation by calmodulin kinase IIα (α......CaMKII was verified using biochemical assays and FRET analysis and colocalization of the two molecules was confirmed in primary serotonergic neurons in culture. Moreover, we found that genetic deletion of αCaMKII impaired the locomotor response of mice to 3,4-methylenedioxymethamphetamine (also known as "ecstasy......") and blunted d-fenfluramine-induced prolactin release, substantiating the importance of αCaMKII modulation for amphetamine action at SERT in vivo as well. SERT-mediated substrate uptake was neither affected by inhibition of nor genetic deficiency in αCaMKII. This finding supports the concept that uptake...

  10. 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

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

    DEFF Research Database (Denmark)

    Lind, Nanna Marie; Arnfred, Sidse M; Hemmingsen, Ralf 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...... validation of a pig model of psychosis, we wished to verify the existence of PPI in landrace pigs and investigate the potential disruption of PPI by d-amphetamine (AMPH) in these animals. PPI of the acoustic startle reflex and its potential disruption by AMPH were investigated using three doses 0.5-1.5mg...... valuable additional tool in assessing pig models of neuropsychiatric disorders....

  12. Cerebral radionuclide tomography using 123I-isopropyl-amphetamine in cerebral ischaemic pathology

    International Nuclear Information System (INIS)

    Thirty patients with previous cerebral ischaemic accident were explored by both computerized tomography (CT) and radionuclide tomography after injection of 123I-labeled N-isopropyl-iodo-amphetamine. All lesions that were visible at CT were also visible at radionuclide tomography. However, in 7 patients with normal CT results the latter method showed areas of cerebral activity anatomically correlated with neurological signs or vascular lesions. Cerebellar diaschisis was observed in 50% of established lesions in the carotid territory. Radionuclide tomography therefore appears as a very sensitive method to be used in ischaemic pathology with transient or regressive accidents

  13. The quantitation of N-isopropyl-p-I-123 amphetamine cerebral perfusion and function studies

    International Nuclear Information System (INIS)

    A method of quantitatively analyzing ECT sections obtained from cerebral perfusion/function studies with N-isopropyl-p-I-123 Amphetamine (IMP) is presented and illustrated by a concrete case. This analysis makes use of six pairs of regions delineating the perfusion territories of the major cerebral arteries, and produces six right-left ratios which provide objective criteria to assess pathology and, in our opinion, is an important adjunct to visual interpretation of IMP studies. Even though quantitation of rCBF with IMP is highly desirable, no satisfactory method short of arterial input sampling seems to have been used so far to obtain absolute blood flow values. (orig.)

  14. Serotonergic responses to stress are enhanced in the central amygdala and inhibited in the ventral hippocampus during amphetamine withdrawal.

    Science.gov (United States)

    Li, Hao; Scholl, Jamie L; Tu, Wenyu; Hassell, James E; Watt, Michael J; Forster, Gina L; Renner, Kenneth J

    2014-12-01

    Withdrawal from amphetamine increases anxiety and reduces the ability to cope with stress, which are factors that are believed to contribute to drug relapse. Stress-induced serotonergic transmission in the central nucleus of the amygdala is associated with anxiety states and fear. Conversely, stress-induced increases in ventral hippocampal serotonin (5-HT) levels have been linked to coping mechanisms. The goal of this study was to investigate the neurobiological changes induced by amphetamine that contribute to stress sensitivity during withdrawal. We tested the hypothesis that limbic serotonergic responses to restraint stress would be altered in male Sprague-Dawley rats chronically pretreated with amphetamine (2.5 mg/kg, intraperitoneal) and then subjected to 2 weeks of withdrawal. Amphetamine withdrawal resulted in increased stress-induced behavioral arousal relative to control treatment, suggesting that drug withdrawal induced greater sensitivity to the stressor. When microdialysis was used to determine the effects of restraint on extracellular 5-HT, stress-induced increases in 5-HT levels were abolished in the ventral hippocampus and augmented in the central amygdala during amphetamine withdrawal. Reverse dialysis of the glucocorticoid receptor antagonist mifepristone into the ventral hippocampus blocked the stress-induced increase in 5-HT levels in saline-pretreated rats, suggesting that glucocorticoid receptors mediate stress-induced increases in 5-HT levels in the ventral hippocampus. However, mifepristone had no effect on stress-induced increases in 5-HT levels in the central amygdala, indicating that stress increases 5-HT levels in this region independently of glucocorticoid receptors. During amphetamine withdrawal, the absence of stress-induced increases in ventral hippocampal 5-HT levels combined with enhanced stress-induced serotonergic responses in the central amygdala may contribute to drug relapse by decreasing stress-coping ability and heightening

  15. 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

    The aim of the present study was to investigate the composition of heroin, amphetamine, and cocaine seized in the police district of Aarhus, the second largest city in Denmark, during a 2-year period. The purity of the active substance was measured together with the frequency and purity 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" of...

  16. 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...... response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT N terminus and mediates amphetamine-induced dopamine efflux....

  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...... response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT N terminus and mediates amphetamine-induced dopamine efflux....

  18. Alterations in subcellular expression of acid-sensing ion channels in the rat forebrain following chronic amphetamine administration

    OpenAIRE

    Suman, Ajay; Mehta, Bhavi; Guo, Ming-Lei; Chu, Xiang-Ping; Fibuch, Eugene E.; Mao, Li-Min; WANG, John Q.

    2010-01-01

    Acid-sensing ion channels (ASICs) are densely expressed in broad areas of mammalian brains and actively modulate synaptic transmission and a variety of neuronal activities. To explore whether ASICs are linked to addictive properties of drugs of abuse, we investigated the effect of the psychostimulant amphetamine on subcellular ASIC expression in the rat forebrain in vivo. Repeated administration of amphetamine (once daily for 7 days, 1.25 mg/kg for days 1/7, 4 mg/kg for days 2–6) induced typi...

  19. Development of a harmonized method for the profiling of amphetamines. I. Synthesis of standards and compilation of analytical data.

    Science.gov (United States)

    Aalberg, Laura; Andersson, Kjell; Bertler, Christina; Borén, Hans; Cole, Michael D; Dahlén, Johan; Finnon, Yvonne; Huizer, Henk; Jalava, Kaisa; Kaa, Elisabet; Lock, Eric; Lopes, Alvaro; Poortman-van der Meer, Anneke; Sippola, Erkki

    2005-05-10

    Reference material was synthesised for 21 substances that are frequently present as synthetic impurities, i.e. by-products, in illicitly produced amphetamine. Each of these substances is a typical by-product for at least one of the three approaches most often used to synthesise amphetamine, namely, the Leuckart, the reductive amination of benzyl methyl ketone, and the nitrostyrene routes. A large body of data on the substances was recorded, including the following: mass spectra, ultraviolet spectra, Fourier transform infrared spectra, infrared spectra in gas phase, and 1H NMR and 13C NMR spectra. PMID:15749364

  20. 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.

  1. Recent topics on pharmacotherapy for amphetamine-type stimulants abuse and dependence.

    Science.gov (United States)

    Chen, Hongxian; Wu, Jin; Zhang, Jichun; Hashimoto, Kenji

    2010-12-01

    Abuse of amphetamine-type stimulants (ATS), including amphetamine, methamphetamine (METH), and 3,4-methylenedioxymethamphetamine (MDMA; ecstasy), has become a major public health problem worldwide. Use of these stimulants has significant psychiatric and medical consequences, including psychosis, dependence, overdose, and death. METH abuse in particular is an extremely serious and growing problem in many countries. The development of treatments for METH-related problems is particularly critical for users who experience persistent psychosis, pregnant women and women with children, gay and bisexual men, and users involved in the criminal justice system. However, there are currently no pharmacological treatments for the wide range of symptoms associated with METH-related problems. One of the reasons for this problem is that our knowledge of the cellular and molecular mechanisms underlying the development of METH-induced psychosis and dependence is limited. In this article, we review recent reports on potential pharmacotherapies (naltrexone, minocycline, antioxidants, immunotherapy, and dopaminergic, serotonergic, cholinergic, and GABAergic agents) for the treatment of ATS abusers. PMID:21208168

  2. 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.

  3. Brain SPECT with /sup 123/I-labelled amphetamine derivatives in epilepsy and migraine

    International Nuclear Information System (INIS)

    On the basis of positron tomography (PET) results it has been well established that seizures are connected with increases in regional cerebral blood flow and metabolism. In the interictal stage, however, regionally diminished perfusion can be observed in the affected cortical areas. As changes in cerebral function due to seizures are seldom accompanied by structural changes they often cannot be detected by radiographic techniques. Here the EEG is useful, but has significant limitations: It is often difficult to lateralize or localize the origin of the seizure or to assess the severity and extent of underlying cerebral involvement. Since 1982 SPECT with /sup 123/I-labelled N-isopropyl amphetamines (IMP) has been used for the evaluation of epilepsy. By means of this technique, identical findings - ictally increased, interictally decreased tracer accumulation - as with PET were established. In addition, amphetamine SPECT can reveal increased perfusion in epileptic foci at a time when there is focal electrical discharge, even in the absence of clinically recognizable seizures. The present paper presents an overview of the authors' results in a relatively large series of patients with epilepsy. Data are also included of patients with migraine accompagnee - a disease in which EEG pathology may also be observed

  4. Heroin and amphetamine users display opposite relationships between trait and neurobehavioral dimensions of impulsivity.

    Science.gov (United States)

    Vassileva, Jasmin; Paxton, Jessica; Moeller, F Gerard; Wilson, Michael J; Bozgunov, Kiril; Martin, Eileen M; Gonzalez, Raul; Vasilev, Georgi

    2014-03-01

    The multidimensional construct of impulsivity is implicated in all phases of the addiction cycle. Substance dependent individuals (SDIs) demonstrate elevated impulsivity on both trait and laboratory tests of neurobehavioral impulsivity; however our understanding of the relationship between these different aspects of impulsivity in users of different classes of drugs remains rudimentary. The goal of this study was to assess for commonalities and differences in the relationships between trait and neurobehavioral impulsivity in heroin and amphetamine addicts. Participants included 58 amphetamine dependent (ADIs) and 74 heroin dependent individuals (HDIs) in protracted abstinence. We conducted Principal Component Analyses (PCA) on two self-report trait and six neurobehavioral measures of impulsivity, which resulted in two trait impulsivity (action, planning) and four neurobehavioral impulsivity composites (discriminability, response inhibition efficiency, decision-making efficiency, quality of decision-making). Multiple regression analyses were used to determine whether neurobehavioral impulsivity is predicted by trait impulsivity and drug type. The analyses revealed a significant interaction between drug type and trait action impulsivity on response inhibition efficiency, which showed opposite relationships for ADIs and HDIs. Specifically, increased trait action impulsivity was associated with worse response inhibition efficiency in ADIs, but with better efficiency in HDIs. These results challenge the unitary account of drug addiction and contribute to a growing body of literature that reveals important behavioral, cognitive, and neurobiological differences between users of different classes of drugs. PMID:24342174

  5. Personality and the acute subjective effects of d-amphetamine in humans.

    Science.gov (United States)

    Kirkpatrick, Matthew G; Johanson, Chris-Ellyn; de Wit, Harriet

    2013-03-01

    There is evidence that subjective responses to psychoactive drugs are related to personality traits. Here, we extend previous findings by examining personality measures in relation to acute responses to d-amphetamine (AMPH) in a large sample of healthy volunteers. Healthy adults (n=286) completed the Multidimensional Personality Questionnaire Brief Form (MPQ-BF) and participated in four sessions during which they received oral AMPH (0, 5, 10, 20 mg), under double-blind conditions. Subjective responses to the drug were measured using the Profile of Mood States, Addiction Research Center Inventory, and Drug Effects Questionnaire. Drug responses were reduced via principal components analysis to three higher-order factors ('Euphoria', 'Arousal', 'Dysphoria'). Participants were rank ordered on selected MPQ-BF scales; the top and bottom third on each trait were compared on the drug response factors. High trait physical fearlessness was significantly associated with greater amphetamine-related Arousal, and high trait reward sensitivity was significantly associated with greater Euphoria. In addition, high trait impulsivity was significantly associated with greater Arousal and Euphoria. These results provide further evidence that individual differences in the subjective effects of AMPH are partially explained by differences in personality, and are consistent with the idea that both personality and responses to stimulants depend upon shared neurochemical systems. PMID:23343596

  6. 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. PMID:25563230

  7. Chronic treatment with mood stabilizer lithium inhibits amphetamine-induced risk-taking manic-like behaviors.

    Science.gov (United States)

    Zhou, Zhu; Wang, Ying; Tan, Hua; Bharti, Veni; Che, Yi; Wang, Jun-Feng

    2015-08-31

    A lack of behavioral tests and animal models for manic-depressive bipolar disorder is recognized as an important factor limiting development of novel pharmaceutical treatments for the disorder. Repeated amphetamine-induced hyperactivity is a commonly used animal model for mania. However, hyperactivity represents only one facet of mania and is also seen in other disorders. Increased engagement in risk taking behavior is frequently observed in the manic phase of bipolar disorder. In the present study, we analyzed the effect of the most commonly used mood stabilizer lithium on repeated amphetamine treatment-induced risk-taking behaviors in rats using elevated plus maze and wire-beam bridge tests. We found that repeated amphetamine treatment not only increased locomotor activity, but also increased risk taking behaviors in rats, and further that chronic lithium treatment inhibited the amphetamine-increased risk taking behavior. Our studies suggest that these tests may be useful tools to analyze the pharmacological validity of new and improved anti-manic drugs in animals. PMID:26219985

  8. On-fiber derivatization for direct immersion solid-phase microextraction Part I : Acylation of amphetamine with pentafluorobenzoyl chloride

    NARCIS (Netherlands)

    Koster, EHM; Bruins, CHP; Wemes, C; de Jong, GJ

    2001-01-01

    On-fiber derivatization has been used for solid-phase microextraction (SPME) with gas chromatography in order to increase the extractability and detectability. Amphetamine, which has been used as a model compound, was derivatized with pentafluorobenzoyl chloride that was loaded on the fiber prior to

  9. The d-amphetamine-treated Göttingen miniature pig: an animal model for assessing behavioral effects of antipsychotics

    NARCIS (Netherlands)

    Staay, van der F.J.; Pouzet, B.; Mahieu, M.; Nordquist, R.E.; Schuurman, T.

    2009-01-01

    Rationale Rodents are usually used to assess the ability of antipsychotic drugs to antagonize hyperlocomotion induced by dopamine agonists, such as the psychostimulant d-amphetamine. However, the substantial differences between rodents and humans may hinder extrapolation of experimental results to h

  10. Fluctuation of the dopamine uptake inhibition potency of cocaine, but not amphetamine, at mammalian cells expressing the dopamine transporter

    OpenAIRE

    Ukairo, Okechukwu T.; Ramanujapuram, Suneetha; Surratt, Christopher K.

    2006-01-01

    Cocaine, amphetamines and other psychostimulants inhibit synaptic dopamine uptake by interfering with dopamine transporter (DAT) function. The resultant potentiation of dopaminergic neurotransmission is associated with psychostimulant addiction. Fluctuations in dopamine uptake inhibition potency (DUIP) were observed for classical DAT blockers including cocaine, mazindol, methylphenidate (Ritalin™) and benztropine in CHO cells expressing wildtype DAT; cocaine potency also decreased in DAT-expr...

  11. 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 ...

  12. Immunohistochemical localization of cocaine- and amphetamine-regulated transcript peptide in the central nervous system of the frog Rana esculenta

    NARCIS (Netherlands)

    Lazar, G.; Calle, M.; Roubos, E.W.; Kozicz, L.T.

    2004-01-01

    ddThe distribution of cocaine- and amphetamine-regulated transcript peptide (CARTp)-like immunoreactivity was studied only in the rat central nervous system (CNS). In mammals, CART peptides occur among others in brain areas that control feeding behavior. We mapped CARTp-immunoreactive structures in

  13. 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.

  14. Effects of "D"-Amphetamine and Ethanol on Variable and Repetitive Key-Peck Sequences in Pigeons

    Science.gov (United States)

    Ward, Ryan D.; Bailey, Ericka M.; Odum, Amy L.

    2006-01-01

    This experiment assessed the effects of "d"-Amphetamine and ethanol on reinforced variable and repetitive key-peck sequences in pigeons. Pigeons responded on two keys under a multiple schedule of Repeat and Vary components. In the Repeat component, completion of a target sequence of right, right, left, left resulted in food. In the Vary component,…

  15. 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.

  16. The role of dopamine receptor subtypes in the discriminative stimulus effects of amphetamine and cocaine in rats.

    Science.gov (United States)

    Filip, M; Przegaliński, E

    1997-01-01

    The role of dopamine (DA) receptor subtypes in the discriminative stimuli of the psychostimulant drugs of abuse amphetamine and cocaine was evaluated by the ability of DA D1, D2 and D3 receptor subtype ligands to either substitute for or antagonize these effects. Separate groups of rats were trained to discriminate between amphetamine (0.5 mg/kg) and saline, and between cocaine (5 mg/kg) and saline. Both the training drugs evoked cross-substitution. In further substitution experiments, (+)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H -3-benzazepine (SKF 38393; 5-20 mg/kg), a selective D1 agonist, moderately substituted for cocaine, but not for amphetamine. The D2 agonist bromocriptine (2.5-20 mg/kg) mimicked both training drugs' cues. Pramipexole, a D3-preferring agonist, in a dose of 0.5 mg/kg induced over 80% substitution for cocaine, and a weaker one (ca. 62%) for amphetamine. Combination tests with DA antagonists showed that the D1 antagonist (+)-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H -3-benzazepine (SCH 23390; 0.01-2 mg/kg), and the D2 blocker raclopride (0.13-1 mg/kg) significantly (78-100%) attenuated the effects of psychostimulants, while the D3-preferring antagonist cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin (UH 232; 5-20 mg/kg) did not affect them. The present results indicate a critical role of D2 receptor subtypes in the discriminative stimuli of amphetamine and cocaine in rats, as well as a less pronounced involvement of D1 and D3 subtypes in the effects under study. PMID:9431548

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

    International Nuclear Information System (INIS)

    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 H3PO4 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

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

    Science.gov (United States)

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

    2016-09-01

    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. PMID:27367616

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

    Science.gov (United States)

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

    2016-09-01

    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.

  20. Computer aided retrieval of common-batch members in Leuckart amphetamine profiling.

    Science.gov (United States)

    Jonson, C S; Strömberg, L

    1993-11-01

    Comparison of profiles is a well established way to find links between confiscated drugs. It is a laborious and time consuming task to manually compare large numbers of profiles to find common-batch links. To facilitate the comparison a computerized method has been developed. It is described and applied to a set of amphetamine impurity profiles. From each profile, areas of selected peaks are fed to the computer. By using quotients of corresponding peaks, the computer finds pairs of closely related profiles. With a sufficient numbers of peaks, the method is tolerant to variations in intensity between profiles, random peak area variations and a few strongly deviating peak areas. The program was written in Q-basic from Microsoft and may be run on any IBM-compatible personal computer. The method may also be used for analyzing data from other forensic objects, when the descriptors chosen are affected by errors like those described in the text. PMID:8263489

  1. Boltushka: A Homemade Amphetamine-Type Stimulant and HIV Risk in Odessa, Ukraine

    Science.gov (United States)

    Chintalova-Dallas, Repsina; Case, Patricia; Kitsenko, Nataliya; Lazzarini, Zita

    2009-01-01

    Background Homemade amphetamine-type stimulants (ATSs) have been reported in Russia and Eastern Europe for decades. Recipes differ geographically and over time producing differing active ingredients. Vint and jeff (active ingredients methamphetamine and methcathinone, respectively) are two such homemade ATSs originally produced from over-the-counter cold medications and household chemicals. Methods During a Rapid Policy Assessment and Responses (RPAR) project in Odessa, Ukraine, researchers found use of boltushka, a novel homemade ATS. Fourteen supplemental qualitative interviews were conducted, including ten interviews with boltushka injectors and four interviews with pharmacists. We report patterns of boltushka use among local injection drug users (IDUs) as well as the role of laws, regulations, and current pharmacy practices. Results Legal restrictions on over-the-counter cold medicines in Ukraine led to products containing phenypropanolamine (PPA), which oxidized with KMnO4 (potassium permanganate), produces a weak ATS, cathinone, called boltushka. Boltushka’s ingredients are easily available in pharmacies or on the black market. IDUs reported a mean age at first use of 16 years old (range 12–21). While published data are scant, anecdotal evidence reported here include amphetamine-like effects on energy and appetite, binging patterns of use, and some reports of shaking and other neurological damage consistent with earlier reports from exposure to KMnO4. Users reported sharing syringes and other non-sterile injection practices. No users reported specific treatment or prevention programs for boltushka users. Conclusions Although Ukrainian government regulations have limited access to precursor chemicals, IDUs have continued to make and use boltushka. The actual extent and demographics of boltushka use are unknown. Besides risk of bloodborne disease, the health effects of injected homemade ATSs and their constituent chemicals are poorly documented

  2. A Single Amphetamine Infusion Reverses Deficits in Dopamine Nerve-Terminal Function Caused by a History of Cocaine Self-Administration

    OpenAIRE

    Ferris, Mark J.; Calipari, Erin S.; Rose, Jamie H.; Siciliano, Cody A.; Sun, Haiguo; Chen, Rong; JONES, SARA R.

    2015-01-01

    There are ∼1.6 million people who meet the criteria for cocaine addiction in the United States, and there are currently no FDA-approved pharmacotherapies. Amphetamine-based dopamine-releasing drugs have shown efficacy in reducing the motivation to self-administer cocaine and reducing intake in animals and humans. It is hypothesized that amphetamine acts as a replacement therapy for cocaine through elevation of extracellular dopamine levels. Using voltammetry in brain slices, we tested the abi...

  3. The Anorexigenic Peptide Neuromedin U (NMU) Attenuates Amphetamine-Induced Locomotor Stimulation, Accumbal Dopamine Release and Expression of Conditioned Place Preference in Mice.

    Science.gov (United States)

    Vallöf, Daniel; Vestlund, Jesper; Engel, Jörgen A; Jerlhag, Elisabet

    2016-01-01

    Amphetamine dependence, besides its substantial economical consequence, is a serious cause of mortality and morbidity. By investigations of the neurochemical correlates through which addictive drugs, such as amphetamine, activate the mesoaccumbal dopamine system unique targets for treatment of drug addiction can be identified. This reward link consists of a dopamine projection from the ventral tegmental area to the nucleus accumbens (NAc) suggesting that these brain areas are important for reward. The physiological function of gut-brain peptides has expanded beyond food intake modulation and involves regulation of drug reinforcement. A novel candidate for reward regulation is the anorexigenic peptide neuromedin U (NMU). We therefore investigated the effects of intracerebroventricular (icv) administration of NMU on amphetamine's well-documented effects on the mesoaccumbal dopamine system, i.e. locomotor stimulation and accumbal dopamine release in mice. In addition, the effect of accumbal NMU administration on locomotor activity was examined. The effect of NMU, icv or intra-NAc, on the expression of conditioned place preference (CPP) was elucidated. Firstly, we showed that icv administration of NMU attenuate the amphetamine-induced locomotor stimulation, accumbal dopamine release and expression of CPP in mice. Secondly, we found that a lower dose of NMU (icv) reduce the amphetamine-induced locomotor stimulation in mice. Thirdly, we demonstrated that NMU administration into the NAc block the ability of amphetamine to cause a locomotor stimulation in mice. However, accumbal NMU administration did not attenuate the amphetamine-induced expression of CPP in mice. Our novel data suggest that central NMU signalling is involved in development of amphetamine dependence. PMID:27139195

  4. The Anorexigenic Peptide Neuromedin U (NMU Attenuates Amphetamine-Induced Locomotor Stimulation, Accumbal Dopamine Release and Expression of Conditioned Place Preference in Mice.

    Directory of Open Access Journals (Sweden)

    Daniel Vallöf

    Full Text Available Amphetamine dependence, besides its substantial economical consequence, is a serious cause of mortality and morbidity. By investigations of the neurochemical correlates through which addictive drugs, such as amphetamine, activate the mesoaccumbal dopamine system unique targets for treatment of drug addiction can be identified. This reward link consists of a dopamine projection from the ventral tegmental area to the nucleus accumbens (NAc suggesting that these brain areas are important for reward. The physiological function of gut-brain peptides has expanded beyond food intake modulation and involves regulation of drug reinforcement. A novel candidate for reward regulation is the anorexigenic peptide neuromedin U (NMU. We therefore investigated the effects of intracerebroventricular (icv administration of NMU on amphetamine's well-documented effects on the mesoaccumbal dopamine system, i.e. locomotor stimulation and accumbal dopamine release in mice. In addition, the effect of accumbal NMU administration on locomotor activity was examined. The effect of NMU, icv or intra-NAc, on the expression of conditioned place preference (CPP was elucidated. Firstly, we showed that icv administration of NMU attenuate the amphetamine-induced locomotor stimulation, accumbal dopamine release and expression of CPP in mice. Secondly, we found that a lower dose of NMU (icv reduce the amphetamine-induced locomotor stimulation in mice. Thirdly, we demonstrated that NMU administration into the NAc block the ability of amphetamine to cause a locomotor stimulation in mice. However, accumbal NMU administration did not attenuate the amphetamine-induced expression of CPP in mice. Our novel data suggest that central NMU signalling is involved in development of amphetamine dependence.

  5. The Anorexigenic Peptide Neuromedin U (NMU) Attenuates Amphetamine-Induced Locomotor Stimulation, Accumbal Dopamine Release and Expression of Conditioned Place Preference in Mice

    OpenAIRE

    Daniel Vallöf; Jesper Vestlund; Engel, Jörgen A; Elisabet Jerlhag

    2016-01-01

    Amphetamine dependence, besides its substantial economical consequence, is a serious cause of mortality and morbidity. By investigations of the neurochemical correlates through which addictive drugs, such as amphetamine, activate the mesoaccumbal dopamine system unique targets for treatment of drug addiction can be identified. This reward link consists of a dopamine projection from the ventral tegmental area to the nucleus accumbens (NAc) suggesting that these brain areas are important for re...

  6. Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions

    OpenAIRE

    Rubin Gulaboski; Natalia N D S Cordeiro; Nuno Milhazes; Jorge Garrido; Fernanda Borges; Miguel Jorge; Pereira, Carlos M.; Ivan Bogeski; Aluska Helguera Morales; Blaze Naumoski; Fernando F Silva

    2007-01-01

    For the first time, the partition coefficients of the ionized forms of several opioids, amphetamine-like drugs, and their metabolites were determined by studying their ionic transfer process across the bare interface waterjorganic solvent. The ionic partition coefficients of the monocationic forms of 12 compounds—heroin, 6-monoacetylmorphine (6-MAM), morphine, acetylcodeine, codeine, dihydrocodeine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA or ‘‘ecstasy’’)...

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

    International Nuclear Information System (INIS)

    The effect of reserpine on the inhibition by (+)-amphetamine and cocaine of the accumulation of 3H-dopamine (DA) in striatal slices and 3H-noradrenaline (NA) in slices of cerebral occipital cortex and heart atrium of rats and the release of the 3H-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 3H-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)

  8. A comparison of the effects of methylphenidate and amphetamine on the simultaneous release of radiolabelled dopamine and p- or m-tyramine from rat striatal slices

    International Nuclear Information System (INIS)

    The release of [14C]dopamine (DA) from slices of rat caudate nucleus was studied simultaneously with the release of either [3H]para-tyramine (pTA) or [3H]meta-tyramine (mTA). Amphetamine (10-5M) caused a large concurrent release of [14C]DA and [3H]pTA; similar results were obtained when [14C]DA and [3H]mTA release were studied. The release of all three amines by amphetamine was quantitatively similar. In contrast, methylphenidate caused a release of [3H]pTA similar to that seen with amphetamine, but only a very small simultaneous release of [14C]DA. [3H]mTA was also strongly released by methylphenidate concurrent with a minimal release of [14C]DA. The inclusion of reserpine in the incubation medium had no detectable effect on the release of any of the three amines by amphetamine. Methylphenidate-induced release of tritiated mTA and pTA was also unaffected by reserpine. However, the release of [14C]DA by methylphenidate was potentiated in the presence of reserpine. The uptake of radiolabelled pTA, mTA and DA was inhibited by both amphetamine and methylphenidate, although amphetamine was a stronger inhibitor of the uptake of all three amines. It is suggested that release of endogenous tyramines may be involved in mediating some actions of psychomotor stimulant drugs. (Auth.)

  9. The reinforcing, subject-rated, performance, and cardiovascular effects of d-amphetamine: Influence of sensation-seeking status

    OpenAIRE

    Stoops, William W.; Lile, Joshua A.; Robbins, C. Glenn; Martin, Catherine A.; Rush, Craig R.; Kelly, Thomas H.

    2006-01-01

    Individual differences that may contribute to vulnerability to abuse drugs have been identified. Sensation-seeking status has been shown to influence both vulnerability to drug use and response to acute drug administration. The purpose of the present experiment was to examine the reinforcing effects of d-amphetamine in high and low sensation-seeking subjects using a modified progressive-ratio procedure. A battery of subject-rated, performance, and cardiovascular measures was also included to ...

  10. Behavioral sensitization and cross-sensitization between methylphenidate amphetamine, and 3-4, methylenedioxymethamphetamine (MDMA) in female SD rats

    OpenAIRE

    Yang, Pamela B; Atkins, Kristal D; Dafny, Nachum

    2011-01-01

    The psychostimulants amphetamine and methylphenidate (MPD / Ritalin) are the drugs most often used to treat attention deficit hyperactivity disorder (ADHD). In addition, students of all ages take these drugs to improve academic performance but also abuse them for pleasurable enhancement. In addition, other psychostimulants such 3,4 methylenedioxymethamphetamine (MDMA / ecstasy) are used / abused for similar objectives. One of the experimental markers for the potential of a drug to produce dep...

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

    OpenAIRE

    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. Th...

  12. Effects of amphetamine exposure in adolescence or young adulthood on inhibitory control in adult male and female rats

    OpenAIRE

    Hammerslag, Lindsey R.; Waldman, Alex J.; Gulley, Joshua M.

    2014-01-01

    Heightened impulsivity is a feature of some psychiatric disorders, including addiction, that also have sex-specific patterns of expression. The relationship between addiction and impulsivity may be driven by drug-induced changes in behavior caused by long term adaptations in signaling within the medial prefrontal cortex (mPFC). Here, we used a response inhibition task that is sensitive to changes in mPFC function to examine the effects of sex and exposure to amphetamine (AMPH) on impulsive ac...

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

    OpenAIRE

    Schmidt, Lene S.; Miller, Anthony D.; Lester, Deranda B.; Bay-Richter, Cecilie; Schülein, Christina; Schmidt, Henriette F.; Wess, Jürgen; Blaha, Charles D.; Woldbye, David P.D.; Fink-Jensen, Anders; Wortwein, Gitta

    2009-01-01

    Muscarinic M5 receptors are the only muscarinic receptor subtype expressed by dopamine-containing neurons of the ventral tegmental area. These cells play an important role for the reinforcing properties of psychostimulants and M5 receptors modulate their activity. Previous studies showed that M5 receptor knockout (M5−/−) mice are less sensitive to the reinforcing properties of addictive drugs. Here we investigate the role of M5 receptors in the effects of amphetamine and cocaine on locomotor ...

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

    OpenAIRE

    Takeshi Kumazawa; Kenji Hara; Chika Hasegawa; Seisaku Uchigasaki; Xiao-Pen Lee; Hiroshi Seno; Osamu Suzuki; Keizo Sato

    2011-01-01

    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 sp...

  15. A Web-Based Intervention for Users of Amphetamine-Type Stimulants: 3-Month Outcomes of a Randomized Controlled Trial

    OpenAIRE

    Tait, Robert J; McKetin, Rebecca; Kay-Lambkin, Frances; Carron-Arthur, Bradley; Bennett, Anthony; Bennett, Kylie; Christensen, Helen; Griffiths, Kathleen M

    2014-01-01

    Background Among illicit drugs, the prevalence of amphetamine-type stimulant (ATS) use is second only to cannabis. Currently, there are no approved pharmacotherapies for ATS problems, but some face-to-face psychotherapies are effective. Web-based interventions have proven to be effective for some substance use problems, but none has specifically targeted ATS users. Objective The objective of the study was to evaluate the effectiveness of a Web-based intervention for ATS problems on a free-to-...

  16. Transcriptome Profiling of Khat (Catha edulis) and Ephedra sinica Reveals Gene Candidates Potentially Involved in Amphetamine-Type Alkaloid Biosynthesis

    OpenAIRE

    Groves, Ryan A.; Hagel, Jillian M.; Zhang, Ye; Kilpatrick, Korey; Levy, Asaf; Marsolais, Frédéric; Lewinsohn, Efraim; Sensen, Christoph W.; Facchini, Peter J.

    2015-01-01

    Amphetamine analogues are produced by plants in the genus Ephedra and by khat (Catha edulis), and include the widely used decongestants and appetite suppressants (1S,2S)-pseudoephedrine and (1R,2S)-ephedrine. The production of these metabolites, which derive from L-phenylalanine, involves a multi-step pathway partially mapped out at the biochemical level using knowledge of benzoic acid metabolism established in other plants, and direct evidence using khat and Ephedra species as model systems....

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

    International Nuclear Information System (INIS)

    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 [3H]-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 [3H]-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 [3H]-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

  18. 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.

  19. ANTIPSYCHOTIC ACTIVITY OF AQUEOUS ETHANOLIC EXTRACT OF TINOSPORA CORDIFOLIA IN AMPHETAMINE CHALLENGED MICE MODEL

    Directory of Open Access Journals (Sweden)

    Abhilasha Shete

    2010-03-01

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

  20. Cocaine- and amphetamine-regulated transcript (CART) protects beta cells against glucotoxicity and increases cell proliferation.

    Science.gov (United States)

    Sathanoori, Ramasri; Olde, Björn; Erlinge, David; Göransson, Olga; Wierup, Nils

    2013-02-01

    Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide that promotes glucose-stimulated insulin secretion in beta cells via cAMP/PKA-dependent pathways. In addition, CART is a regulator of neuronal survival. In this study, we examined the effect of exogenous CART 55-102 on beta cell viability and dissected its signaling mechanisms. Evaluation of DNA fragmentation and chromatin condensation revealed that CART 55-102 reduced glucotoxicity-induced apoptosis in both INS-1 (832/13) cells and isolated rat islets. Glucotoxicity in INS-1 (832/13) cells also caused a 50% reduction of endogenous CART protein. We show that CART increased proliferation in INS-1 (832/13) cells, an effect that was blocked by PKA, PKB, and MEK1 inhibitors. In addition, CART induced phosphorylation of CREB, IRS, PKB, FoxO1, p44/42 MAPK, and p90RSK in INS-1 (832/13) cells and isolated rat islets, all key mediators of cell survival and proliferation. Thus, we demonstrate that CART 55-102 protects beta cells against glucotoxicity and promotes proliferation. Taken together our data point to the potential use of CART in therapeutic interventions targeted at enhancing functional beta cell mass and long-term insulin secretion in T2D. PMID:23250745

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

    International Nuclear Information System (INIS)

    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 (Pcutoff) 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)

  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. Abnormal Behaviors and Microstructural Changes in White Matter of Juvenile Mice Repeatedly Exposed to Amphetamine

    Directory of Open Access Journals (Sweden)

    Hong-Ju Yang

    2011-01-01

    Full Text Available Amphetamine (AMP is an addictive CNS stimulant and has been commonly abused by adolescents and young adults, during which period brain white matter is still developing. This study was to examine the effect of a nonneurotoxic AMP on the white matter of juvenile mice. d-AMP (1.0 mg/kg was given to young male C57BL/6 mice once a day for 21 days. The spatial working memory and locomotion of mice were measured at the end. Then, mice were sacrificed and their brains were processed for morphological analyses to examine the white matter structure and for Western blot analysis to measure three main proteins expressed in mature oligodendrocytes. AMP-treated mice displayed higher locomotion and spatial working memory impairment and showed lower levels of Nogo-A and GST-pi proteins in frontal cortex and lower MBP protein in the frontal cortex and hippocampus. They also had fewer mature oligodendrocytes and weak MBP immunofluorescent staining in the same two brain regions. But the striatum was spared. These results suggest that the late-developing white matter is vulnerable to AMP treatment which is able to increase striatal and cortical dopamine. Both the compromised white matter and increased dopamine may contribute to the observed behavioral changes in AMP-treated mice.

  4. 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....../Discs-large/ZO-1 (PDZ)-binding sequence of DAT, was made membrane-permeable by fusing it to the cell membrane transduction domain of the HIV-1 Tat protein (TAT-C24WT). The ability of TAT-C24WT but not a scrambled peptide (TAT-C24Scr) to block the CaMKIIα-DAT interaction was supported by co......-binding sequence, but preserved CaMKIIα binding (TAT-C24AAA), to diminish AMPH-evoked DA efflux in vivo to the same extent as TAT-C24WT. Finally, AMPH-induced locomotor hyperactivity was attenuated following systemic administration of TAT-C24WT but not TAT-C24Scr. Summarized, our findings substantiate that DAT C...

  5. 123I-amphetamine-SPECT in the diagnosis of neurological disorders

    International Nuclear Information System (INIS)

    In contrast to conventional brain scintigraphy with sup(99m)Tc-pertechnetate, SPECT with 123I-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 123I-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.)

  6. 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. PMID:26433325

  7. Analysis of the mechanisms by which amphetamine releases dopamine from striatal dopaminergic neurons

    International Nuclear Information System (INIS)

    The goals of the studies were (1) to determine the intraneuronal transmitter pools that contribute to the efflux of dopamine (DA) elicited by amphetamine (AMPH) and (2) to determine the biochemical mechanism by which AMPH increases DA efflux from dopaminergic neurons. AMPH increased the efflux of endogenous DA and decreased the electrically-evoked overflow of [3H] acetylcholine (ACh) from superfused rabbit striatal slices. These effects were most pronounced when both vesicular DA stores and DA synthesis were intact. Therefore, extravesicular, newly synthesized DA and vesicular stores of DA contribute to AMPH-induced DA efflux. Simultaneous inhibition of monoamine oxidase (MAO) and neuronal DA uptake did not increase the efflux of endogenous DA or inhibit the electrically-evoked overflow of [3H]ACh to the same extent as AMPH. Hence, inhibition of MAO and neuronal DA uptake are probably not the major mechanisms by which AMPH increases DA efflux. The AMPH-induced efflux of endogenous or [3H]DA was blocked by inhibitors of neuronal DA uptake

  8. Advances and challenges in pharmacotherapeutics for amphetamine-type stimulants addiction.

    Science.gov (United States)

    Cao, Dan-Ni; Shi, Jing-Jing; Hao, Wei; Wu, Ning; Li, Jin

    2016-06-01

    Addiction to amphetamine-type stimulants (ATS) is a serious worldwide public health problem with major medical, psychiatric and socioeconomic consequences. However, no approved pharmacological therapies are available to treat ATS addiction. Based on the neurobiological mechanisms underlying ATS addiction, the recent research works about pharmacological strategies have been focused on monoamine, glutamate, endogenous opioid peptide and γ-amino butyric acid (GABA) systems. This review summarizes the recent advances in the medications being developed to treat ATS addiction and discusses the remaining challenges. Although no substantial evidence for efficacious medications has emerged, some of these agents, including bupropion, naltrexone and mirtazapine, have demonstrated promise in clinical studies. Moreover, some challenges, such as the development of new preclinical animal models of drug addiction, the design of large-scale clinical trials with strict quality control, and the distinction of patients' genetic polymorphisms, need further attention. Despite the lack of success to date, much effort is being made to develop efficacious medications for treating ATS addiction. PMID:27018393

  9. Development of a harmonised method for the profiling of amphetamines V: Determination of the variability of the optimised method.

    Science.gov (United States)

    Lock, Eric; Aalberg, Laura; Andersson, Kjell; Dahlén, Johan; Cole, Michael D; Finnon, Yvonne; Huizer, Henk; Jalava, Kaisa; Kaa, Elisabet; Lopes, Alvaro; Poortman-van der Meer, Anneke; Sippola, Erkki

    2007-06-14

    This paper is the fifth in a series of six in relation to the development of a harmonised method for the profiling of amphetamine [L. Aalberg, K. Andersson, C. Bertler, H. Borén, M.D. Cole, J. Dahlén, Y. Finnon, H. Huizer, K. Jalava, E. Kaa, E. Lock, A. Lopes, A. Poortman-van der Meer, E. Sippola, Development of a harmonised method for the profiling of amphetamines I. Synthesis of standards and compilation of analytical data, Forensic Sci. Int. 149 (2005) 219-229; L. Aalberg, K. Andersson, C. Bertler, M.D. Cole, Y. Finnon, H. Huizer, K. Jalava, E. Kaa, E. Lock, A. Lopes, A. Poortman-van der Meer, E. Sippola, J. Dahlén, Development of a harmonised method for the profiling of amphetamines II. Stability of impurities in organic solvents, Forensic Sci. Int. 149 (2005) 231-241]. The third paper [K. Andersson, K. Jalava, E. Lock, L. Aalberg, Y. Finnon, H. Huizer, E. Kaa, A. Lopes, A. Poortman-van der Meer, M.D. Cole, J. Dahlén, E. Sippola, Development of a harmonised method for the profiling of amphetamines III. Development of the gas chromatographic method, Forensic Sci. Int., in press] dealt with the optimisation of the gas chromatographic and detection methods whereas the fourth paper [K. Andersson, K. Jalava, E. Lock, Y. Finnon, S. Stevenson, L. Aalberg, H. Huizer, E. Kaa, A. Lopes, A. Poortman-van der Meer, M.D. Cole, J. Dahlén, E. Sippola, Development of a harmonised method for the profiling of amphetamines IV. Optimisation of sample preparation, Forensic Sci. Int., in press] concerned the optimisation of the extraction method prior to GC analysis. This paper is a study of the optimised method in order to determine its stability. Investigations of within and between day variations were carried out in four laboratories. Moreover, variations between laboratories were also determined. Both flame ionisation detector (FID) and MS detection were used. One laboratory studied nitrogen-phosphorous detector (NPD) detection as well. For this task, 12 batches of

  10. The Anorexigenic Peptide Neuromedin U (NMU) Attenuates Amphetamine-Induced Locomotor Stimulation, Accumbal Dopamine Release and Expression of Conditioned Place Preference in Mice

    Science.gov (United States)

    Vallöf, Daniel; Vestlund, Jesper; Engel, Jörgen A.; Jerlhag, Elisabet

    2016-01-01

    Amphetamine dependence, besides its substantial economical consequence, is a serious cause of mortality and morbidity. By investigations of the neurochemical correlates through which addictive drugs, such as amphetamine, activate the mesoaccumbal dopamine system unique targets for treatment of drug addiction can be identified. This reward link consists of a dopamine projection from the ventral tegmental area to the nucleus accumbens (NAc) suggesting that these brain areas are important for reward. The physiological function of gut-brain peptides has expanded beyond food intake modulation and involves regulation of drug reinforcement. A novel candidate for reward regulation is the anorexigenic peptide neuromedin U (NMU). We therefore investigated the effects of intracerebroventricular (icv) administration of NMU on amphetamine’s well-documented effects on the mesoaccumbal dopamine system, i.e. locomotor stimulation and accumbal dopamine release in mice. In addition, the effect of accumbal NMU administration on locomotor activity was examined. The effect of NMU, icv or intra-NAc, on the expression of conditioned place preference (CPP) was elucidated. Firstly, we showed that icv administration of NMU attenuate the amphetamine-induced locomotor stimulation, accumbal dopamine release and expression of CPP in mice. Secondly, we found that a lower dose of NMU (icv) reduce the amphetamine-induced locomotor stimulation in mice. Thirdly, we demonstrated that NMU administration into the NAc block the ability of amphetamine to cause a locomotor stimulation in mice. However, accumbal NMU administration did not attenuate the amphetamine-induced expression of CPP in mice. Our novel data suggest that central NMU signalling is involved in development of amphetamine dependence. PMID:27139195

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

    Science.gov (United States)

    Burghardt, P R; Krolewski, D M; Dykhuis, K E; Ching, J; Pinawin, A M; Britton, S L; Koch, L G; Watson, S J; Akil, H

    2016-05-01

    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. Differential influence of dopamine transport rate on the potencies of cocaine, amphetamine, and methylphenidate.

    Science.gov (United States)

    Calipari, Erin S; Ferris, Mark J; Siciliano, Cody A; Jones, Sara R

    2015-01-21

    Dopamine transporter (DAT) levels vary across brain regions and individuals, and are altered by drug history and disease states; however, the impact of altered DAT expression on psychostimulant effects in brain has not been systematically explored. Using fast scan cyclic voltammetry, we measured the effects of elevated DAT levels on presynaptic dopamine parameters as well as the uptake inhibition potency of the blockers cocaine and methylphenidate (MPH) and the releaser amphetamine (AMPH) in the nucleus accumbens core. Here we found that increases in DAT levels, resulting from either genetic overexpression or MPH self-administration, caused markedly increased maximal rates of uptake (Vmax) that were positively correlated with the uptake inhibition potency of AMPH and MPH, but not cocaine. AMPH and MPH were particularly sensitive to DAT changes, with a 100% increase in Vmax resulting in a 200% increase in potency. The relationship between Vmax and MPH potency was the same as that for AMPH, but was different from that for cocaine, indicating that MPH more closely resembles a releaser with regard to uptake inhibition. Conversely, the effects of MPH on stimulated dopamine release were similar to those of cocaine, with inverted U-shaped increases in release over a concentration-response curve. This was strikingly different from the release profile of AMPH, which showed only reductions at high concentrations, indicating that MPH is not a pure releaser. These data indicate that although MPH is a DAT blocker, its uptake-inhibitory actions are affected by DAT changes in a similar manner to releasers. Together, these data show that fluctuations in DAT levels alter the potency of releasers and MPH but not blockers and suggest an integral role of the DAT in the addictive potential of AMPH and related compounds. PMID:25474655

  13. Nicotine regulates cocaine-amphetamine-Regulated Transcript (Cart) in the mesocorticolimbic system.

    Science.gov (United States)

    Kaya, Egemen; Gozen, Oguz; Ugur, Muzeyyen; Koylu, Ersin O; Kanit, Lutfiye; Balkan, Burcu

    2016-07-01

    Cocaine-and-Amphetamine Regulated Transcript (CART) mRNA and peptides are intensely expressed in the brain regions comprising mesocorticolimbic system. Studies suggest that CART peptides may have a role in the regulation of reward circuitry. The present study aimed to examine the effect of nicotine on CART expression in the mesocorticolimbic system. Three different doses of nicotine (0.2, 0.4, 0.6 mg/kg free base) were injected subcutaneously for 5 days, and on day 6, rats were decapitated following a challenge dose. CART mRNA and peptide levels in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum (DST), amygdala (AMG), lateral hypothalamic area (LHA), and ventral tegmental area (VTA) were measured by quantitative real-time PCR (qPCR) and Western Blot analysis, respectively. In the mPFC, 0.4 and 0.6 mg/kg nicotine, decreased CART peptide levels whereas there was no effect on CART mRNA levels. In the VTA, a down-regulation of CART peptide expression was observed with 0.2 and 0.6 mg/kg nicotine. Conversely, 0.4 and 0.6 mg/kg nicotine increased CART mRNA levels in the AMG without affecting the CART peptide expression. Nicotine did not regulate CART mRNA or CART peptide expression in the NAc, DST, and LHA. We conclude that nicotine regulates CART expression in the mesocorticolimbic system and this regulation may play an important role in nicotine reward. Synapse 70:283-292, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990424

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

    International Nuclear Information System (INIS)

    The accumulation of 5 nM d-[3H]amphetamine (d-[3H]AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-[3H]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-[3H]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 [3H] 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-[3H]AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed

  15. Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. II. Active transport

    Energy Technology Data Exchange (ETDEWEB)

    Zaczek, R.; Culp, S.; De Souza, E.B. (Addiction Research Center, Baltimore, MD (USA))

    1991-05-01

    The accumulation of 5 nM d-({sup 3}H)amphetamine (d-({sup 3}H)AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-({sup 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-({sup 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 ({sup 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-({sup 3}H)AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed.

  16. 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. PMID:23116635

  17. 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.

  18. Chronic caffeine produces sexually dimorphic effects on amphetamine-induced behavior, anxiety and depressive-like behavior in adolescent rats.

    Science.gov (United States)

    Turgeon, Sarah M; Townsend, Shannon E; Dixon, Rushell S; Hickman, Emma T; Lee, Sabrina M

    2016-04-01

    Caffeine consumption has been increasing rapidly in adolescents; however, most research on the behavioral effects of caffeine has been conducted in adults. Two experiments were conducted in which adolescent male and female rats were treated with a moderate dose of caffeine (0.25g/l) in their drinking water beginning on P26-28. In the first experiment, animals were maintained on caffeinated drinking water or normal tap water for 14days and were then tested for behavioral and striatal c-Fos response to amphetamine (1.5mg/kg). In the second experiment, rats were maintained on caffeinated drinking water or normal tap water beginning on P28 and were tested for novel object recognition, anxiety in the light/dark test (L/D) and elevated plus maze (EPM), and depressive like behavior in the forced swim test (FST) beginning on the 14th day of caffeine exposure. Caffeine decreased amphetamine-induced rearing in males, but had no effect in females; however, this behavioral effect was not accompanied by changes in striatal c-Fos, which was increased by amphetamine but not altered by caffeine. No effects of caffeine were observed on novel object recognition or elevated plus maze behavior. However, in the L/D test, there was a sex by caffeine interaction on time spent in the light driven by a caffeine-induced increase in light time in the males but not the females. On the pretest day of the FST, sex by caffeine interactions were observed for swimming and struggling; caffeine decreased struggling behavior and increased swimming behavior in males and caffeine-treated females demonstrated significantly more struggling and significantly less swimming than caffeine-treated males. A similar pattern was observed on the test day in which caffeine decreased immobility overall and increased swimming. These data reveal sex dependent effects of caffeine on behavior in adolescent rats. PMID:26850920

  19. 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.

  20. Transcriptome profiling of khat (Catha edulis) and Ephedra sinica reveals gene candidates potentially involved in amphetamine-type alkaloid biosynthesis.

    Science.gov (United States)

    Groves, Ryan A; Hagel, Jillian M; Zhang, Ye; Kilpatrick, Korey; Levy, Asaf; Marsolais, Frédéric; Lewinsohn, Efraim; Sensen, Christoph W; Facchini, Peter J

    2015-01-01

    Amphetamine analogues are produced by plants in the genus Ephedra and by khat (Catha edulis), and include the widely used decongestants and appetite suppressants (1S,2S)-pseudoephedrine and (1R,2S)-ephedrine. The production of these metabolites, which derive from L-phenylalanine, involves a multi-step pathway partially mapped out at the biochemical level using knowledge of benzoic acid metabolism established in other plants, and direct evidence using khat and Ephedra species as model systems. Despite the commercial importance of amphetamine-type alkaloids, only a single step in their biosynthesis has been elucidated at the molecular level. We have employed Illumina next-generation sequencing technology, paired with Trinity and Velvet-Oases assembly platforms, to establish data-mining frameworks for Ephedra sinica and khat plants. Sequence libraries representing a combined 200,000 unigenes were subjected to an annotation pipeline involving direct searches against public databases. Annotations included the assignment of Gene Ontology (GO) terms used to allocate unigenes to functional categories. As part of our functional genomics program aimed at novel gene discovery, the databases were mined for enzyme candidates putatively involved in alkaloid biosynthesis. Queries used for mining included enzymes with established roles in benzoic acid metabolism, as well as enzymes catalyzing reactions similar to those predicted for amphetamine alkaloid metabolism. Gene candidates were evaluated based on phylogenetic relationships, FPKM-based expression data, and mechanistic considerations. Establishment of expansive sequence resources is a critical step toward pathway characterization, a goal with both academic and industrial implications. PMID:25806807

  1. 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. PMID:24183825

  2. 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...... cases and to 5.9 ng/mg of MDMA in 13 cases. MA was only detected once at trace level. The method, including the derivatization procedure, is simple and robust with a sensitivity that is satisfactory for measurement of amphetamines and ecstasy in hair from abusers....

  3. Activation of group III metabotropic glutamate receptors inhibits basal and amphetamine-stimulated dopamine release in rat dorsal striatum: an in vivo microdialysis study.

    Science.gov (United States)

    Mao, L; Lau, Y S; Wang, J Q

    2000-09-22

    Group III metabotropic glutamate (mGlu) receptors are negatively coupled to adenylate cyclase and are distributed pre-synaptically in the striatum. A behavioral study previously conducted in this laboratory shows that activation of this group of mGlu receptors attenuates acute amphetamine-stimulated motor activity. By administering a group III selective agonist or antagonist via the dialysis probe, the present study employed in vivo microdialysis to evaluate the capacity of the group III selective agents to alter extracellular levels of dopamine in the dorsal striatum of normal and amphetamine-treated rats. It was found that the group III agonist L-2-amino-4-phosphonobutyrate (L-AP4) dose-dependently (1, 10 and 100 microM) reduced basal levels of extracellular dopamine. In contrast, the group III antagonist alpha-methyl-4-phosphonophenylglycine (MPPG) dose-dependently (10, 50 and 250 microM) elevated the basal release of extracellular dopamine. This elevation was antagonized by co-perfusion of L-AP4. Perfusion of 5-microM amphetamine through the dialysis probe increased extracellular dopamine in the dorsal striatum. Co-perfusion of L-AP4 (100 microM) significantly reduced amphetamine-stimulated dopamine levels, whereas co-perfusion of L-AP4 (100 microM) and MPPG (100 microM) did not alter the capacity of amphetamine to elicit dopamine release. The data obtained from this study demonstrate the presence of a tonically active glutamatergic tone on group III mGlu receptors in the dorsal striatum to pre-synaptically regulate basal dopamine release in an inhibitory fashion. Moreover, activation of L-AP4-sensitive group III mGlu receptors can suppress the phasic release of dopamine induced by a dopamine stimulant amphetamine. PMID:10996594

  4. The effects of (+)-amphetamine, alpha-methyltyrosine, and alpha-methylphenylalanine on the concentrations of m-tyramine and alpha-methyl-m-tyramine in rat striatum.

    OpenAIRE

    Dougan, D. F.; Duffield, A. M.; Duffield, P. H.; Wade, D. N.

    1983-01-01

    The concentration in rat striatum of the meta and para isomers of tyramine and alpha-methyltyramine, after the administration of (+)-amphetamine, alpha-methyl-p-tyrosine (AMPT) and alpha-methylphenylalanine (AMPA) has been determined using chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.). Twenty hours after the last of 7 daily injections of (+)-amphetamine (5 mg kg-1 i.p.) the concentration of alpha-methyl-p-tyramine in striatal tissue increased twofold compared to the ...

  5. 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.

  6. 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.

    2016-02-01

    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.

  7. Simultaneous enantioselective determination of amphetamine and congeners in hair specimens by negative chemical ionization gas chromatography-mass spectrometry.

    Science.gov (United States)

    Martins, Liliane; Yegles, Michel; Chung, Heesun; Wennig, Robert

    2005-10-15

    Enantioselective quantification of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA) enantiomers in hair using gas chromatography-mass spectrometry (GC-MS) is described. Hair specimens were digested with 1M sodium hydroxide at 100 degrees C for 30 min and extracted by a solid phase procedure using Cleanscreen ZSDAU020. Extracted analytes were derivatised with (S)-heptafluorobutyrylprolyl chloride and the resulting diastereoisomers were quantified by GC-MS operating in the negative chemical ionization mode. Extraction yields were between 73.0 and 97.9%. Limits of detection varied in the range of 2.1-45.9 pg/mg hair, whereas the lowest limits of quantification varied between 4.3 and 91.8 pg/mg hair. Intra- and inter-assay precision and respective accuracy were acceptable. The enantiomeric ratios (R versus S) of AM, MA, MDA, MDMA and MDEA were determined in hair from suspected amphetamine abusers. Only MA and AM enantiomers were detectable in this collective and the quantification data showed in most cases higher concentrations of (R)-MA and (R)-AM than those of the corresponding (S)-enantiomers. PMID:16154523

  8. 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.

  9. Differences in the cellular mechanism underlying the effects of amphetamine on prepulse inhibition in apomorphine-susceptible and apomorphine-unsusceptible rats.

    NARCIS (Netherlands)

    Elst, M.C.J. van der; Wunderink, Y.S.; Ellenbroek, B.A.; Cools, A.R.

    2007-01-01

    BACKGROUND: Amphetamine is often used to mimic certain aspects of schizophrenia in laboratory animals, such as a decreased prepulse inhibition. MATERIALS AND METHODS: Apomorphine-susceptible and apomorphine-unsusceptible rats represent a well-characterized animal model for individual differences in

  10. 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; Holst, Jens Juul; Warberg, J; Vrang, N

    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 hypothalamic...

  11. Analysis of the impulsive aggression and decision-making ability in the inpatients with amphetamine-type stimulants-induced psychiatric disorders

    Institute of Scientific and Technical Information of China (English)

    苏中华

    2014-01-01

    Objective To understand the characteristics of impulsive aggression and the ability of decision-making in the inpatients with amphetamine-type stimulants(ATS)-induced psychiatric disorder,and explore their changes before and after treatment with antipsychotic drugs.Methods One hundred inpatients(patient group)who met the diagnostic criterion of ATS-induced psychiatric

  12. 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...... hospitalized medical patients....

  13. 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.

  14. 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.

  15. 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

    2016-05-01

    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 1 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

  16. 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

    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......-amph), 4) THERAPY (embolized, saline + physical therapy) and 5) D-AMPH + THERAPY (embolized, D-amph + physical therapy). Rats of the groups 4-5 underwent d-amph or saline treatment on days 1, 3, 5 and 7 after surgery and were re-trained for 1 h starting 60 min after each treatment. During this time, rats...... 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...

  17. Impurities in Illicit Drug Preparations: 3,4-(Methylenedioxy)amphetamine and 3,4-(Methylenedioxy)methylamphetamine.

    Science.gov (United States)

    Verweij, A M

    1992-12-01

    Attention is given here to the mass spectral data of impurities present in illicit drug preparations of 3,4-(methylenedioxy)amphetamine and 3,4-(methylenedioxy)methylamphetamine. These "designer" drugs, having emphatic properties, were synthesized following well-known procedures such as the reductive amination route, the Leuckart reaction, and the nitropropene and the bromopropane routes. Based on the structure elucidation of impurities - especially those so-called "route specific" ones - present in these illicit drug preparations conclusions can be drawn about the method of preparation of a drug sample. Furthermore, on the basis of this kind of information methods can be developed for the comparison of drug samples, by which questions about the origin of drug samples can be solved (commonly known as the signature method). PMID:26267375

  18. A scoping review of home-produced heroin and amphetamine-type stimulant substitutes: implications for prevention, treatment, and policy.

    Science.gov (United States)

    Hearne, Evelyn; Grund, Jean-Paul Cornelius; Van Hout, Marie Claire; McVeigh, Jim

    2016-01-01

    Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and internal organ damage. The high incidence of HIV rates amongst people who inject home-produced substances is a public health concern. The resulting physical health consequences of injecting these crude substances are very severe in comparison to heroin or amphetamine acquired in black markets. Due to this fact and the increased mortality associated with these substances, professionals in the area of prevention, treatment, and policy development need to be cognisant of the presentation, harms, and the dangers associated with home-produced substances globally. This scoping review aimed to examine existing literature on the subject of home-produced heroin and amphetamine-type stimulant substitutes. The review discussed the many implications such research may have in the areas of policy and practice. Data were gathered through the use of qualitative secondary resources such as journal articles, reports, reviews, case studies, and media reports. The home production of these substances relies on the utilisation of precursor drugs such as less potent stimulants, tranquillizers, analgesics, and sedatives or natural plant ingredients. The Internet underpins the facilitation of this practice as recipes, and diverted pharmaceutical sales are available widely online, and currently, ease of access to the Internet is evident worldwide. This review highlights the necessity of prevention, education, and also harm reduction related to home-produced drugs and also recommends consistent monitoring

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

    International Nuclear Information System (INIS)

    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 R2 = 0.73 and Q2 = 0.60, with external predictability Q2 = 0.68, and R2 = 0.76 and Q2 = 0.67 with external predictability Q2 = 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.

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

    International Nuclear Information System (INIS)

    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 QuantisalTM 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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. PMID:27091701

  3. The synthesis, mass spectrometric properties and identification of some N,N-di-(β-arylisopropyl)formamides related to the synthesis of ring-modified amphetamines.

    Science.gov (United States)

    Błachut, Dariusz; Danikiewicz, Witold; Wojtasiewicz, Krystyna; Olejnik, Marian; Kalinowska, Iwona; Szawkało, Joanna; Czarnocki, Zbigniew

    2011-03-20

    This study examines the electron impact (EI) induced mass spectrometric behavior of several N,N-di-(β-arylisopropyl)formamides, which are connected to the Leuckart synthesis of some amphetamine analogues. Emphasis is laid on the fragmentation paths, which are common for all compounds under investigation and may be used in construction of the prediction scheme useful for identification of similar impurities, especially in absence of desirable authentic material. On the basis of this scheme several new N,N-di-(β-arylisopropyl)formamides have been identified in selected amphetamine analogues synthesized by the Leuckart method, including 4-methylthioamphetamine (4-MTA), 4-fluoroamphetamine (4-FA), 4-methylamphetamine, 3-trifluoromethylamphetamine, 3,4-methylenedioxyamphetamine (MDA), 2,5-dimethoxyamphetamine (2,5-DMA), 2,4,5- and 3,4,5-trimethoxyamphetamines (2-TMA and 3-TMA). PMID:20846801

  4. A Multivariate Assessment of Individual Differences in Sensation Seeking and Impulsivity as Predictors of Amphetamine Self-Administration and Prefrontal Dopamine Function in Rats

    OpenAIRE

    Marusich, Julie A.; Darna, Mahesh; Charnigo, Richard J; Dwoskin, Linda P.; Bardo, Michael T.

    2011-01-01

    Drug abuse vulnerability has been linked to sensation seeking (behaviors likely to produce rewards) and impulsivity (behaviors occurring without foresight). Since previous preclinical work has been limited primarily to using single tasks as predictor variables, the present study determined if measuring multiple tasks of sensation seeking and impulsivity would be useful in predicting amphetamine self-administration in rats. Multiple tasks were also used as predictor variables of dopamine trans...

  5. Long-Term Exposure to Oral Methylphenidate or dl-Amphetamine Mixture in Peri-Adolescent Rhesus Monkeys: Effects on Physiology, Behavior, and Dopamine System Development

    OpenAIRE

    Soto, Paul L.; Wilcox, Kristin M.; Zhou, Yun; Ator, Nancy A.; Riddle, Mark A.; Wong, Dean F.; Weed, Michael R.

    2012-01-01

    The stimulants methylphenidate and amphetamine are used to treat children with attention deficit/hyperactivity disorder over important developmental periods, prompting concerns regarding possible long-term health impact. This study assessed the effects of such a regimen in male, peri-adolescent rhesus monkeys on a variety of cognitive/behavioral, physiological, and in vivo neurochemical imaging parameters. Twice daily (0900 and 1200 hours), for a total of 18 months, juvenile male monkeys (8 p...

  6. Sensorimotor gating in NTS1 and NTS2 null mice: effects of d-amphetamine, dizocilpine, clozapine and NT69L

    OpenAIRE

    Oliveros, Alfredo; Michael G. Heckman; del Pilar Corena-McLeod, Maria; Williams, Katrina; Boules, Mona; Richelson, Elliott

    2010-01-01

    Pre-pulse inhibition (PPI) of the acoustic startle reflex is deficient in patients with schizophrenia. This deficiency is mimicked in mice by the use of the psychotomimetic drugs d-amphetamine and dizolcipine. Antipsychotic drugs such as clozapine are used to treat schizophrenic patients and are also administered to mice to prevent PPI disruption. Neurotensin (NT) produces antipsychotic-like effects when injected into rodent brain through its effects at NT subtype 1 (NTS1) and 2 (NTS2) recept...

  7. Inter-individual diversity and intra-individual stability of amphetamine-induced sensitization of frequency-modulated 50-kHz vocalization in Sprague–Dawley rats

    OpenAIRE

    Taracha, Ewa; Hamed, Adam; Krząścik, Paweł; Lehner, Małgorzata; Skórzewska, Anna; Płaźnik, Adam; Chrapusta, Stanisław J.

    2012-01-01

    Rationale Propensity for drug dependence shows great diversity that is related to intrinsic neurobiological factors. This diversity is important both for the understanding of these traits and for the development of therapies. Objectives The goals of the study were (1) to define, using ultrasonic vocalization characteristics, inter-individual differences in rats’ propensity for sensitization to amphetamine, (2) to test whether possible resistance to this effect could be overcome with repetitiv...

  8. Comparison of (+)-methamphetamine, ±}-methylenedioxymethamphetamine (MDMA), (+)-amphetamine and ±}-fenfluramine in rats on egocentric learning in the Cincinnati water maze

    OpenAIRE

    Vorhees, Charles V.; He, Elizabeth; Skelton, Matthew R.; Graham, Devon L.; Schaefer, Tori L.; Grace, Curtis E.; Braun, Amanda A.; Amos-Kroohs, Robyn; Williams, Michael T.

    2010-01-01

    (+)-Methamphetamine (MA), (±)-3,4-methylenedioxymethamphetamine (MDMA), (+)-amphetamine (AMPH), and (±)-fenfluramine (FEN) are phenylethylamines with CNS effects. At higher doses, each induces protracted reductions in brain dopamine and/or serotonin. Chronic MA and MDMA users show persistent monoamine reductions and cognitive impairments. In rats, similar neurochemical effects can be induced, yet cognitive impairments have been difficult to demonstrate. We recently showed that rats treated on...

  9. Development and validation of a single LC-MS/MS assay following SPE for simultaneous hair analysis of amphetamines, opiates, cocaine and metabolites.

    Science.gov (United States)

    Imbert, L; Dulaurent, S; Mercerolle, M; Morichon, J; Lachâtre, G; Gaulier, J-M

    2014-01-01

    The two major challenges in hair analysis are the limited amount of samples usually available and the low targeted concentrations. To overcome these limitations, a liquid chromatography-electrospray-tandem mass spectrometry method (LC-ESI-MS/MS) allowing the simultaneous analysis of 17 amphetamines (amphetamine, BDB, m-CPP, dexfenfluramine, DOB, DOM, ephedrine, MBDB, MDA, MDEA, MDMA, methamphetamine, methylphenidate, 4-MTA, norephedrine, norfenfluramine and PMA), 5 opiates (morphine, codeine, heroin, ethylmorphine, and 6AM), cocaine and 5 metabolites [ecgonine methyl ester (EME), benzoylecgonine (BZE), anhydroecgonine methyl ester (AME), cocaethylene, and norcocaine] has been developed. The validation procedure included linearity, intra-day and inter-day variability and accuracy for 5 days (5 replicates at 3 concentration levels). Proficiency studies were used to check the accuracy of the method. As a result, all amphetamines, opiates and cocaine derivatives were satisfactory identified by 2 MRM transitions in 15 min. Calibration curves were performed by a quadratic 1/X weighted regression. The calibration model fits from 0.05 to 10 ng/mg. The limits of detection (LODs) range between 0.005 and 0.030 ng/mg. Precision has been checked by intra-day and inter-day RSD, and associated relative bias, which were lower than 25% for the limits of quantifications (LOQs) and lower than 20% for the other levels tested. This method was routinely applied to hair samples: two positive results of adult drug addicts are presented. PMID:24378313

  10. Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants.

    Science.gov (United States)

    Miliano, Cristina; Serpelloni, Giovanni; Rimondo, Claudia; Mereu, Maddalena; Marti, Matteo; De Luca, Maria Antonietta

    2016-01-01

    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 [EMCDDA (European Drug Report), 2014; UNODC, 2014b; Trends and developments]. The chemical structure (phenethylamines, piperazines, 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%) (UNODC, 2014b). 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 analogs). Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ(9)-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 dependence associated

  11. 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

  12. Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants

    Science.gov (United States)

    Miliano, Cristina; Serpelloni, Giovanni; Rimondo, Claudia; Mereu, Maddalena; Marti, Matteo; De Luca, Maria Antonietta

    2016-01-01

    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 [EMCDDA (European Drug Report), 2014; UNODC, 2014b; Trends and developments]. The chemical structure (phenethylamines, piperazines, 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%) (UNODC, 2014b). 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 analogs). 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 dependence

  13. 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

  14. Development of a harmonised method for the profiling of amphetamines: III. Development of the gas chromatographic method.

    Science.gov (United States)

    Andersson, Kjell; Jalava, Kaisa; Lock, Eric; Finnon, Yvonne; Huizer, Henk; Kaa, Elisabet; Lopes, Alvaro; Poortman-van der Meer, Anneke; Cole, Michael D; Dahlén, Johan; Sippola, Erkki

    2007-06-14

    This study focused on gas chromatographic analysis of target compounds found in illicit amphetamine synthesised by the Leuckart reaction, reductive amination of benzyl methyl ketone, and the nitrostyrene route. The analytical method was investigated and optimised with respect to introduction of amphetamine samples into the gas chromatograph and separation and detection of the target substances. Sample introduction using split and splitless injection was tested at different injector temperatures, and their ability to transfer the target compounds to the GC column was evaluated using cold on column injection as a reference. Taking the results from both techniques into consideration a temperature of 250 degrees C was considered to be the best compromise. The most efficient separation was achieved with a DB-35MS capillary column (35% diphenyl 65% dimethyl silicone; 30 m x 0.25 mm, d(f) 0.25 microm) and an oven temperature program that started at 90 degrees C (1 min) and was increased by 8 degrees C/min to 300 degrees C (10 min). Reproducibility, repeatability, linearity, and limits of determination for the flame ionisation detector (FID), nitrogen phosphorous detector (NPD), and mass spectrometry (MS) in scan mode and selected ion monitoring (SIM) mode were evaluated. In addition, selectivity was studied applying FID and MS in both scan and SIM mode. It was found that reproducibility, repeatability, and limits of determination were similar for FID, NPD, and MS in scan mode. Moreover, the linearity was better when applying FID or NPD whereas the selectivity was better when utilising the MS. Finally, the introduction of target compounds to the GC column when applying injection volumes of 0.2 microl, 1 microl, 2 microl, and 4 microl with splitless injection respectively 1 microl with split injection (split ratio, 1:40) were compared. It was demonstrated that splitless injections of 1 microl, 2 microl, and 4 microl could be employed in the developed method, while split

  15. 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

  16. 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. PMID:26342055

  17. Temperature dependent changes in cocaine- and amphetamine regulated transcript (CART) peptide in the brain of tadpole, Sylvirana temporalis.

    Science.gov (United States)

    Shewale, Swapnil A; Gaupale, Tekchand C; Bhargava, Shobha

    2015-09-01

    Cocaine- and amphetamine-regulated transcript peptide (CARTp) has emerged as a novel neurotransmitter in the brain. Although the physiological role of the peptide has been intensely investigated in mammals, its role in amphibians has not been investigated. In the present study, an attempt has been undertaken to study the expression of CART in the tadpole brain of frog Sylvirana temporalis, subjected to thermal stress. Cells with strong CART-immunoreactivity were observed in the nucleus preoptic area (NPO) of tadpoles exposed to high temperature (37±2°C) as compared to those in the tadpoles exposed to low (12±2°C) and normal (24±2°C) temperatures. In the ventromedial thalamic nucleus (VM) and nucleus posterocentralis thalami (NPC), moderate CART-ir cells were observed in the control groups while number of cells and intensity of immunoreactivity was increased in tadpoles at low and high temperatures. In the nucleus infundibularis ventralis (NIV) and raphe nucleus (RA), CART immunoreactivity increased in the low as well as high temperature treated groups. Intensely stained CART cells were observed in the pituitary of tadpoles exposed to high temperature as compared to low temperature and control groups. We suggest that CART system in the brain and pituitary of tadpole may play a very important role in mediating responses to temperature variations in the environment. PMID:24983774

  18. Intrafollicular expression and potential regulatory role of cocaine- and amphetamine-regulated transcript in the ovine ovary.

    Science.gov (United States)

    Huang, Y; Yao, X L; Meng, J Z; Liu, Y; Jiang, X L; Chen, J W; Li, P F; Ren, Y S; Liu, W Z; Yao, J B; Folger, J K; Smith, G W; Lv, L H

    2016-01-01

    Follicular growth is regulated by a complex interaction of pituitary gonadotropins with local regulatory molecules. Previous studies demonstrated an important role for cocaine- and amphetamine-regulated transcript (CART) in regulation of granulosa cell estradiol production associated with dominant follicle selection in cattle. However, intraovarian expression and actions of CART in other species, including sheep, are not known. The objective of this study was to investigate the expression of CART in sheep follicles and determine the effects of CART on indices of ovine granulosa cell function linked to follicular development. Results demonstrated the expression of CART messenger RNA and prominent intraovarian localization of CART peptide in granulosa cells of sheep follicles. Granulosa cell CART messenger RNA was lower, but follicular fluid estradiol concentrations were higher in large (>5 mm) follicles vs smaller 3- to 5-mm follicles harvested from sheep ovaries of abattoir origin. CART treatment inhibited follicle stimulating hormone-induced estradiol production by cultured ovine granulosal cells and also blocked the follicle stimulating hormone-induced increase in granulosa cell numbers. Results demonstrate expression of CART in sheep follicular tissues and suggest potential biological actions of CART, which are inhibitory to ovine follicular growth and development. PMID:26490113

  19. Replacing immunoassays for mephedrone, ketamines and six amphetamine-type stimulants with flow injection analysis tandem mass spectrometry.

    Science.gov (United States)

    Lua, Ingrid A; Lin, Shiou-Ling; Lin, Huei R; Lua, Ahai C

    2012-10-01

    A screening procedure was developed for the simultaneous detection of mephedrone, six amphetamine-type stimulants (ATS), ketamine and its two metabolites with electrospray ionization flow injection analysis tandem mass spectrometry (FIA-MS-MS). Urine samples were fortified with deuterated analogues as internal standards, extracted with ethyl acetate and analyzed with FIA-MS-MS. The mass analyzer was operated in multiple reaction monitoring mode. Two product ions were monitored for each drug and internal standards. For each analyte, the limit of detection was less than 4 µg/L, within-day and between-day precisions (percent coefficient of variation) at three different concentrations were less than 7.3% and bias was between -17.3 and 11.8%. Total analysis time with FIA-MS-MS is 1.8 min per sample. A group of 215 urine samples were screened with immunoassay for ATS and analyzed with FIA-MS-MS and gas chromatography-mass spectrometry (GC-MS) for ketamines and ATS. The analysis of ATS by immunoassay and GC-MS was 96.7% concordant. The analysis of three ketamines and seven ATS by FIA-MS-MS and GC-MS was 97.2% concordant. The FIA-MS-MS procedure is efficient, accurate, flexible and capable of detecting analytes of different chemical groups. It can replace immunoassays for the screening of new designer drugs when commercial immunoassays are unavailable. PMID:22933658

  20. The polymorphisms of bovine cocaine- and amphetamine-regulated transcripts and their associations with cattle (Bos taurus) growth traits

    Indian Academy of Sciences (India)

    Chun Lei Zhang; Hong Chen; Yan Hong Wang; Xian Yong Lan; Chu Zhao Lei; Xing Tang Fang

    2008-09-01

    We investigated the polymorphisms of bovine cocaine- and amphetamine-regulated transcripts (CART). The coding and regulating regions of CART were screened in 7 cattle breeds by the single-stranded conformation polymorphism (SSCP) technique. The four loci (C1, C2, C3 and C4) studied were all polymorphic. Polymerase chain reaction (PCR) products representing different SSCP variants were sequenced and a total of 9 single-nucleotide polymorphisms (SNPs) were found. The associations between polymorphic loci and the growth traits of Nanyang cattle were analysed. The results indicated that genotype A1A1 of the C1 locus was associated with a higher body weight ( < 0.05) than heterozygous A1B1. Genotype A2A2 of the C2 locus was associated with lower body weight and average daily weight gain ( ≤ 0.001) than heterozygous A2B2. C3 and C4 loci had no significant effect on Nanyang cattle growth traits (P > 0.05).

  1. A cocaine-regulated and amphetamine-regulated transcript inhibits oxidative stress in neurons deprived of oxygen and glucose.

    Science.gov (United States)

    Sha, Dujuan; Wang, Zhongyuan; Qian, Lai; Han, Yong; Zhang, Jun; Gu, Shuangshuang; Wang, Luna; Li, Jie; Chen, Cong; Xu, Yun

    2013-09-11

    Stroke, of which about 87% is ischemic stroke, constitutes one of the main causes of morbidity, disability, and mortality worldwide. Ischemic brain injury has complex pathological mechanisms. Considerable evidence has been collected over the last few years suggesting that oxidative stress associated with excessive production of reactive oxygen species is a fundamental mechanism of brain damage in stroke and reperfusion after stroke. Oxidative stress is an important trigger of neuronal apoptosis in ischemic stroke. In this current study, it was found that cocaine-regulated and amphetamine-regulated transcript 55-102 (CART55-102) inhibited oxygen-induced and glucose deprivation (OGD)-induced neurotoxicity in a dose-dependent manner. The peak dose of CART55-102 was 0.4 nmol/l. In addition, the level of intracellular reactive oxygen species was decreased in OGD-treated neurons in the presence of 0.4 nmol/l CART55-102. Mitochondrial membrane potential (ΔΨm) and mtDNA mRNA expressions were increased in OGD-treated neurons in the presence of 0.4 nmol/l CART55-102. The current study suggests that CART55-102, by inhibiting oxidative stress, may be developed into therapeutic agents for ischemic stroke. PMID:23884173

  2. Cocaine- and amphetamine-regulated transcript: a novel regulator of energy homeostasis expressed in a subpopulation of pancreatic islet cells.

    Science.gov (United States)

    Gilon, Patrick

    2016-09-01

    Type 2 diabetes is characterised by chronic hyperglycaemia and its incidence is highly increased by exaggerated food consumption. It results from a lack of insulin action/production, but growing evidence suggests that it might also involve hyperglucagonaemia and impaired control of glucose homeostasis by the brain. In recent years, the cocaine and amphetamine-regulated transcript (CART) peptides have generated a lot of interest in the battle against obesity because, via the brain, they exert anorexic effects and they increase energy expenditure. They are also localised, outside the brain, in discrete regions of the body and play a hormonal role in controlling various functions. In this issue of Diabetologia, the Wierup group (doi: 10.1007/s00125-016-4020-6 ) shows that CART peptides are expressed heterogeneously in islet cells of various species, including humans, and that their expression is upregulated in diabetes. The authors also shine a spotlight on some interesting effects of CART peptides on islet function, including stimulation of insulin secretion and inhibition of glucagon release. CART peptides would thus be at the centre of a cooperation between the brain and the endocrine pancreas to control glucose homeostasis. Although the mechanisms of action of CART peptides remain enigmatic because no specific receptor for these peptides has so far been discovered, their potential therapeutic use is evident and represents a new challenge for future research. PMID:27421727

  3. Role of oxidative stress in disrupting the function of negative glucocorticoid response element in daily amphetamine-treated rats.

    Science.gov (United States)

    Chu, Shu-Chen; Yu, Ching-Han; Chen, Pei-Ni; Hsieh, Yih-Shou; Kuo, Dong-Yih

    2016-09-01

    Amphetamine (AMPH)-induced appetite suppression is associated with changes in hypothalamic reactive oxygen species (ROS), antioxidants, neuropeptides, and plasma glucocorticoid. This study explored whether ROS and glucocorticoid response element (GRE), which is the promoter site of corticotropin-releasing hormone (CRH) gene, participated in neuropeptides-mediated appetite control. Rats were treated daily with AMPH for four days, and changes in food intake, plasma glucocorticoid and expression levels of hypothalamic neuropeptide Y (NPY), proopiomelanocortin (POMC), superoxide dismutase (SOD), CRH, and glucocorticoid receptor (GR) were examined and compared. Results showed that food intake decreased and NPY gene down-regulated, while POMC, SOD, and CRH gene up-regulated during AMPH treatment. GR and GRE-DNA bindings were disrupted on Day 1 and Day 2 when glucocorticoid levels were still high. Pretreatment with GR inhibitor or ROS scavenger modulated mRNA levels in NPY, POMC, SOD and CRH in AMPH-treated rats. We suggest that disruptions of negative GRE (nGRE) on Day 1 and Day 2 are associated with an increase in oxidative stress during the regulation of NPY/POMC-mediated appetite control in AMPH-treated rats. These results advance the understanding of molecular mechanism in regulating AMPH-mediated appetite suppression. PMID:27235634

  4. Simultaneous determination of methamphetamine and its metabolite, amphetamine, in urine using a high performance liquid chromatography column-switching method.

    Science.gov (United States)

    Kumihashi, Mitsuru; Ameno, Kiyoshi; Shibayama, Takayuki; Suga, Keisuke; Miyauchi, Hiroshi; Jamal, Mostofa; Wang, Weihuan; Uekita, Ikuo; Ijiri, Iwao

    2007-01-01

    We describe here a simple, precise, and highly sensitive method for the simultaneous determination of methamphetamine (MA) and amphetamine (AM) in urine using a high performance liquid chromatography (HPLC) column-switching method. A PK-2A (Shodex) column was used for extraction and deproteinization, and a CAPCELL PAK SCX semi-micro, polymer-coated cation-exchange column was employed for separation. The urine sample was mixed with an equal volume of borate buffer (0.1M, pH 9.4), and then 100 microl of the mixture was injected into the HPLC column. The column was switched for 6 min, and then 10 min later detection was performed at 210 nm. Recovery yields of the MA and AM spiked in the urine were 93.0-100.4% with a coefficient of variation of less than 1%. The calibration curves of MA and AM were in the range of 0.1-10 microg/ml with good linearity (r(2)=0.999), with the limit of qualification being 0.005 microg/ml. This method of using HPLC with column-switching can be used for both qualification and quantification of MA and its metabolite, AM, in urine, especially in forensic cases. PMID:16916628

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

    International Nuclear Information System (INIS)

    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.

  6. 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

  7. 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. PMID:26026487

  8. Colocalization of cocaine- and amphetamine-regulated transcript with kisspeptin and neurokinin B in the human infundibular region.

    Directory of Open Access Journals (Sweden)

    Katalin Skrapits

    Full Text Available Kisspeptin (KP- and neurokinin B (NKB- synthesizing neurons of the hypothalamic arcuate nucleus play a pivotal role in the regulation of pulsatile gonadotropin-releasing hormone (GnRH secretion. Unlike in rodents and sheep, the homologous KP and NKB neurons in the human infundibular region rarely express dynorphin- but often exhibit Substance P (SP immunoreactivity, indicating remarkable species differences in the neurochemical phenotype of these neurons. In search for additional neuropeptides in human KP and NKB neurons, we carried out immunofluorescent studies on hypothalamic sections obtained from five postmenopausal women. Colocalization experiments provided evidence for the presence of cocaine- and amphetamine-regulated transcript (CART in 47.9 ± 6.6% of KP-immunoreactive (IR and 30.0 ± 4.9% of NKB-IR perikarya and in 17.0 ± 2.3% of KP-IR and 6.2 ± 2.0% of NKB-IR axon varicosities. All three neuropeptides were present in 33.3 ± 4.9% of KP-IR and 28.2 ± 4.6% of NKB-IR somata, respectively, whereas triple-labeling showed lower incidences in KP-IR (14.3 ± 1.8% and NKB-IR (5.9 ± 2.0% axon varicosities. CART-IR KP and NKB neurons established contacts with other peptidergic cells, including GnRH-IR neurons and also sent projections to the infundibular stalk. KP and NKB fibers with CART often contained SP as well, while being distinct from CART fibers co-containing the orexigenic peptide agouti-related protein. Presence of CART in human, but not rodent, KP and NKB neurons represents a new example of species differences in the neuropeptide repertoire of mediobasal hypothalamic KP and NKB neurons. Target cells, receptor sites and physiological significance of CART in the efferent communication of KP and NKB neurons in primates require clarification.

  9. NMDA receptors are involved in the antidepressant-like effects of capsaicin following amphetamine withdrawal in male mice.

    Science.gov (United States)

    Amiri, Shayan; Alijanpour, Sakineh; Tirgar, Fatemeh; Haj-Mirzaian, Arya; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Rastegar, Mojgan; Ghaderi, Marzieh; Ghazi-Khansari, Mahmoud; Zarrindast, Mohammad-Reza

    2016-08-01

    Amphetamine withdrawal (AW) is accompanied by diminished pleasure and depression which plays a key role in drug relapse and addictive behaviors. There is no efficient treatment for AW-induced depression and underpinning mechanisms were not well determined. Considering both transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and N-Methyl-d-aspartate (NMDA) receptors contribute to pathophysiology of mood and addictive disorders, in this study, we investigated the role of TRPV1 and NMDA receptors in mediating depressive-like behaviors following AW in male mice. Results revealed that administration of capsaicin, TRPV1 agonist, (100μg/mouse, i.c.v.) and MK-801, NMDA receptor antagonist (0.005mg/kg, i.p.) reversed AW-induced depressive-like behaviors in forced swimming test (FST) and splash test with no effect on animals' locomotion. Co-administration of sub-effective doses of MK-801 (0.001mg/kg, i.p.) and capsaicin (10μg/mouse, i.c.v) exerted antidepressant-like effects in behavioral tests. Capsazepine, TRPV1 antagonist, (100μg/mouse, i.c.v) and NMDA, NMDA receptor agonist (7.5mg/kg, i.p.) abolished the effects of capsaicin and MK-801, respectively. None of aforementioned treatments had any effect on behavior of control animals. Collectively, our findings showed that activation of TRPV1 and blockade of NMDA receptors produced antidepressant-like effects in male mice following AW, and these receptors are involved in AW-induced depressive-like behaviors. Further, we found that rapid antidepressant-like effects of capsaicin in FST and splash test are partly mediated by NMDA receptors. PMID:27167081

  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

    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

  11. Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring.

    Science.gov (United States)

    Batinić, Bojan; Santrač, Anja; Divović, Branka; Timić, Tamara; Stanković, Tamara; Obradović, Aleksandar Lj; Joksimović, Srđan; Savić, Miroslav M

    2016-02-15

    Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100 μg/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-α and IL-6 in dam blood withdrawn 2h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively. PMID:26620494

  12. Blockade of the locomotor stimulant effects of amphetamine by group I, group II, and group III metabotropic glutamate receptor ligands in the rat nucleus accumbens: possible interactions with dopamine receptors.

    Science.gov (United States)

    David, H N; Abraini, J H

    2003-05-01

    Previous investigations have shown that mGlu receptors would be involved in the amphetamine-induced motor response. However, data are somewhat controversial across studies where methodological protocols vary. The aim of the present study was to determine the involvement of mGlu receptors in the NAcc in the locomotor-activating properties of amphetamine in rats well habituated to their experimental environment, a condition known to modulate the motor response to amphetamine. Focal infusion of the group I mGlu receptor antagonist S-4-CPG, which has no effect on basal motor activity, virtually suppressed the locomotor response to amphetamine, while infusion of the group II mGlu receptor antagonist LY 341495 or the group III mGlu receptor agonist AP4, at the minimal dose that produces locomotor activation, reduced it by approximately a half. These effects were blocked by the group I mGlu receptor agonist DHPG, the group II mGlu receptor agonist APDC, and the group III mGlu receptor antagonist MPPG, respectively. These data confirm that mGlu receptors in the NAcc contribute to the psychostimulant motor effect of amphetamine. Results are discussed from the view of recent neuropharmacological studies that have defined the effects of these mGlu receptor ligands on basal motor activity and DA receptor agonists-induced locomotor responses in rats exposed to similar experimental procedures (Eur J Neuroscience 13 (2001) 2157; Neuropharmacology 41 (2001) 454; Eur J Neuroscience 13 (2001) 869). It is suggested that the contribution of mGlu receptors to the amphetamine-induced motor response may result mainly from their functional, either direct or indirect, interactions with D1-like receptors in the NAcc. PMID:12681370

  13. Absence of the GPR37/PAEL receptor impairs striatal Akt and ERK2 phosphorylation, DeltaFosB expression, and conditioned place preference to amphetamine and cocaine.

    Science.gov (United States)

    Marazziti, Daniela; Di Pietro, Chiara; Mandillo, Silvia; Golini, Elisabetta; Matteoni, Rafaele; Tocchini-Valentini, Glauco P

    2011-06-01

    The orphan G-protein-coupled receptor 37 (GPR37) colocalizes with the dopamine (DA) transporter (DAT) in mouse nigrostriatal presynaptic membranes, and its genetic ablation in homozygous null-mutant (GPR37-KO) mice provokes the marked increase of plasma membrane expression of DAT, alteration of psychostimulant-induced locomotor activity, and reduction of catalepsy induced by DA-receptor antagonists. We report that extracts from GPR37-KO mice displayed biochemical alterations of the nigrostriatal signaling pathways mediated by D1 and D2 dopaminergic receptors. Null-mutant mice showed an increase of the basal phosphorylation level of the D2-regulated Akt kinase. The basal phosphorylation of the D1-activated ERK2 kinase was not altered, but acute treatments with amphetamine or cocaine failed to produce its specific increase, as detected in samples from wild-type littermates. Furthermore, the chronic administration of cocaine to GPR37-KO mice did not increase the expression of the ΔFosB transcription factor isoforms. Consistently, behavioral analysis showed that null-mutant animals did not respond to the incentive properties of amphetamine or cocaine, in conditioned place preference tests. Thus, the lack of GPR37 affects both ERK2- and Akt-mediated striatal signaling pathways, impairing the biochemical and behavioral responses typically induced by acute and chronic administration of psychostimulant drugs. PMID:21372109

  14. D-amphetamine improves attention performance in adolescent Wistar, but not in SHR rats, in a two-choice visual discrimination task.

    Science.gov (United States)

    Bizot, Jean-Charles; Cogrel, Nicolas; Massé, Fabienne; Chauvin, Virgile; Brault, Léa; David, Sabrina; Trovero, Fabrice

    2015-09-01

    The validity of spontaneous hypertensive rat (SHR) as a model of attention deficit hyperactivity disorder (ADHD) has been explored by comparing SHR with Wistar rats in a test of attention, the two-choice visual discrimination task (2-CVDT). Animals were 4-5 weeks old during the training phase of the experiment and 6-7 weeks old during the testing phase in which they were tested with D-amphetamine, a stimulant drug used for the treatment of ADHD. As compared to Wistar, SHR showed a slightly better attention performance, a slightly lower impulsivity level, and a lower general activity during the training phase, but these differences disappeared or lessened thereafter, during the testing phase. D-amphetamine (0.5, 1 mg/kg) improved attention performance in Wistar, but not in SHR, and did not modify impulsivity and activity in the two strains. In conclusion, the present study did not demonstrate that SHR represents a valid model of ADHD, since it did not show face validity regarding the behavioral symptoms of ADHD and predictive validity regarding the effect of a compound used for the treatment of ADHD. On the other hand, this study showed that the 2-CVDT may represent a suitable tool for evaluating in adolescent Wistar rats the effect on attention of compounds intended for the treatment of ADHD. PMID:26037943

  15. 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

    2016-03-01

    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. PMID:25847603

  16. A review of impurity profiling and synthetic route of manufacture of methylamphetamine, 3,4-methylenedioxymethylamphetamine, amphetamine, dimethylamphetamine and p-methoxyamphetamine.

    Science.gov (United States)

    Stojanovska, Natasha; Fu, Shanlin; Tahtouh, Mark; Kelly, Tamsin; Beavis, Alison; Kirkbride, K Paul

    2013-01-10

    Amphetamine-type substances (ATS), like other synthetically derived compounds, can be produced by a multitude of synthetic pathways using a variety of precursors and reagents, resulting in a large number of possible contaminants (by-products, intermediates and impurities). This review article describes the common contaminants found in preparations of methylamphetamine (MA), 3,4-methylenedioxymethylamphetamine (MDMA), amphetamine (AP), N,N-dimethylamphetamine (DMA) and p-methoxyamphetamine (PMA) synthesised via common synthetic pathways including reductive amination, Leuckart method, Nagai method, Emde method, Birch reduction, "Moscow" method, Wacker process, "Nitrostyrene" method and the Peracid oxidation method. Contaminants can facilitate identification of the synthetic route, origin of precursors and may suggest information as to the location of manufacture of these illicit drugs. Contaminant profiling can provide vital intelligence for investigations in which linking seizures or identifying the synthetic pathway is essential. This review article presents an accessible resource; a compilation of contaminants resulting from a variety of manufacturing methods used to synthesise the most common ATS. It is important for research in this field to continue as valuable information can be extracted from illicit drug samples, increasing discrimination amongst ATS, and in turn, leading to an increase in evidential value and forensic drug intelligence from forensic drug samples. PMID:23182870

  17. Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

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    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

  18. The effect of the substituted amphetamines, 2.4-methylenedioxymethamphetamine (MDMA) and P-methoxyamphetamine (PMA), on platelet aggregation

    International Nuclear Information System (INIS)

    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 5HT2 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 14C-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

  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

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    Nga Thi Thu Vu

    2015-02-01

    Full Text Available 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

  20. 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.)

  1. The effects of d-amphetamine on extrastriatal dopamine D2/D3 receptors: a randomized, double-blind, placebo-controlled PET study with [11C]FLB 457 in healthy subjects

    International Nuclear Information System (INIS)

    The dopamine D2/D3 receptor ligand [11C]FLB 457 and PET enable quantification of low-density extrastriatal D2/D3 receptors, but it is uncertain whether [11C]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 [11C]FLB 457 binding potential (BPND) in a randomized, double-blind, placebo-controlled study including 24 healthy volunteers. The effects of d-amphetamine on [11C]FLB 457 BPND and distribution volume (VT) in the frontal cortex were not different from those of placebo. Small decreases in [11C]FLB 457 BPND were observed only in the posterior cingulate and hippocampus. The regional changes in [11C]FLB 457 BPND 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 D2/D3 receptor binding. Our results indicate that [11C]FLB 457 PET is not a useful method for measuring extrastriatal dopamine release in humans. (orig.)

  2. Dextroamphetamine and Amphetamine

    Science.gov (United States)

    ... for ADHD, which may include counseling and special education. Make sure to follow all of your doctor's ... numbness of an arm or leg seizures motor tics or verbal tics believing things that are not ...

  3. Substance use -- amphetamines

    Science.gov (United States)

    ... get through daily life. Addiction can lead to tolerance. Tolerance means you need more and more of the ... PhD, and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Club Drugs Methamphetamine Browse ...

  4. 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)

    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-NO2) and poly(p-aminostyrene)-coated silica (SG-PS-NH2), 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.

  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. 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. PMID:26650252

  7. Anticonvulsant medications attenuate amphetamine-induced deficits in behavioral inhibition but not decision making under risk on a rat gambling task.

    Science.gov (United States)

    Tremblay, Melanie; Winstanley, Catharine A

    2016-11-01

    Impulsivity is a major component of mania in bipolar disorder (BD), and patients also show impairments in decision-making involving risk on the Iowa Gambling Task (IGT). Similar deficits are observed in some patients with temporal lobe epilepsy (TLE), and incidence of problem gambling is higher in both these populations. Anticonvulsant drugs are widely used in the treatment of epilepsy, but also as mood stabilizers and prophylaxis for the management of BD. Unfortunately, little is still known about the precise mechanisms of action underlying their efficacy, and the specific behavioral aspect targeted by these drugs. This project explored the effect of the three anticonvulsant drugs currently also used as mood stabilizers- carbamazepine, valproate and lamotrigine on aspects of decision-making using a rat analogue of the IGT, the rat Gambling Task (rGT). In this task, rats choose between four distinct, probabilistic reinforcement schedules. Sugar pellet profits are maximized by adopting a conservative strategy, avoiding tempting high-risk, high-reward options. Effects of the anticonvulsant agents were assessed on baseline performance and also in conjunction with amphetamine administration, in order to approximate a "mania-like" state. Carbamazepine appeared to slow processing speed, decreasing premature responses and increasing choice latency, whereas valproate and lamotrigine had no effect. When administered prior to amphetamine, lamotrigine was the only drug that failed to attenuate the pro-impulsive effect of the psychostimulant. Further studies looking at chronic administration of anticonvulsants may help us understand the impact of this medication class on decision-making and impulsivity in healthy rats and disease models. PMID:27515288

  8. D1 receptor-mediated inhibition of medial prefrontal cortex neurons is disrupted in adult rats exposed to amphetamine in adolescence.

    Science.gov (United States)

    Kang, S; Paul, K; Hankosky, E R; Cox, C L; Gulley, J M

    2016-06-01

    Amphetamine (AMPH) exposure leads to changes in behavior and dopamine receptor function in the prefrontal cortex (PFC). Since dopamine plays an important role in regulating GABAergic transmission in the PFC, we investigated if AMPH exposure induces long-lasting changes in dopamine's ability to modulate inhibitory transmission in the PFC as well as whether the effects of AMPH differed depending on the age of exposure. Male Sprague-Dawley rats were given saline or 3mg/kg AMPH (i.p.) repeatedly during adolescence or adulthood and following a withdrawal period of up to 5weeks (Experiment 1) or up to 14weeks (Experiment 2), they were sacrificed for in vitro whole-cell recordings in layer V/VI of the medial PFC. We found that in brain slices from either adolescent- or adult-exposed rats, there was an attenuation of dopamine-induced increases in inhibitory synaptic currents in pyramidal cells. These effects did not depend on age of exposure, were mediated at least partially by a reduced sensitivity of D1 receptors in AMPH-treated rats, and were associated with an enhanced behavioral response to the drug in a separate group of rats given an AMPH challenge following the longest withdrawal period. Together, these data reveal a prolonged effect of AMPH exposure on medial PFC function that persisted for up to 14weeks in adolescent-exposed animals. These long-lasting neurophysiological changes may be a contributing mechanism to the behavioral consequences that have been observed in those with a history of amphetamine abuse. PMID:26946269

  9. Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT1A receptor knockout mice: Implications for schizophrenia

    OpenAIRE

    van den Buuse, Maarten; Ruimschotel, Emma; Martin, Sally; Risbrough, Victoria B.; Halberstadt, Adam L.

    2011-01-01

    Serotonin-1A (5-HT1A) receptors may play a role in schizophrenia and the effects of certain antipsychotic drugs. However, the mechanism of interaction of 5-HT1A receptors with brain systems involved in schizophrenia, remains unclear. Here we show that 5-HT1A receptor knockout mice display enhanced locomotor hyperactivity to acute treatment with amphetamine, a widely used animal model of hyperdopaminergic mechanisms in psychosis. In contrast, the effect of MK-801 on locomotor activity, modelin...

  10. Evaluation of Genetic Variability in the Dopamine Receptor D2 in Relation to Behavioral Inhibition and Impulsivity/Sensation Seeking: An Exploratory Study With d-Amphetamine in Healthy Participants

    OpenAIRE

    Hamidovic, Ajna; Dlugos, Andrea; Skol, Andrew; Palmer, Abraham A.; de Wit, Harriet

    2009-01-01

    The dopamine D2 receptor (DRD2) appears to be involved in impulsive behaviors, and particularly in behavioral inhibition. We sought to determine whether inhibition and impulsivity were related to genetic polymorphisms in the DRD2 gene (DRD2) in healthy volunteers (N = 93). Participants received placebo or d-amphetamine in random order. They performed the stop task, measuring behavioral inhibition, and rated their mood states on each session. They also completed the Zuckerman–Kuhlman Personali...

  11. Effects of d-amphetamine, WIN 35,428, pentobarbital and morphine on schedule-controlled responding in two inbred rat strains that differ in locomotor stimulatory effects of cocaine.

    Science.gov (United States)

    Witkin, J.M.; Goldberg, S.R.

    1992-10-01

    Behavioral effects of d-amphetamine, the cocaine analog, WIN 35,428, morphine, and pentobarbital were compared in NBR/NIH and F344CR1BR rats. Either nose-poke or lever-press responding was maintained under 3-min fixed-interval schedules of food presentation. The effects of morphine, WIN 35,428 and pentobarbital depended upon the rat strain studied: morphine increased nose-poke responding in NBR but not F344 rats; significant strain x dose interactions were observed with WIN 35,428; and pentobarbital was more potent in decreasing nose-poke responding in NBR than in F344 rats. No strain differences were observed in the behavioral effects of d-amphetamine. There were also prominent differences in the effects of drugs that were related to the nature of the response requirement. In both rat strains, nose-poke responding was affected differently than lever-press responding by morphine, d-amphetamine, and WIN 35,428. Pentobarbital produced effects that were independent of the specified response topography. A global underlying difference in these rat strains cannot be identified at present to account for the diversity of findings. The behavioral effects of these drugs appear to be influenced by a host of interactive factors including the drug, strain of animal, the baseline response rate and physical dimensions of the response. PMID:11224148

  12. Uso de álcool e anfetaminas entre caminhoneiros de estrada Alcohol and amphetamines use among long-distance truck drivers

    Directory of Open Access Journals (Sweden)

    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. 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. PMID:25010400

  14. Assessing addiction vulnerability with different rat strains and place preference procedures: the role of the cocaine and amphetamine-regulated transcript.

    Science.gov (United States)

    Salas, Elisabet; Bocos, Carlos; Castillo, Carmen Del; Pérez-García, Carmen; Morales, Lidia; Alguacil, Luis F

    2013-09-01

    Validated biomarkers of addiction vulnerability are unavailable despite their potential value in diagnostics and therapeutics. As cocaine and amphetamine-regulated transcript (CART) peptides can be considered candidates for such biomarkers, we have studied the acute regulation of CART gene expression in the nucleus accumbens of rats with different drug-seeking behaviors. Two subgroups of Sprague-Dawley rats with different persistences of cocaine-induced and morphine-induced place preference showed a similar regulation of CART mRNA irrespective of their behavioral differences: CART gene expression was unaffected by acute cocaine and downregulated by acute morphine to a similar extent in both subgroups. Fischer 344 and Lewis rats, known to exhibit very different drug-seeking behaviors, showed lower basal expression of CART when compared with Sprague-Dawley rats, being almost undetectable in the case of the Lewis strain. Acute morphine downregulated CART in Fischer 344 rats as it did in Sprague-Dawley rats. The results tend to show that CART mRNA regulation by acute morphine or cocaine in the nucleus accumbens does not seem predictive of addiction vulnerability. However, in the particular case of Lewis rats, the pronounced hypoactivity of the CART system could contribute to the high vulnerability of this strain to develop drug-seeking behaviors. PMID:23907376

  15. Amphetamine-induced sensitization has little effect on multiple learning paradigms and fails to rescue mice with a striatal learning defect.

    Directory of Open Access Journals (Sweden)

    Kiara C Eldred

    Full Text Available Behavioral sensitization to psychostimulants such as amphetamine (AMPH is associated with synaptic modifications that are thought to underlie learning and memory. Because AMPH enhances extracellular dopamine in the striatum where dopamine and glutamate signaling are essential for learning, one might expect that the molecular and morphological changes that occur in the striatum in response to AMPH, including changes in synaptic plasticity, would affect learning. To ascertain whether AMPH sensitization affects learning, we tested wild-type mice and mice lacking NMDA receptor signaling in striatal medium spiny neurons in several different learning tests (motor learning, Pavlovian association, U-maze escape test with strategy shifting with or without prior sensitization to AMPH. Prior sensitization had minimal effect on learning in any of these paradigms in wild-type mice and failed to restore learning in mutant mice, despite the fact that the mutant mice became sensitized by the AMPH treatment. We conclude that the changes in synaptic plasticity and many other signaling events that occur in response to AMPH sensitization are dissociable from those involved in learning the tasks used in our experiments.

  16. Leptin-Induced CART (Cocaine- and Amphetamine-Regulated Transcript) Is a Novel Intraovarian Mediator of Obesity-Related Infertility in Females.

    Science.gov (United States)

    Ma, Xiaoting; Hayes, Emily; Prizant, Hen; Srivastava, Rajesh K; Hammes, Stephen R; Sen, Aritro

    2016-03-01

    Obesity is considered detrimental to women's reproductive health. Although most of the attention has been focused on the effects of obesity on hypothalamic function, studies suggest a multifactorial impact. In fact, obesity is associated with reduced fecundity even in women with regular cycles, indicating that there may be local ovarian effects modulating fertility. Here we describe a novel mechanism for leptin actions directly in the ovary that may account for some of the negative effects of obesity on ovarian function. We find that normal cycling, obese, hyperleptinemic mice fed with a high-fat diet are subfertile and ovulate fewer oocytes compared with animals fed with a normal diet. Importantly, we show that leptin induces expression of the neuropeptide cocaine- and amphetamine-regulated transcript (CART) in the granulosa cells (GCs) of ovarian follicles both in vitro and in vivo. CART then negatively affects intracellular cAMP levels, MAPK signaling, and aromatase mRNA expression, which leads to lower estradiol synthesis in GCs and altered ovarian folliculogenesis. Finally, in human samples from patients undergoing in vitro fertilization, we show a significant positive correlation between patient body mass index, CART mRNA expression in GCs, and CART peptide levels in follicular fluid. These observations suggest that, under obese conditions, CART acts as a local mediator of leptin in the ovary to cause ovarian dysfunction and reduced fertility. PMID:26730935

  17. Prenatal immune challenge in rats: effects of polyinosinic-polycytidylic acid on spatial learning, prepulse inhibition, conditioned fear, and responses to MK-801 and amphetamine.

    Science.gov (United States)

    Vorhees, Charles V; Graham, Devon L; Braun, Amanda A; Schaefer, Tori L; Skelton, Matthew R; Richtand, Neil M; Williams, Michael T

    2015-01-01

    Prenatal maternal immune activation increases risk for schizophrenia and/or autism. Previous data suggest that maternal weight change in response to the immune activator polyinosinic-polycytidylic (Poly IC) in rats influences the severity of effect in the offspring as does the exposure period. We treated gravid Sprague-Dawley rats from E14 to 18 with 8mg/kg/day Poly IC or saline. The Poly IC group was divided into those that gained the least weight or lost (Poly IC (L)) and those that gained the most (Poly IC (H)) weight. There were no effects of Poly IC on anxiety (elevated zero-maze, open-field, object burying), or Morris water maze cued learning or working memory or Cincinnati water maze egocentric learning. The Poly IC (H) group males had decreased acoustic startle whereas Poly IC (L) females had reduced startle and increased PPI. Poly IC offspring showed exaggerated hyperactivity in response to amphetamine (primarily in the Poly IC (H) group) and attenuated hyperactivity in response to MK-801 challenge (primarily in the Poly IC (L) group). Poly IC (L) males showed reduced cued conditioned freezing; both sexes showed less time in the dark in a light-dark test, and the Poly IC groups showed impaired Morris water maze hidden platform acquisition and probe performance. The data demonstrate that offspring from the most affected dams were more affected than those from less reactive dams indicating that degree of maternal immune activation predicts severity of effects on offspring behavior. PMID:25450663

  18. Cocaine- and amphetamine-regulated transcript peptide (CART) in the brain of zebra finch, Taeniopygia guttata: Organization, interaction with neuropeptide Y, and response to changes in energy status.

    Science.gov (United States)

    Singh, Omprakash; Kumar, Santosh; Singh, Uday; Kumar, Vinod; Lechan, Ronald M; Singru, Praful S

    2016-10-15

    Cocaine- and amphetamine-regulated transcript (CART) has emerged as a potent anorectic agent. CART is widely distributed in the brain of mammals, amphibians, and teleosts, but the relevant information in avian brain is not available. In birds, CART inhibits food intake, whereas neuropeptide Y (NPY), a well-known orexigenic peptide, stimulates it. How these neuropeptides interact in the brain to regulate energy balance is not known. We studied the distribution of CART-immunoreactivity in the brain of zebra finch, Taeniopygia guttata, its interaction with NPY, and their response to dynamic energy states. CART-immunoreactive fibers were found in the subpallium, hypothalamus, midbrain, and brainstem. Conspicuous CART-immunoreactive cells were observed in the bed nucleus of the stria terminalis, hypothalamic paraventricular, supraoptic, dorsomedial, infundibular (IN), lateral hypothalamic, Edinger-Westphal, and parabrachial nuclei. Hypothalamic sections of fed, fasted, and refed animals were immunostained with cFos, NPY, and CART antisera. Fasting dramatically increased cFos- and NPY-immunoreactivity in the IN, followed by rapid reduction by 2 hours and restoration to normal fed levels 6-10 hours after refeeding. CART-immunoreactive fibers in IN showed a significant reduction during fasting and upregulation with refeeding. Within the IN, double immunofluorescence revealed that 94 ± 2.1% of NPY-immunoreactive neurons were contacted by CART-immunoreactive fibers and 96 ± 2.8% NPY-immunoreactive neurons expressed cFos during fasting. Compared to controls, superfused hypothalamic slices of fasted birds treated with CART-peptide showed a significant reduction (P brain of T. guttata may perform several functions, and has a particularly important role in the hypothalamic regulation of energy homeostasis. J. Comp. Neurol. 524:3014-3041, 2016. © 2016 Wiley Periodicals, Inc. PMID:27018984

  19. ELECTROPHYSIOLOGICAL CHARACTERISTICS OF PARAVENTRICULAR THALAMIC (PVT NEURONS IN RESPONSE TO CHRONIC COCAINE EXPOSURE: EFFECTS OF COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT (CART

    Directory of Open Access Journals (Sweden)

    Jiann Wei Yeoh

    2014-08-01

    Full Text Available Recent work has established that the paraventricular thalamus (PVT is a central node in the brain reward-seeking pathway. This role is likely mediated in part through the dense projections to the PVT from hypothalamic peptide transmitter systems such as orexin, and cocaine- and amphetamine-regulated transcript (CART, both of which play key roles in drug-seeking behaviour. Consistent with this proposition, we previously found that inactivation of the PVT or infusions of CART into the PVT suppressed drug-seeking behaviour in an animal model of contingent cocaine self-administration. Despite this work, very few studies have assessed the basic physiological properties of PVT neurons and how these parameters are altered by exposure to drugs such as cocaine. We set out to address these questions by employing an electrophysiological approach to record from anterior PVT (aPVT neurons from cocaine-treated and control animals. First, we determined the excitability of aPVT neurons by injecting a series of depolarizing current steps and characterizing the resulting action potential (AP discharge properties. Second, we investigated the effects of CART on excitatory synaptic inputs to aPVT neurons. We found that the majority of aPVT neurons exhibited tonic firing (TF, and initial bursting (IB consistent with previous studies. However, we also identified PVT neurons that exhibited delayed firing (DF, single spiking (SS and reluctant firing (RF. Interestingly, cocaine exposure shifted the proportion of aPVT neurons that exhibited TF. Further, application of CART suppressed excitatory synaptic drive to PVT. This finding is consistent with our previous behavioural data, which showed that CART signaling in the PVT negatively regulates drug-seeking behaviour. Together, these studies support previous anatomical evidence that the PVT can integrate reward-relevant information and provides a putative mechanism through which drugs of abuse can dysregulate this system in

  20. Characterization of seven cocaine- and amphetamine-regulated transcripts (CARTs) differentially expressed in the brain and peripheral tissues of Solea senegalensis (Kaup).

    Science.gov (United States)

    Bonacic, Kruno; Martínez, Almudena; Martín-Robles, Águeda J; Muñoz-Cueto, José A; Morais, Sofia

    2015-12-01

    CART (cocaine- and amphetamine-regulated transcript) is a peptide with neurotransmitter and neuroendocrine functions with several key roles, both centrally and peripherally. In mammals there is a single gene that produces two alternatively spliced variants in rat and a single transcript in human but in teleosts multiple genes have been found. In the present study we report the existence of seven transcripts in Senegalese sole and characterize their sequences and phylogenetic relationships, as well as their expression patterns in the brain and peripheral tissues, and in response to feeding. Both cart2a and cart4 showed a ubiquitous expression in the brain, while cart1a, cart1b and cart3a were similarly expressed and had higher transcript levels in the mesencephalon, followed by the diencephalon. On the other hand, cart2b showed a main expression in the olfactory bulbs, and cart3b was predominantly expressed in the spinal cord. The expression profile in peripheral tissues differed substantially between cart's, even between more recently duplicated genes. Collectively, all the tissues examined, except the muscle, express at least one of the different cart's, although the highest transcript levels were found in the brain, gonads (ovary and testis) and, in some cases, eye and kidney. Concerning the feeding response, only brain cart1a, cart2a and cart4 showed a significant postprandial regulation, although future studies are necessary to assess potential confounding effects of stress imposed by the force feeding technique employed. Senegalese sole exhibits the highest number of cart genes reported to date in a vertebrate species. Their differential expression patterns and feeding regulation suggest that multiple cart genes, resulting from at least 3 rounds of whole genome duplication, have been retained in fish genomes through subfunctionalization, or possibly even through neofunctionalization. PMID:26320854

  1. Quantitative Silylation Speciations of Primary Phenylalkyl Amines, Including Amphetamine and 3,4-Methylenedioxyamphetamine Prior to Their Analysis by GC/MS.

    Science.gov (United States)

    Molnár, Borbála; Fodor, Blanka; Boldizsár, Imre; Molnár-Perl, Ibolya

    2015-10-20

    A novel, quantitative trimethylsilylation approach derivatizing 11 primary phenylalkyl amines (PPAAs), including amphetamine (A) and 3,4-methylenedioxyamphetamine (MDA), was noted. Triggering the fully derivatized ditrimethylsilyl (diTMS) species with the N-methyl-N-(trimethylsilyl)-trifluoroacetamide (MSTFA) reagent, a new principle was recognized followed by GC/MS. In the course of method optimization, the complementary impact of solvents (acetonitrile, ACN; ethyl acetate, ETAC; pyridine, PYR) and catalysts (trimethylchlorosilane, TMCS; trimethyliodosilane, TMIS) was studied: the role of solvent and catalyst proved to be equally crucial. Optimum, proportional, huge responses were obtained with the MSTFA/PYR = 2/1-9/1 (v/v) reagent applying catalysts; A and MDA needed the TMIS, while the rest of PPAAs provided the diTMS products also with TMCS. Similar to derivatives generated with hexamethyldisilazane and perfluorocarboxylic acid (HMDS and PFCA) ( Molnár et al. Anal. Chem. 2015 , 87 , 848 - 852 ), the fully silylated PPAAs offer several advantages. Both of our methods save time and cost by allowing for direct injection of analytes into the column; this is in stark contrast with the requirement to evaporate acid anhydrides by nitrogen prior to their injection. Efficiences of the novel catalyzed trimethylsilylation (MSTFA) and our recently introduced (now, for A and MDA extended) acylation principle were contrasted. Catalyzed trimethylsilylation led to diTMS derivatives resulting in on average a 1.7 times larger response compared to the corresponding acylated species. Catalyzed trimethylsilylation of PPAAs, A, and MDA were characterized with retention, mass fragmentation, and analytical performance properties (R(2), LOQ values). The practical utility of ditrimethylsilyation was shown by analyzing A in urine and mescaline (MSC) in cactus samples. PMID:26412806

  2. 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. PMID:25455864

  3. Evidence for the participation of cocaine- and amphetamine-regulated transcript peptide (CART) in the fluoxetine-induced anti-hyperalgesia in neuropathic rats.

    Science.gov (United States)

    Upadhya, Manoj A; Dandekar, Manoj P; Kokare, Dadasaheb M; Singru, Praful S; Subhedar, Nishikant K

    2011-02-01

    Cocaine- and amphetamine-regulated transcript peptide (CART) has a role in chronic pain, and also in the actions of selective serotonin reuptake inhibitors (SSRIs) employed in the treatment of neuropathic pain. Herein, we test the hypothesis that CART may mediate the anti-hyperalgesic effect of the SSRI, fluoxetine, in neuropathic rats. Sciatic nerve in the right hind paw of rat was ligated to induce neuropathic pain, and the paw withdrawal latency was evaluated using Hargreaves apparatus. Fluoxetine [5-25mg/kg, intraperitoneal (ip)] or CART (54-102) [0.1-1.5μg/rat, intracerebroventricular (icv)] dose-dependently attenuated the hyperalgesic response observed in neuropathic rats, indicating anti-nociceptive properties of each agent. The anti-hyperalgesic effect of fluoxetine was potentiated by the subeffective dose of CART, and attenuated by CART-antibody (1:500 dilution; 5μl/rat, icv); CART-antibody had no effect per se. Isobolographic analysis showed a significant synergism between fluoxetine and CART, and antagonism between fluoxetine and CART-antibody. Immunocytochemical labeling with monoclonal antibodies against CART showed drastic increase in CART-immunoreactive fibers in the ventrolateral periaqueductal gray (VLPAG; 116%), dorsal subdivision of dorsal raphe nucleus (DRD; 176%), and locus coeruleus (LC; 733%) of neuropathic animals. Fluoxetine treatment significantly reduced the immunoreactivity in these areas. However, CART-immunoreactive cells and fibers in the arcuate nucleus did not respond to neuropathy or fluoxetine treatments. We suggest that the CART innervation of DRD, LC and VLPAG may be involved in the (i) central processing of neuropathic pain and (ii) fluoxetine-induced anti-hyperalgesic effect in neuropathic pain. PMID:21167239

  4. Amphetamine elevates phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the rat forebrain via activating dopamine D1 and D2 receptors.

    Science.gov (United States)

    Xue, Bing; Fitzgerald, Cole A; Jin, Dao-Zhong; Mao, Li-Min; Wang, John Q

    2016-09-01

    Psychostimulants have an impact on protein synthesis, although underlying molecular mechanisms are unclear. Eukaryotic initiation factor 2α-subunit (eIF2α) is a key player in initiation of protein translation and is regulated by phosphorylation. While this factor is sensitive to changing synaptic input and is critical for synaptic plasticity, its sensitivity to stimulants is poorly understood. Here we systematically characterized responses of eIF2α to a systemic administration of the stimulant amphetamine (AMPH) in dopamine responsive regions of adult rat brains. Intraperitoneal injection of AMPH at 5mg/kg increased eIF2α phosphorylation at serine 51 in the striatum. This increase was transient. In the medial prefrontal cortex (mPFC), AMPH induced a relatively delayed phosphorylation of the factor. Pretreatment with a dopamine D1 receptor antagonist SCH23390 blocked the AMPH-stimulated eIF2α phosphorylation in both the striatum and mPFC. Similarly, a dopamine D2 receptor antagonist eticlopride reduced the effect of AMPH in the two regions. Two antagonists alone did not alter basal eIF2α phosphorylation. AMPH and two antagonists did not change the amount of total eIF2α proteins in both regions. These results demonstrate the sensitivity of eIF2α to stimulant exposure. AMPH possesses the ability to stimulate eIF2α phosphorylation in striatal and mPFC neurons in vivo in a D1 and D2 receptor-dependent manner. PMID:27338925

  5. Repeated exposure to amphetamine during adolescence alters inhibitory tone in the medial prefrontal cortex following drug re-exposure in adulthood.

    Science.gov (United States)

    Paul, Kush; Kang, Shuo; Cox, Charles L; Gulley, Joshua M

    2016-08-01

    Behavioral sensitization following repeated amphetamine (AMPH) exposure is associated with changes in GABA function in the medial prefrontal cortex (mPFC). In rats exposed to AMPH during adolescence compared to adulthood, there are unique patterns of sensitization that may reflect age-dependent differences in drug effects on prefrontal GABAergic function. In the current study, we used a sensitizing regimen of repeated AMPH exposure in adolescent and adult rats to determine if a post-withdrawal AMPH challenge would alter inhibitory transmission in the mPFC in a manner that depends on age of exposure. Male Sprague-Dawley rats were treated with saline or 3mg/kg AMPH (i.p.) during adolescence [postnatal day (P) 27-P45] or adulthood (P85- P103) and were sacrificed either at similar ages in adulthood (∼P133; experiment 1) or after similar withdrawal times (3-4 weeks; experiment 2). Spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded in vitro from deep layer pyramidal cells in the mPFC using the whole-cell configuration. We found no effect of AMPH pre-exposure on baseline sIPSC frequency. Subsequent application of AMPH (25μM) produced a stable increase in sIPSC frequency in controls, suggesting that AMPH increases inhibitory tone in the mPFC. However, AMPH failed to increase sIPSCs in adolescent- or adult-exposed rats. In experiment 2, where withdrawal period was kept similar for both exposure groups, AMPH induced a suppression of sIPSC activity in adolescent-exposed rats. These results suggest that sensitizing treatment with AMPH during adolescence or adulthood dampens inhibitory influences on mPFC pyramidal cells, but potentially through different mechanisms. PMID:27085589

  6. Comparison of (+)-methamphetamine, ±-methylenedioxymethamphetamine, (+)-amphetamine and ±-fenfluramine in rats on egocentric learning in the Cincinnati water maze.

    Science.gov (United States)

    Vorhees, Charles V; He, Elizabeth; Skelton, Matthew R; Graham, Devon L; Schaefer, Tori L; Grace, Curtis E; Braun, Amanda A; Amos-Kroohs, Robyn; Williams, Michael T

    2011-05-01

    (+)-Methamphetamine (MA), (±)-3,4-methylenedioxymethamphetamine (MDMA), (+)-amphetamine (AMPH), and (±)-fenfluramine (FEN) are phenylethylamines with CNS effects. At higher doses, each induces protracted reductions in brain dopamine (DA) and/or serotonin. Chronic MA and MDMA users show persistent monoamine reductions and cognitive impairments. In rats, similar neurochemical effects can be induced, yet cognitive impairments have been difficult to demonstrate. We recently showed that rats treated on a single day with MA (10 mg/kg x 4 at 2 h intervals) exhibit impaired egocentric learning (Cincinnati water maze [CWM]) without affecting spatial learning (Morris water maze [MWM]) (Herring et al., [2008] Psychopharmacology (Berl) 199:637–650). Whether this effect is unique to MA or is a general characteristic of these drugs is unknown. Accordingly, this experiment compared these drugs on CWM performance. Drugs were given s.c. in four doses at 2 h intervals. MA doses were 10 or 12.5 mg/kg/dose, AMPH 25 mg/kg/dose (to match MA12.5-induced hyperthermia), MDMA 15 mg/kg/dose (previously established hyperthermia-inducing dose), and FEN 16.5 mg/kg/dose (equimolar to MA12.5). Two weeks later, rats were tested in the CWM (2 trials/day, 21 days). AMPH and MA (both doses) induced significant increases in CWM errors and latency to reach the goal with no differences in swim speed. MDMA and FEN did not significantly alter learning. Given that FEN selectively and MDMA preferentially affect serotonin whereas AMPH selectively and MA preferentially affect DA, the data suggest that egocentric learning may be predominantly dopaminergically mediated. PMID:20730798

  7. PREVALENCIA Y FACTORES ASOCIADOS AL CONSUMO DE ANFETAMINAS, EN ESTUDIANTES DEL PROGRAMA DE MEDICINA DE LA UNIVERSIDAD DE MANIZALES (COLOMBIA, 2010 The prevalence and factors associated with amphetamines use by medical students from the Universidad de Manizales (Colombia, 2010

    Directory of Open Access Journals (Sweden)

    Laura Barón

    2011-09-01

    Full Text Available Antecedentes. Un estudio previo realizado en la Universidad de Manizales midió el consumo de anfetaminas para mejorar rendimiento académico y demostró que el 42,3% de los estudiantes de Medicina consumían anfetaminas con este propósito. Objetivo. Confirmar este resultado e indagar por los factores asociados al consumo de anfetaminas, en estos estudiantes. Materiales y métodos. Se realizó un estudio de corte transversal en el que participaron estudiantes del Programa de Medicina de la Universidad de Manizales. La población fue de 615 mediante un muestreo probabilístico se seleccionaron 234 estudiantes. El instrumento utilizado fue una encuesta anónima que permitió identificar el consumo de estimulantes y factores de riesgo asociados. Resultados. El 51,9% (lc95%:44,9%-58,95 de la muestra aseveró haber consumido anfetaminas para mejorar rendimiento académico; de estos el 70,9% refirieron haber logrado el objetivo. No se encontró relación con factores de riesgo clásicos como ansiedad, depresión o funcionalidad familiar. El 87,9% no consumía estimulantes previo al ingreso al programa. Los semestres VI, VII, VIII y IX mostraron un mayor índice de consumo de: 73,3%, 60%, 68,8% y 57,7% respectivamente. Entre las razones de consumo se resaltan motivos académicos 32,5% y preservar estado de vigilia 18,7%. El 65,8% consumen bebidas alcohólicas. Conclusiones. El consumo de anfetaminas para mejorar rendimiento académico en los estudiantes del Programa de Medicina de la Universidad de Manizales es realmente alarmante. Se hace necesario intervenir en la causa y plantear soluciones para de esta manera, impactar los índices de consumo.Background. A prior study carried out in the Universidad de Manizales measured amphetamine consumption aimed at improving academic performance and revealed that 42.3% of medical students consumed amphetamines for such purpose. Objective. Confirming the aforementioned result and investigating the factors

  8. 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)

    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

  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

    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.

  10. Effect of amphetamine on extracellular concentrations of amino acids in striatum in neurotensin subtype 1 and 2 receptor null mice: a possible interaction between neurotensin receptors and amino acid systems for study of schizophrenia

    OpenAIRE

    Li, Zhimin; Liang, Yanqi; Boules, Mona; Gordillo, Andres; Richelson, Elliott

    2010-01-01

    Neurotensin (NT) is a tridecapeptide that acts as a neuromodulator in the central nervous system mainly through two NT receptors: NTS1 and NTS2. The present study was done to determine the roles of NTS1 and NTS2 on amino acid release in striatum with the use of NTS1 or NTS2 knock-out (-/-) mice given d-amphetamine. Both NTS1-/- and NTS2-/- mice had lower extracellular concentrations of D-serine in striatum than did wild type (WT) mice. NTS2-/- but not NTS1-/- mice also had significantly lower...

  11. 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. PMID:26780979

  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...... dependent kinase II- (CaMKII- ). A direct interaction between CaMKII- and DAT C-terminus was verified by the ability of C-terminal DAT GST fusion proteins to pull down both purified CaMKII- and CaMKII- from rat brain extracts. The ability of CaMKII- to exist in a complex with DAT was supported by co...

  13. 苯丙胺类兴奋剂所致精神障碍的临床诊治问题%Diagnosis and clinical management of amphetamine- induced psychosis

    Institute of Scientific and Technical Information of China (English)

    赵敏; 郝伟

    2011-01-01

    Psychosis induced by amphetamine-type stimulants (ATS) has become an important clinical challenge in psychiatric practice in China over recent years because of the rapid increase in the prevalence of ATS abuse. The authors introduce research on the genetic and pathological mechanisms underling ATS-induced psychosis and summarize findings on its clinical features, diagnosis and pharmacological treatment. They also discuss issues that need to be addressed in future research to increase understanding of ATS-induced psychosis and to improve the effectiveness of the clinical management of this condition.%近年国内苯丙胺类兴奋剂滥用日益严重,苯丙胺类兴奋剂所致精神障碍成为精神科临床的一个重要挑战.本文介绍了苯丙胺类兴奋剂所致精神障碍的分子遗传及病理机制方面的研究,并对其临床表现、诊断及药物治疗问题进行了综述,同时提出了未来研究的问题及方向.作者期望本文有助于深化读者对苯丙胺类兴奋剂所致精神障碍的了解及临床治疗疗效的提高.

  14. Influence of amphetamine-type stimulants on serum rapid plasma reagent titer in patients with syphilis%苯丙胺类兴奋剂对梅毒患者血RPR滴度的影响

    Institute of Scientific and Technical Information of China (English)

    李永喜; 张建明; 曲才杰; 毕健平; 李春霞

    2009-01-01

    目的 探讨苯丙胺类兴奋剂对梅毒患者血RPR滴度及阴转率的影响.方法 收集36例吸食苯丙胺类毒品的梅毒患者资料,取外周血检测RPR滴度、阴转率和免疫球蛋白水平,检测外周血单一核细胞产生IFN-γ、lL-4水平,并以44例梅毒患者和30例健康人作对照.结果 试验组RPR滴度明显低于对照组(P0.05),试验组IFN-γ水平低于对照组(P 0.05). The capability of PBMCs to product IFN-γ was highest in the stimulant-taking group, followed by the non-taking group and normal control group (all P < 0.05). No significant difference was observed in the capability of PBMCs to produce IL-4 between the stimulant-taking group and non-taking group, but a significant increment was noted in these patients compared with the normal human controls (all P < 0.01). Conclusion Amphetamine-type stimulants could reduce serum RPR titer and negative conversion rate of RPR in patients with syphilis, likely by impairing cellular immunity of patients.

  15. The harm of the abuse of amphetamine-type stimulants and its related interventional measures%苯丙胺类物质滥用危害及相关干预措施

    Institute of Scientific and Technical Information of China (English)

    杜江; 赵敏

    2014-01-01

    苯丙胺类物质以损害认知功能为主,使用者主要表现为幻觉、妄想、记忆力下降等精神症状和认知功能障碍,并且在上述精神症状影响下可能出现一系列的冲动、伤人及自伤行为。本文就苯丙胺类物质在我国的滥用趋势、作用机制、相关危害、治疗和干预措施进行介绍,以提高公众对其认识,降低苯丙胺类物质滥用对患者自身和社会的危害。%Amphetamine-type stimulants(AST)can damage the cognitive function of drug addicts who present mental symptoms as cognitive disfunction, delusions and hallucinations, which results in a series of impulse, wounding and self-injury behavior. This article introduces the epidemiological trend, the mechanism, the related hazard, the treatment and interventional measures of AST in our country in order to improve the awareness of AST in the publics and reduce AST harm to drug addicts and society.

  16. Current state and prospect of pharmacological approaches to amphetamine-type stimulants dependence%苯丙胺类依赖的药物治疗现状和展望

    Institute of Scientific and Technical Information of China (English)

    崔巍; 沈雯雯; 周文华; 韩怡凡

    2012-01-01

    笨丙胺类药物是国内第二大成瘾性药物,苯丙胺类依赖是一个重要的公共健康问题,但至今尚未发现有效的治疗药物.本文首先介绍了苯丙胺类依赖形成的多巴胺和非多巴胺机制,并对多巴胺转运体抑制剂、多巴胺受体部分激动剂及拮抗剂、谷氨酸受体拮抗剂、乙酰胆碱酯酶抑制剂、γ-氧基丁酸受体激动剂、5-羟色胺转运体抑制剂以及阿片受体拮抗剂等已用于苯丙胺类依赖治疗实践的药物进行了系统综述,并展望了苯丙胺类依赖治疗药物的研究方向.%Amphetamine-type stimulants ( ATS) are the second most widely used addictive drugs in China. ATS dependence has become a serious public heath problem. Currently, there is no pharmacological treatment with established efficacy for inhibiting this addictive disorder. Changes of non-dopaminergic systems implicated in ATS dependence, such as GABAergic, cholinergic and glutamatergic systems, suggest that this addictive disorder be treated with drugs targeting either the dopaminergic system or non-dopaminergic system. This paper reviews pharmacological candidates, including the inhibitors of dopamine and serotonin transporters, the partial agonists of do-pamine receptors, the antagonists of glutamate receptor, and the inhibitors of acetylcholinesterase, which might be useful in the treatment of ATS dependence based on preclinical data. The prospect of novel anti-ATS dependence drugs being developed is also discussed.

  17. 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

  18. Control study on clinical features of mental and behavior disorders as wel as schizophrenia caused by stimulant of amphetamines%苯丙胺类兴奋剂所致精神和行为障碍与精神分裂症临床特征对照研究

    Institute of Scientific and Technical Information of China (English)

    戴建磊

    2014-01-01

    Objective:To comparatively study the clinical features of mental and behavior disorders as wel as schizophrenia caused by stimulant of amphetamines.Methods:60 patients with mental and behavior disorders caused by stimulant of amphetamines in our hospital from Mar 2010 to Mar 2012 were selected as the amphetamine group,and selected another 60 schizophrenia patients as the schizophrenia group,clinicaL features of two groups were compared.Results:Differences of hal ucination,delusion of jealousy,delusion of grandeur,thought loose,excited and radical,insight between two groups were significant,with statistical significance(p<0.05).Efficiency of amphetamine group (98.33%) was significantly higher than schizophrenia group (66.67%),difference of two groups was statistical y significant (p<0.05).Conclusion:Clinical features of mental and behavior disorders as wel as schizophrenia caused by stimulant of amphetamines are similar,and differences of hal ucination,delusion of jealousy,delusion of grandeur,thought loose,excited and radical,insight between two groups are significant,clinical heal rate is higher,it needs to be further studyed in the future.%目的:对照研究苯丙胺类兴奋剂所致精神和行为障碍与精神分裂症临床特征。方法:选取60例2010年3月-2012年3月期间在我院接受治疗的苯丙胺类兴奋剂所致精神和行为障碍患者为苯丙胺组,选取同期的60例精神分裂症患者为精神分裂组,比较分析两组患者的临床特征。结果:苯丙胺组的60例患者与精神分裂组的60例患者在视幻觉、嫉妒妄想、夸大妄想、思维涣散、兴奋激进、无自知力等方面差异显著,均具有统计学意义(P<0.05)。苯丙胺组的治疗有效率为98.33%显著优于精神分裂组的治疗有效率为66.67%,两组差异显著具有统计学意义(P<0.05)。结论:苯丙胺类兴奋剂所致精神和行为障碍与精神分裂症临床特征相似,在视幻觉、嫉妒妄

  19. 苯丙胺模型大鼠海马差异表达微小核糖核酸的研究%Microaaray-based analysis of micro-ribonucleic acid expression in an animal model of amphetamine

    Institute of Scientific and Technical Information of China (English)

    荣晗; 刘铁榜; 杨海晨; 冯飞; 徐丹; 刘静静; 张建; 沈其杰

    2013-01-01

    Objective This study compared the difference of micro-ribonucleic acid (microRNA) expression in hippocampus of rat brain between an animal model of amphetamine(AMPH) and the normal by using the microRNA microaaray chip technology.Methods Twenty male SD rats were divided into control group(10) and AMPH group(10).The differential expression of microRNA was screened by using the microRNA microaaray chip technology.The microRNAs and target proteins expression in the hippocampus in AMPH model were verified by real time PCR and western blot.Results (1) Numbers of crossings (28.21 ±2.22)and rearings(82.33 ±4.61)were significantly increased in AMPH groups compared with the control groups (crossings 17.10 ± 1.94 and rearings 52.32 ± 3.76) (t =11.92,P < 0.01 ; t =15.95,P <0.01).(2) 136 microRNA were found in the hippocampus in AMPH group.Among those 14 raised up two times higher microRNAs and 6 lower two times microRNAs were found in the hippocampus in AMPH group.Three five times higher microRNAs were microRNA-134,microRNA-143 and microRNA-96,2 five times lower microRNAs were microRNA-132 and icroRNA-210.It was verified by real time PCR,the predicted target genes by miRanda algorithm of five times higher microRNAs were GRM-1,BDNF and SSTR-1.(3) The target genes were detected using Western blot,the relative contains of GRM-1 (0.18 ± 0.02),BDNF (0.21 ± 0.02) and SSTR-1 (0.42 ± 0.02) in AMPH group were significantly lower than control group (0.28 ±-0.03,0.31 ±0.03,0.59 ±0.03)(t =8.77,P<0.05; t =8.77,P<0.05; t =14.91,P<0.05).Conclusion This findings indicate that there be microRNAs expression difference in AMPH model hippocampus.%目的 初步探讨苯丙胺(amphetamine,AMPH)模型大鼠海马的微小核糖核酸(microRNA)的表达情况.方法 应用microRNA微阵列芯片技术筛选AMPH模型大鼠(AMPH模型组,10只)和对照大鼠(对照组,10只)海马差异表达microRNA;选取有明显表达变化的microRNA,采用实时定量聚合酶链反应

  20. Stimulant ADHD Medications -- Methylphenidate and Amphetamines

    Science.gov (United States)

    ... to improve ADHD symptoms along with the patient’s self-esteem, thinking ability, and social and family interactions. Do ... that stimulants prescribed to treat a child’s or adolescent’s ADHD could affect an individual’s vulnerability to developing ...

  1. 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. PMID:24135845

  2. Amphetamine Increases Errors During Episodic Memory Retrieval

    OpenAIRE

    Ballard, Michael Edward; Gallo, David A.; de Wit, Harriet

    2014-01-01

    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 wh...

  3. 78 FR 67365 - Determination That Adderall (Amphetamine Aspartate; Amphetamine Sulfate; Dextroamphetamine...

    Science.gov (United States)

    2013-11-12

    .../ Forest, IL 60045- milliliter (mL). 5046. NDA 018726 WESTCORT Ranbaxy Inc., 600 (hydrocortisone College Rd... acetate) Tablet; Pharmaceutical Oral, 50 mg, 100 Corp., 7720 North mg, 150 mg. Dobson Rd., Scottsdale,...

  4. 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

  5. 缅甸籍跨境女性性工作者苯丙胺类兴奋剂使用与高危性行为的相关性分析%Comparative analysis of the correlation between Amphetamine-type stimulants use and high-risk sexual behavior among Myanmar female sex workers

    Institute of Scientific and Technical Information of China (English)

    朱靖; 罗志; 杨佳; 朵林; 薛皓铭; 王蓓

    2016-01-01

    目的 探索缅甸籍跨境女性性工作者苯丙胺类兴奋剂(Amphetamine-Type Stimulant,ATS)使用与高危性行为之间的关系.方法 2013年3月至4月,在云南省德宏州瑞丽市姐告和缅甸木姐口岸,采用雪球抽样方式纳入147名调查对象.自行设计问卷进行横断面调查,内容包括人口学特征、ATS使用情况、性行为特征等.同时,对调查对象进行HIV血检和甲基安非他明尿检.结果 甲基安非他明尿检阳性者46人,使用的ATS主要为冰毒和摇头丸.23人(50.00%)曾在服用ATS后与客人发生性行为且没有坚持使用安全套.ATS尿检阳性(OR=3.362,95%CI:1.625 ~6.956)和ATS药效期间与客人发生性行为(OR=1.911,95%CI:1.007~3.625)是促进缅甸籍跨境女性性工作者发生高危性行为的危险因素.结论 针对缅甸籍跨境女性性工作者ATS使用的相关干预措施应当成为今后中缅边境地区该人群行为干预工作的重点,同时,应当继续加强安全套使用的宣传教育和行为干预工作.

  6. Amphetamine Self-Administration Attenuates Dopamine D2 Autoreceptor Function

    OpenAIRE

    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...

  7. 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...

  8. Schizophrenia, amphetamine-induced sensitized state and acute amphetamine exposure all show a common alteration: increased dopamine D2 receptor dimerization

    OpenAIRE

    Wang Min; Pei Lin; Fletcher Paul J; Kapur Shitij; Seeman Philip; Liu Fang

    2010-01-01

    Abstract Background All antipsychotics work via dopamine D2 receptors (D2Rs), suggesting a critical role for D2Rs in psychosis; however, there is little evidence for a change in receptor number or pharmacological nature of D2Rs. Recent data suggest that D2Rs form dimers in-vitro and in-vivo, and we hypothesized that schizophrenia, as well as preclinical models of schizophrenia, would demonstrate altered dimerization of D2Rs, even though the overall number of D2Rs was unaltered. Methods We mea...

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

    DEFF Research Database (Denmark)

    Binda, Francesca; Dipace, Concetta; Bowton, Erica; Robertson, Sabrina D; Lute, Brandon J; Fog, Jacob U; Zhang, Minjia; Sen, Namita; Colbran, Roger J; Gnegy, Margaret E; Gether, Ulrik; Javitch, Jonathan A; Erreger, Kevin; Galli, Aurelio

    2008-01-01

    The soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein syntaxin 1A (SYN1A) interacts with and regulates the function of transmembrane proteins, including ion channels and neurotransmitter transporters. Here, we define the first 33 amino acids of the N terminus of the do...

  10. BUPROPION, D-AMPHETAMINE, AND AMITRIPTYLINE-INDUCED CONDITIONED TASTE AVERSION IN RATS: DOSE EFFECTS

    Science.gov (United States)

    Nine groups of rats (n+6 per group) were adapted to a daily one-half hour period of water availability. When intake had stabilized, they were allowed access to a 0.1% (w/v) solution of saccharin, and immediately afterward were given IP injections of isotonic saline; bupropion HCl...

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

    NARCIS (Netherlands)

    Achterberg, E.J.M.; Trezza, V.; Siviy, S.M.; Schrama, L.H.; Schoffelmeer, A.N.; Vanderschuren, L.J.M.J.

    2014-01-01

    Rationale 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 involv

  12. Effects of acute amphetamine (AMPH) treatment on rat striatal dopamine (DA) receptor activity

    International Nuclear Information System (INIS)

    Upon administration of AMPH rats display a complex series of dose and time dependent behaviors and changes in dopaminergic activity. They found a decrease in D1 DA receptor-stimulated adenylate cyclase (DA-AC) activity in rat striatal membranes after acute in vivo AMPH at a dose and time of intense stereotyped behavior. The Ka for D1-AC activity increased and the Vmax decreased in striatal membranes from rats given 7.5 mg/kg AMPH i.p. and killed 1 hr later as compared to saline (SAL) controls. They examined whether the decrease of DA-AC was due to a change in receptor number or activation of GTP-binding protein, Ns. Female Holtzman rats were injected with SAL or 7.5 mg/kg AMPH and killed 1 hr later. A 27,000 x g striatal particulate fraction was prepared for AC assay or [3H]DA binding with 10 nM spiroperidol. They found no difference in stimulation of AC by NaF, GTP or GppNHp at any dose tested in membranes from SAL- and AMPH-treated rats. Calmodulin-stimulated AC was also unchanged after AMPH. Specific binding at a saturating concentration of [3H]DA was 191 +/- 31 and 117 +/- 14 fmol/mg prot in membranes from SAL- and AMPH-treated rats, respectively. This suggests an alteration is occurring at the level of the D1 receptor rather than at coupling of Ns with the AC catalytic subunit

  13. Spect with 123 I-amphetamine as a diagnostic aid for neurogical diseases

    International Nuclear Information System (INIS)

    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)

  14. Heroin and amphetamine users display opposite relationships between trait and neurobehavioral dimensions of impulsivity

    OpenAIRE

    Vassileva, Jasmin; Paxton, Jessica; Moeller, F. Gerard; Wilson, Michael; Bozgunov, Kiril; Martin, Eileen; Gonzalez, Raul; Vasilev, Georgi

    2013-01-01

    The multidimensional construct of impulsivity is implicated in all phases of the addiction cycle. Substance dependent individuals (SDIs) demonstrate elevated impulsivity on both trait and laboratory tests of neurobehavioral impulsivity; however our understanding of the relationship between these different aspects of impulsivity in users of different classes of drugs remains rudimentary. The goal of this study was to assess for commonalities and differences in the relationships between trait a...

  15. Pheochromocytoma cell PC12 contain binding sites for cart (cocaine- and amphetamine-regulated transcript)

    Czech Academy of Sciences Publication Activity Database

    Maixnerová, Jana; Blokešová, Darja; Matyšková, Resha; Haugvicová, Renata; Šloncová, Eva; Elbert, Tomáš; Železná, Blanka; Maletínská, Lenka

    Praha: Ústav organické chemie a biochemie AV ČR, 2007 - (Slaninová, J.), s. 72-74. (Collection Symposium Series. 9). ISBN 978-80-86241-28-9. [Biologically Active Peptides /10./. Praha (CZ), 11.04.2007-13.04.2007] Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510; CEZ:AV0Z50520514 Keywords : CART peptides * biological activity * specific binding Subject RIV: CE - Biochemistry

  16. 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

  17. 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

  18. Pheochromocytoma cell PC12 contain binding sites for cart (cocaine- and amphetamine-regulated transcript)

    Czech Academy of Sciences Publication Activity Database

    Maixnerová, Jana; Blokešová, Darja; Matyšková, Resha; Haugvicová, Renata; Šloncová, Eva; Elbert, Tomáš; Železná, Blanka; Maletínská, Lenka

    Praha: Ústav organické chemie a biochemie AV ČR, 2007. s. 43. ISBN 978-80-86241-00-5. [Biologically Active Peptides /10./. 11.04.2007-13.04.2007, Praha] Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514 Keywords : CART peptides * biological activity * specific binding Subject RIV: CC - Organic Chemistry

  19. 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

  20. 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

  1. 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 response

  2. History of Childhood Adversity is Positively Associated with Ventral Striatal Dopamine Responses to Amphetamine

    OpenAIRE

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

    2014-01-01

    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 deg...

  3. 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…

  4. Amphetamine alters Ras-guanine nucleotide-releasing factor expression in the rat striatum in vivo

    OpenAIRE

    Parelkar, Nikhil K.; Jiang, Qian; Chu, Xiang-Ping; Guo, Ming-Lei; Mao, Li-Min; WANG, John Q.

    2009-01-01

    Ras-guanine nucleotide-releasing factors (Ras-GRFs) are densely expressed in neurons of the mammalian brain. As a Ras-specific activator predominantly concentrated at synaptic sites, Ras-GRFs activate the Ras-mitogen-activated protein kinase (Ras-MAPK) cascade in response to changing synaptic inputs, thereby modifying a variety of cellular and synaptic activities. While the Ras-MAPK cascade in the limbic reward circuit is well-known to be sensitive to dopamine inputs, the sensitivity of its u...

  5. "Natural Amphetamine" Khat: A Cultural Tradition or a Drug of Abuse?

    Science.gov (United States)

    Patel, Nilesh B

    2015-01-01

    Khat, Catha edulis Forsk, is among the most widely used plant-based psychoactive substance in the world. Grown in Eastern Africa, Horn of Africa, and southwestern part of the Arabian Peninsula, its fresh young leaves and twigs are used daily by over 20 million people for the psychostimulatory effects it produces in the user, a practice deeply rooted in the history, tradition, and culture of the indigenous population. Once hardly known outside the regions where it is grown and used, khat use has now spread to other countries. This review will cover the, phytochemistry, pharmacokinetics of the active ingredients-cathinone, cathine, norephedrine, neurochemistry, effects on cognitive and executive functions as well as its ability to produce dependency in the user. Whether it is an innocuous cultural practice or a drug of abuse is debatable as the preclinical and clinical data needed to arrive at an authoritative conclusion is lacking. PMID:26070760

  6. 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 ...

  7. Effects of Acute Amphetamine Exposure on Two Kinds of Pavlovian Approach Behavior

    OpenAIRE

    Holden, John Michael; Peoples, Laura L.

    2009-01-01

    Two kinds of Pavlovian conditioned approach behavior are possible: approach of the CS (sign-tracking) and approach of the US (goal-tracking). We hypothesized that administration of AMP would increase sign-tracking and decrease goal-tracking. However, increasing doses of AMP (up to 2.0 mg/kg) decreased measures of sign-tracking while simultaneously increasing measures of goal-tracking. Administration of AMP may shift responding from cues distant from the CS to cues closer to the CS.

  8. Protective effect of pentoxifylline on male Wistar rat testicular germ cell apoptosis induced by 3,4-methylenedioxymeth amphetamine

    OpenAIRE

    Mahnaz Nouri; Shabnam Movassaghi; Alireza foroumadi; Mansooreh Soleimani; Zahra Nadia Sharifi

    2016-01-01

    Objective(s): 3, 4-methylenedioxymethamphetamine (MDMA) one of the methamphetamine derivatives that affect the reproductive system, has not been well understood. Many young people are consumers of drugs such as MDMA that can affect their reproductive capability. Apoptosis is the main mechanism for male infertility. Pentoxifylline (PTX) increases cAMP intracellularly and reduces tumor necrosis factor-α. This study aimed to investigate the protective effect of PTX administration in MDMA-indu...

  9. Effects of dexamphetamine-induced dopamine release on resting-state network connectivity in recreational amphetamine users and healthy controls.

    Science.gov (United States)

    Schrantee, Anouk; Ferguson, Bart; Stoffers, Diederick; Booij, Jan; Rombouts, Serge; Reneman, Liesbeth

    2016-06-01

    Dexamphetamine (dAMPH) is not only used for the treatment of attention deficit hyperactivity disorder (ADHD), but also as a recreational drug. Acutely, dAMPH induces release of predominantly dopamine (DA) in the striatum, and in the cortex both DA and noradrenaline. Recent animal studies have shown that chronic dAMPH administration can induce changes in the DA system following long-term exposure, as evidenced by reductions in DA transporters, D2/3 receptors and endogenous DA levels. However, only a limited number of studies have investigated the effects of dAMPH in the human brain. We used a combination of resting-state functional magnetic resonance imaging (rs-fMRI) and [(123)I]IBZM single-photon emission computed tomography (SPECT) (to assess baseline D2/3 receptor binding and DA release) in 15 recreational AMPH users and 20 matched healthy controls to investigate the short-, and long-term effects of AMPH before and after an acute intravenous challenge with dAMPH. We found that acute dAMPH administration reduced functional connectivity in the cortico-striatal-thalamic network. dAMPH-induced DA release, but not DA D2/3 receptor binding, was positively associated with connectivity changes in this network. In addition, acute dAMPH reduced connectivity in default mode networks and salience-executive-networks networks in both groups. In contrast to our hypothesis, no significant group differences were found in any of the rs-fMRI networks investigated, possibly due to lack of sensitivity or compensatory mechanisms. Our findings thus support the use of ICA-based resting-state functional connectivity as a tool to investigate acute, but not chronic, alterations induced by dAMPH on dopaminergic processing in the striatum. PMID:26149196

  10. Effects of dexamphetamine-induced dopamine release on resting-state network connectivity in recreational amphetamine users and healthy controls.

    NARCIS (Netherlands)

    Schrantee, A.; Ferguson, B.; Stoffers, D.; Booij, J.; Rombouts, S.A.; Reneman, L.

    2016-01-01

    Dexamphetamine (dAMPH) is not only used for the treatment of attention deficit hyperactivity disorder (ADHD), but also as a recreational drug. Acutely, dAMPH induces release of predominantly dopamine (DA) in the striatum, and in the cortex both DA and noradrenaline. Recent animal studies have shown

  11. The use of amphetamine type stimulants and the normalization of recreational drug use among people who attend electronic music events

    OpenAIRE

    Sande, Matej

    2008-01-01

    The article presents the results and findings of a quantitative and qualitative research into the use of ATS and the characteristics of attending electronic music events in Slovenia. The main conclusions of the study that concern the prevalence of drug use at electronic music events point to a decrease in the prevalence of ecstasy use and an increase in the use of cocaine and methamphetamine. The analysis of the interviews in the qualitative part reflects the influence...

  12. Protective effect of pentoxifylline on male Wistar rat testicular germ cell apoptosis induced by 3,4-methylenedioxymeth amphetamine

    Science.gov (United States)

    Nouri, Mahnaz; Movassaghi, Shabnam; foroumadi, Alireza; Soleimani, Mansooreh; Sharifi, Zahra Nadia

    2016-01-01

    Objective(s): 3, 4-methylenedioxymethamphetamine (MDMA) one of the methamphetamine derivatives that affect the reproductive system, has not been well understood. Many young people are consumers of drugs such as MDMA that can affect their reproductive capability. Apoptosis is the main mechanism for male infertility. Pentoxifylline (PTX) increases cAMP intracellularly and reduces tumor necrosis factor-α. This study aimed to investigate the protective effect of PTX administration in MDMA-induced apoptosis in testes of male Wistar rats. Materials and Methods: Thirty male Wistar rats weighing 250–300 g were randomly divided into five groups: control group (without any intervention), group receiving 7.5 mg/kg MDMA three times every two hours for one day, first experimental group receiving 100 mg/kg PTX just at the time of third injection of MDMA, second experimental group receiving 100 mg/kg PTX a week before MDMA administration, and the vehicle group, which received MDMA+saline. Two weeks later, testes were removed and prepared for H&E staining, TUNEL and Western blot techniques. Results: There was a significant decrease of the score in the MDMA group compared with the control group. In first and second experimental groups, the quality of seminiferous epithelium was improved compared with the MDMA group. The number of TUNEL-positive cells/tubule increased in MDMA and vehicle groups, which is decreased by administration of PTX before MDMA. Expression of active caspase-3 significantly increased in MDMA group, which is significantly decreased by administration of PTX before MDMA. Conclusion: PTX can significantly reduce the severity of lesions in the testes following administration of MDMA. PMID:27482346

  13. 75 FR 69088 - Determination That Amphetamine Sulfate, 5 and 10 Milligram Tablets, Was Not Withdrawn From Sale...

    Science.gov (United States)

    2010-11-10

    ... Tablets, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug... listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162). Under Sec... from sale for reasons of safety or effectiveness before an ANDA that refers to that listed drug may...

  14. 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

  15. Synergistic effect of CART (cocaine and amphetamine regulated transcript) peptide and cholecystokinin in lean and diet-induced obese mice

    Czech Academy of Sciences Publication Activity Database

    Maixnerová, Jana; Matyšková, Resha; Blokešová, Darja; Haugvicová, Renata; Železná, Blanka; Maletínská, Lenka

    Paris: -, 2007. [World Congress on Prevention and Therapies against Obesity /2./. 14.06.2007-15.06.2007, Paris] Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510 Keywords : cocaine * cholecystokinin * synergy Subject RIV: CE - Biochemistry

  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. 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; Matyšková, Resha; Haugvicová, Renata; Slaninová, Jiřina; Železná, Blanka

    Geneva: Kenes International, 2007 - (Rolka, K.; Rekowski, P.; Silberring, J.), s. 254-255 ISBN 978-965-555-297-3. [European Peptide Symposium /29./. Gdansk (PL), 03.09.2006-08.09.2006] R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510; CEZ:AV0Z50520514 Keywords : peptides * CART Subject RIV: CC - Organic Chemistry

  18. 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

  19. EFFECTS OF THE FUNGICIDE TRIADMEFON ON FIXED-INTERVAL PERFORMANCE: COMPARISON WITH METHYLPHENIDATE, D-AMPHETAMINE AND CHLORPROMAZINE

    Science.gov (United States)

    Triadimefon is a fungicide that has recently been shown to increase motor activity and also to increase rates of schedule-controlled responding. hese findings indicate that triadimefon resembles psychomotor stimulants. he present experiment was designed to compare triadimefon to ...

  20. 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

    INTRODUCTION: Muscarinic M(5) receptors are the only muscarinic receptor subtype expressed by dopamine-containing neurons of the ventral tegmental area. These cells play an important role for the reinforcing properties of psychostimulants and M(5) receptors modulate their activity. Previous studi...

  1. A scoping review of home-produced heroin and amphetamine-type stimulant substitutes: implications for prevention, treatment, and policy

    OpenAIRE

    Hearne, Evelyn; Grund, Jean-Paul Cornelius; Van Hout, Marie Claire; McVeigh, Jim

    2016-01-01

    Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and i...

  2. Amphetamine Fails to Alter Cued Recollection of Emotional Images: Study of Encoding, Retrieval, and State-Dependency

    OpenAIRE

    Weafer, Jessica; Gallo, David A.; de Wit, Harriet

    2014-01-01

    Stimulant drugs facilitate both encoding and retrieval of salient information in laboratory animals, but less is known about their effects on memory for emotionally salient visual images in humans. The current study investigated dextroamphetamine (AMP) effects on memory for emotional pictures in healthy humans, by administering the drug only at encoding, only at retrieval, or at both encoding and retrieval. During the encoding session, all participants viewed standardized positive, neutral, a...

  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. An Association Study of the Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Amphetamine Response

    OpenAIRE

    Brody A Flanagin; Cook, Edwin H.; de Wit, Harriet

    2006-01-01

    Although genetic factors are known to be important in addiction, no candidate genes have yet been consistently linked to drug use or abuse. Brain-derived neurotrophic factor (BDNF), which has been implicated in the behavioral response to psychomotor stimulants and potentiates neurotransmitters that are strongly linked to addiction, is a logical candidate gene to study. Using a drug challenge approach, we tested for association between BDNF G196A (val66met) genotype and subjective responses to...

  5. 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.

  6. 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; Cumming, Paul

    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...

  7. 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)

    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

  8. Injection of Cocaine-Amphetamine Regulated Transcript (CART) peptide into the nucleus accumbens does not inhibit caffeine-induced locomotor activity: Implications for CART peptide mechanism.

    Science.gov (United States)

    Job, Martin O

    2016-09-01

    Much evidence suggests that intra-nucleus accumbens (NAc) CART peptide (CART 55-102) injection inhibits locomotor activity (LMA) when there is an increase in the release and activity of dopamine (DA) in the NAc. However, this hypothesis has not been fully tested. One way to examine this is to determine if there is a lack of effect of intra-NAc CART peptide on LMA that does not involve increases in DA release in the NAc. Several studies have suggested that caffeine-induced LMA does not involve extracellular DA release in the NAc core. Therefore, in this study, we have examined the effect of injections of CART peptide (2.5μg) into the NAc core on the locomotor effects of caffeine in male Sprague-Dawley rats. Several LMA relevant doses of caffeine were used (0, 10, 20mg/kg i.p.), and an inverted U response curve was found as expected. We determined, in the same animals, that intra-NAc CART peptide had no effect on caffeine-induced LMA whereas it blunted cocaine-mediated LMA, as shown by other reports. We also extended a previous observation in mice by showing that at a LMA activating dose of caffeine there is no alteration of CART peptide levels in the NAc of rats. Our study supports the hypothesis that the inhibitory effects of CART peptide in the NAc may be exerted only under conditions of increased extracellular DA release and activity in this region. Our results also suggest that intra-NAc CART 55-102 does not generally inhibit increases in LMA due to all drugs, but has a more specific inhibitory effect on dopaminergic neurotransmission. PMID:27168116

  9. 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

  10. Alleviation of x-irradiation-based deficit in memory-based learning by d-amphetamine: Suggestions for attention deficit–hyperactivity disorder

    OpenAIRE

    Highfield, D. A.; Hu, D.; Amsel, A

    1998-01-01

    Selective exposure to x-irradiation during infancy, from postnatal days (PND) 2–11 in the rat, results in severe hippocampal granule cell hypoplasia. Preweanling (PND 17–18) rats, which suffer such hippocampal granule-cell agenesis, show deficits in patterned single alternation (PSA), a form of memory-based learning. Deficits in short-term memory along with increased arousal have been suggested as characteristic of children diagnosed with attention deficit–hyperactivity disorder (ADHD). We re...

  11. 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

  12. Cocaine- and Amphetamine-Regulated Transcript (CART) Messenger RNA Expression is Regulated by Food Intake in the Brain of the Channel Catfish (Ictalurus punctatus)

    Science.gov (United States)

    Increased growth is included as a selection criterion at the USDA Catfish Genetics Research Unit, Stoneville, MS, USA. Faster growth of selected channel catfish is typically attributed to their ability to consume more feed. While endocrine and neural factors and mechanisms that regulate feed intak...

  13. Iodination of CART (61-102) (cocaine- and amphetamine-regulated transcript) peptide, separation and characterization of products and evaluation of their biological activity

    Czech Academy of Sciences Publication Activity Database

    Elbert, Tomáš; Maletínská, Lenka; Maixnerová, Jana; Železná, Blanka

    Bad Soden: International Isotope Society, 2007. s. 39. [WorkshopThe Synthesis and Applications of Isotopes and Isotopically Labelled Compounds /14./. 21.06.2007-22.06.2007, Bad Soden] Institutional research plan: CEZ:AV0Z40550506 Keywords : CART(61-102) * 125l-labeled peptide Subject RIV: CC - Organic Chemistry

  14. 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)

    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.)

  15. Attracting states in anterior cingulate cortex populations associated with decision making: Altered dynamics when targeting dopamine system with d-Amphetamine

    OpenAIRE

    Emili Balaguer-Ballester; Lapish, Christopher C; Seamans, Jeremy K.

    2011-01-01

    A frequent hypothesis in theoretical neuroscience is that cognitive entities are represented and processed by attracting states of the underlying neural system (Balaguer et al., 2011; Durstewitz et al., 2000). For instance, different attractor-like states may represent different spatial locations or cognitive entities, and transitions between these attracting sets could be associated with the recall of a memory sequence or the execution of a motor plan. Attractor states underlying cognition w...

  16. 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 ostatní: GA ČR(CZ) GA305/06/0427 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

  17. Prenatal immune challenge in rats: Effects of polyinosinic-polycytidylic acid on spatial learning, prepulse inhibition, conditioned fear, and responses to MK-801 and amphetamine

    OpenAIRE

    Vorhees, Charles V.; Graham, Devon L.; Braun, Amanda A.; Schaefer, Tori L.; Skelton, Matthew R.; Richtand, Neil M; Williams, Michael T.

    2014-01-01

    Prenatal maternal immune activation increases risk for schizophrenia and/or autism. Previous data suggest that maternal weight change in response to the immune activator polyinosinic-polycytidylic (Poly IC) in rats influences the severity of effect in the offspring as does the exposure period. We treated gravid Sprague-Dawley rats from E14-18 with 8 mg/kg/day Poly IC or saline. The Poly IC group was divided into those that gained the least weight or lost (Poly IC (L)) and those that gained th...

  18. Examination of methylphenidate-mediated behavior regulation by glycogen synthase kinase-3 in mice

    OpenAIRE

    Mines, Marjelo A.; Beurel, Eleonore; Jope, Richard S

    2012-01-01

    Abnormalities in dopaminergic activity have been implicated in psychiatric diseases, such as attention deficit hyperactivity disorder (ADHD), and are treated with therapeutic stimulants, commonly methylphenidate or amphetamine. Amphetamine administration increases glycogen synthase kinase-3 (GSK3) activation, which is necessary for certain acute behavioral responses to amphetamine, including increased locomotor activity and impaired sensorimotor gating. Here, we tested if modulating GSK3 by a...

  19. 微波萃取-气相色谱法测定尿液中的苯丙胺类毒品%Determination of amphetamines in human urine using microwave extraction-gas chromatography

    Institute of Scientific and Technical Information of China (English)

    王继芬; 孙洪峰; 叶能胜; 谷学新; 李文君; 李瑛

    2008-01-01

    建立了人体尿液中甲基苯丙胺(MA)、3,4-亚甲二氧基苯丙胺(MDA)、3,4-亚甲二氧基甲基苯丙胺(MDMA)的微波萃取-气相色谱(GC)测定方法.分别考察了萃取溶剂种类、用量、pH值以及萃取温度、时间等因素对萃取率的影响.实验结果表明,尿液中MA,MDA,MDMA的最佳提取条件为:调节尿样pH为12,以环己烷为萃取溶剂,于40℃下微波提取10 min.在此条件下MA,MDA,MDMA的平均回收率分别为92.25%,85.94%和91.50%,相对标准偏差分别为5.5%,5.5%和6.1%(n=5),提取液经气相色谱-氢火焰离子化检测器(GC-FID)检测,3种药物与基体得到了很好的分离,对尿液中MA,MDA,MDMA的最低检测限分别为10,20和20 ng/mL.该方法未对药物进行衍生化,是一种快速、准确、灵敏度高的同时测定尿液中MA,MDA,MDMA的方法.

  20. INTERACTIONS OF MK-801 WITH THE AMPHETAMINE ANALOGUES D-METHAMPHETAMINE (D-METH),3,4,-METHYLENEDIOXYMETHAMPHETAMINE (D-MDMA) OR D-FENFLURAMINE (D-FEN): NEURAL DAMAGE AND NEURAL PROTECTION

    Science.gov (United States)

    Glutaminergic mechanisms have been implicated in a variety of forms of brain trauma and injury as well as the CNS alterations observed in Alzheimer's and Huntington's diseases. An over activation of excitatory amino acid (EEA) receptors is postulated to play a key role in the ind...

  1. BDNF Overexpression in the Ventral Tegmental Area Prolongs Social Defeat Stress-induced Cross-Sensitization to Amphetamine and Increases ΔFosB Expression in Mesocorticolimbic Regions of Rats

    OpenAIRE

    Wang, Junshi; Fanous, Sanya; Terwilliger, Ernest F.; Bass, Caroline E.; Hammer, Ronald P; Nikulina, Ella M.

    2013-01-01

    Social defeat stress induces persistent cross-sensitization to psychostimulants, but the molecular mechanisms underlying the development of cross-sensitization remain unclear. One candidate is brain-derived neurotrophic factor (BDNF). The present research examined whether ventral tegmental area (VTA) BDNF overexpression would prolong the time course of cross-sensitization after a single social defeat stress, which normally produces transient cross-sensitization lasting

  2. 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

  3. Pentadecapeptide BPC 157 attenuates chronic amphetamineinduced behavior disturbances%十五肽BPC 157减弱慢性苯丙胺诱导的行为障碍

    Institute of Scientific and Technical Information of China (English)

    Predrag SIKIRIC; Gorana ARALICA; Gojko BULJAT; Ingrid PRKACIN; Martina LOVRIC-BENCIC; Jadranka SEPAROVIC; Sven SEIWERTH; Rudolf RUCMAN; Marijan PETEK; Branko TURKOVIC; Tihomil ZIGER; Nikola JELOVAC; Alenka BOBAN-BLAGAIC; Vlado BEDEKOVIC; Ante TONKIC; Slaven BABIC; Andjelka JELOVAC-GJELDUM; Goran DODIG; Mario STARESINIC; Tomislav ANIC; Ivan ZORICIC; Davor RAK; Darko PEROVIC

    2002-01-01

    AIM: To investigate the effect of pentadecapeptide BPC 157 on chronic exposure to amphetamine in rats,particularly the changes commonly referred in chronic amphetamine studies as tolerance (lesser grade of stereotyped behavior, without increased excitability) and reverse tolerance (ie, prominent stereotyped behavior and heightened startle response upon late amphetamine challenges ). METHODS: After initial application (initial single dose-regimen), amphetamine (10 mg/kg,ip) was given once daily till d 5 (continuous administration-regimen ), and thereafter on d 8, 16, and 46(intermittent administration regimen). For stereotyped behavior and heightened startle response the observation period was 120 min after amphetamine application, and each animal was observed for 10 s in 5 min intervals.Pentadecapeptide BPC 157 (10 μg/kg or 10 ng/kg, ip)or saline (5.0 mL/kg, ip) were given only at the beginning of the experiment, simultaneously with the initial dose of amphetamine. RESULTS: In relation to applied initial-single/continuous/intermittent amphetamine applications regimen, the control amphetamine rats throughout the experiment showed the changes in stereotyped behavior and heightened startle response,increment or decrement, commonly explained in chronic amphetamine studies as tolerance and reverse tolerance.After the initial application of the amphetamine, the higher BPC 157 dosage apparently attenuated the stereotyped behavior, while the lower dosage of BPC 157 did not reach a statistical significance. Considering the forthcoming amphetamine challenges, in the rats initially treated with pentadecapeptide BPC 157, either 10 μg- or 10 ng-dose, at the time of the first application of amphetamine, the stereotyped behavior remains to be attenuated after all additional amphetamine challenges (on d 2- 5, 8, 16, and 46). This attenuation was not limited to stereotyped behavior only. After the initial application of the amphetamine the heightened startle response was also

  4. Drugs and Young People

    Science.gov (United States)

    ... susceptible to drug abuse and addiction than adult brains. Abused drugs include Amphetamines Anabolic steroids Club drugs Cocaine Heroin Inhalants Marijuana Prescription drugs There are different ...

  5. 76 FR 5829 - Manufacturer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-02-02

    ... controlled substances: Drug Schedule Marihuana (7360) I Tetrahydrocannabinols (7370) I Amphetamine (1100) II... distribution to its customers. In reference to drug code 7360 (Marihuana), the company plans to...

  6. 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 amp

  7. 薄层色谱扫描法检测血浆中苯丙胺与3,4-亚甲基二氧基甲基苯丙胺%Identification of amphetamine and 3, 4-methylenedioxymethamphetamine (MDMA) in plasma by TLC scanning

    Institute of Scientific and Technical Information of China (English)

    陈朝阳; 王玉瑾

    2003-01-01

    目的建立血浆中苯丙胺(AM)、3,4-亚甲基二氧基甲基苯丙胺(MDMA)的薄层色谱扫描(TLCS)定性定量检测方法.方法样品经碱化,分别用乙酸乙酯与环己烷提取,薄层层析分离,薄层扫描定性和定量检测.结果AM、MDMA扫描线性范围均为0.2~15μg/斑点,提取回收率分别为(76.6±3.1)%和(78.4±4.7)%,最低检出限为0.2μg/斑点(S/N≥3).结论本方法可用于AM及MDMA中毒的快速检验.

  8. Rapid simultaneous determination of amphetamine,methamphetamine MDA and MDMA in urine using HS/SPME and GC/MS%顶空固相微萃取与气质联用快速检测尿液中苯丙胺、甲基苯丙胺、MDA和MDMA

    Institute of Scientific and Technical Information of China (English)

    李宏森; 黄克建; 林翠梧; 蒙念; 潘智文

    2007-01-01

    利用顶空固相微萃取(HS/SPME)结合气/质联用(GC/MS-SIM)技术同时快速检测尿液中苯丙胺、甲基苯丙胺、MDA和MDMA.80℃下采用100 μm聚二甲基硅氧烷萃取头萃取10 min,3-苯基-1-丙胺作内标,探讨了影响SPME萃取效果的萃取时间、盐浓度、酸碱条件等因素,优化了实验条件.结果:苯丙胺、甲基苯丙胺、MDA和MDMA在50~2000 ng/mL质量浓度范围内线性良好,相关系数(r2)分别为0.9985,0.9971,0.9928和0.9994,检测限(信噪比=3)0.09 ng/mL,0.02 ng/mL,1.71 ng/mL和0.15 ng/mL,定量限(信噪比=10)0.31 ng/mL,0.05 ng/mL,5.68 ng/mL,0.49 ng/mL.1 mL空白尿液加标250 ng和1 000 ng,回收率在82%~108%之间,相对标准偏差(RSD)<13%(n=5).建立的方法适用于尿液中苯丙胺、甲基苯丙胺、MDA和MDMA的同时快速检测.

  9. Determination of amphetamine, methamphetamine, MDA and MDMA in urine samples by solid-phase microextraction and gas chromatography-mass spectrometry in selected ion monitoring%尿中苯丙胺、甲基苯丙胺、MDA和MDMA的固相微萃取和GC/MS/SIM测定

    Institute of Scientific and Technical Information of China (English)

    张绍雨; 黄增萍

    2005-01-01

    目的研究固相微萃取(SPME)用于尿中苯丙胺(AMP)、甲基苯丙胺(MET)、3,4-亚甲二氧基苯丙胺(MDA)和3,4-亚甲二氧基甲基苯丙胺(MDMA)的提取.方法样品调节至碱性和用盐饱和后用顶空SPME,内标为MET-d5.萃取纤维为100μm聚二甲基硅氧烷(PDMS).用气质联用选择离子检测(GC/MS/SIM).结果0.2μg/ml加标尿样,AMP、MET、MDA和MDMA的富集倍数分别为22,60,13和47.检出限(S/N=3)为0.4~9.5 ng/ml.线性范围为0.05~1μg/ml.0.2、0.5和1.0μg/ml加标尿样,相对回收率77.9%~112.4%,变异系数2.7%~18.0%(n=5).用该方法分析5个案件样品,和常规液液萃取结果接近.结论顶空SPME法用于尿中AMP、MET、MDA和MDMA等化合物的分析,无需有机溶剂,富集效率高,提取-富集-进样一体化,简单方便实用.

  10. 苯丙胺类兴奋剂滥用后性行为及相关性行为特征变化的流行病学调查%THE POPULATION CHARACTERISTICS AND CHANGES OF SEXUAL BEHAVIORS AFTER AMPHETAMINE TYPE STIMULANTS ABUSE

    Institute of Scientific and Technical Information of China (English)

    闫世艳; 曲直; 张浩然; 王清亮; 连智; 鲍彦平; 刘志民

    2013-01-01

    目的:调查我国苯丙胺类兴奋剂滥用人群特征及滥用后性行为及相关性行为特征的变化.方法:采用回顾性自身前后对照设计,以课题组自拟调查问卷为工具,对符合调查对象入选要求、且甲基苯丙胺或3,4-亚甲基二氧甲基苯丙胺尿液毒品检测阳性的调查对象进行调查.结果:本调查共收集有效问卷394份,调查对象中75.1%为男性,20-30 a和30-40 a所占的比例分别为47.2%和35.0%.滥用涉及各类群体,但以私营或个体劳动者(31.9%)和无业(41.7%)为主.调查对象的中位累计滥用时间为8个月,主要滥用方式为烫吸(97.7%).苯丙胺类兴奋剂滥用后性活动变化明显,表现为出现性冲动(63.5%)、性欲增强(35.0%)、性活动频率增加以及性活动持续时间延长(61.3%)等现象.调查结果还表明20.8%的调查对象滥用苯丙胺类兴奋剂后经常发生性行为,9.0%几乎每次都发生,分别有36.1%和21.7%的调查对象会与一起用药的人、性服务工作者发生性关系.此外,8例调查对象报告与同性发生过性关系;6例报告发生过性暴力;6例报告发生过性交易.按照性别和滥用剂量进行分层分析后发现,男性与女性在滥用苯丙胺类兴奋剂后的性行为及性行为相关特征有一定差异.结论:苯丙胺类兴奋剂滥用后性活动变化明显,提示苯丙胺类兴奋剂滥用对性行为可能有刺激作用.另外,男性和女性在滥用后均表现出性兴奋的特征,但男性的性活动比女性更活跃.对不同滥用剂量分组后进行相关性行为差别的分析分层分析[B1]结果提示苯丙胺类兴奋剂滥用与对性行为的刺激作用之间可能存在一定的剂量-反应关系.本研究的结论均来自患者自我报告,尚需进一步研究证实.

  11. 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

    OpenAIRE

    Marcelo Carvalho Lasmar; Edna Maria Alvarez Leite

    2007-01-01

    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 n...

  12. Chemistry, pharmacology, and metabolism of emerging drugs of abuse.

    Science.gov (United States)

    Maurer, Hans H

    2010-10-01

    In recent years, besides the classic designer drugs of the amphetamine type, a series of new drug classes appeared on the illicit drugs market. The chemistry, pharmacology, toxicology, metabolism, and toxicokinetics is discussed of 2,5-dimethoxy amphetamines, 2,5-dimethoxy phenethylamines, beta-keto-amphetamines, phencyclidine derivatives as well as of herbal drugs, ie, Kratom. They have gained popularity and notoriety as rave drugs. The metabolic pathways, the involvement of cytochrome P450 isoenzymes in the main pathways, and their roles in hepatic clearance are also summarized. PMID:20683389

  13. 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.

  14. 76 FR 55616 - Schedules of Controlled Substances: Temporary Placement of Three Synthetic Cathinones Into...

    Science.gov (United States)

    2011-09-08

    ... and pharmacologically similar to amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), cathinone and... are similar to those of methamphetamine, cathinone, methcathinone, and MDMA, the abuse of synthetic... cocaine, methamphetamine, and MDMA. Although synthetic cathinones are new to the United States'...

  15. Treat Jail Detainees' Drug Abuse to Lower HIV Transmission

    Science.gov (United States)

    ... To Lower HIV Transmission Study: Treat Jail Detainees’ Drug Abuse To Lower HIV Transmission Email Facebook Twitter March ... Treatment Research Trends and Statistics Women and Drugs Drugs of Abuse Alcohol Amphetamines Bath Salts Brain and Addiction Club ...

  16. 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.

    2014-01-01

    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, b

  17. 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.

    2014-01-01

    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,

  18. 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.

  19. Malignant hyperthermia

    Science.gov (United States)

    Repeated or untreated episodes can cause kidney failure. Untreated episodes can be fatal. ... such as cocaine, amphetamine (speed), and ecstasy. These drugs may cause problems similar to malignant hyperthermia in people who ...

  20. Eucalyptus

    Science.gov (United States)

    ... with a combination of eucalyptus oil, lavender, marjoram, rosemary, and peppermint oils might reduce pain and depression ... ModerateBe cautious with this combination.Talk with your health provider.AmphetaminesInhaling eucalyptol, a chemical found in eucalyptus ...

  1. Drugs: Shatter the Myths

    Science.gov (United States)

    ... brain chemicals called: A. . neurons B. . axons C. . neurotransmitters D. . dendrites What is NOT true about “bath ... E. . Both a and b. 25 ANSWERS: C. Neurotransmitters, C. “Bath salts”often contain amphetamine-like chemicals ...

  2. Rohypnol

    Science.gov (United States)

    ... or willingly taking Rohypnol can receive the same punishment as users of Schedule I drugs ( LSD , heroin), ... THIS TOPIC Drugs: What to Know Dealing With Addiction Date Rape MDMA (Ecstasy) Amphetamines GHB Ketamine School ...

  3. 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

  4. Analysis of Drugs of Abuse in Anonymously Collected Urine and Soil samples from a Music Festival in Scandinavia

    DEFF Research Database (Denmark)

    Mardal, Marie; Ramin, Pedram; Plósz, Benedek G.;

    -MS Results: In the urine samples, the following compounds (and their metabolites) could be detected: cocaine (in 13 samples), levamisole (11), MDMA (9), amphetamine (2), and methamphetamine (2). Furthermore, therapeutic drugs such as metoprolol, carbamazepine, citalopram, quetiapine, methylphenidate...

  5. 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...

  6. Hallucinations

    Science.gov (United States)

    ... high, or coming down from such drugs like marijuana , LSD , cocaine (including crack), PCP, amphetamines, heroin, ketamine, ... do a physical examination and take a medical history. They will also ask you questions about your ...

  7. Nationwide Trends

    Science.gov (United States)

    ... Methamphetamine Prescription and Over-the-Counter Medications Stimulant ADHD Medications: Methylphenidate and Amphetamines Synthetic Cannabinoids Synthetic Cathinones ("Bath Salts") Effects of Drug Abuse Comorbidity: Addiction and Other Mental Disorders Drugged Driving HIV/ ...

  8. Toxic Effects of Opioid and Stimulant Drugs on Undifferentiated PC12 Cells

    OpenAIRE

    Oliveira, M Teresa; Rego, A. Cristina; Morgadinho, M Teresa; Macedo, Tice R; Oliveira, Catarina R.

    2012-01-01

    Cell death and reactive oxygen species production have been suggested to be involved in neurodegeneration induced by the drugs of abuse. In this study we analyze the toxicity of the following drugs of abuse: heroin, morphine, d-amphetamine, and cocaine in undifferentiated PC12 cells, used as dopaminergic neuronal models. Our data show that opioid drugs (heroin and morphine) are more toxic than stimulant drugs (d-amphetamine and cocaine). Toxic effects induced by heroin are associated with a d...

  9. On the Role of Cannabinoid CB1- and μ-Opioid Receptors in Motor Impulsivity

    OpenAIRE

    Wiskerke, Joost; van Mourik, Yvar; Schetters, Dustin; Schoffelmeer, Anton N. M.; Pattij, Tommy

    2012-01-01

    Previous studies using a rat 5-choice serial reaction time task have established a critical role for dopamine D2 receptors in regulating increments in motor impulsivity induced by acute administration of the psychostimulant drugs amphetamine and nicotine. Here we investigated whether cannabinoid CB1 and/or μ-opioid receptors are involved in nicotine-induced impulsivity, given recent findings indicating that both receptor systems mediate amphetamine-induced motor impulsivity. Results showed th...

  10. On the role of cannabinoid CB1- and µ-opioid receptors in nicotine-induced motor impulsivity

    OpenAIRE

    TommyPattij

    2012-01-01

    Previous studies using a rat 5-choice serial reaction time task (5-CSRTT) have established a critical role for dopamine D2 receptors in regulating increments in motor impulsivity induced by acute administration of the psychostimulant drugs amphetamine and nicotine. Here we investigated whether cannabinoid CB1 and/or µ-opioid receptors are involved in nicotine-induced impulsivity, given recent findings indicating that both receptor systems mediate amphetamine-induced motor impulsivity. Re...

  11. Role of monoamine systems in activation of zif268 by cocaine.

    OpenAIRE

    Bhat, R V; Cole, A J; Baraban, J M

    1992-01-01

    Rapid activation of transcription factor genes is thought to play a key role in stimulus-induced neuronal plasticity. To help understand the genomic response that may underlie long-term effects of cocaine and amphetamine, we have investigated the effect of these agents on Zif268, a transcription regulatory factor that is expressed at high levels in brain neurons. Like c-fos, zif268 is markedly activated in striatum by cocaine and amphetamine. This response appears to involve the dopamine syst...

  12. Assessing Correlates of the Growth and Extent of Methamphetamine Abuse and Dependence in California

    OpenAIRE

    Gruenewald, Paul J.; Johnson, Fred W.; Ponicki, William R.; Remer, Lillian G.; LaScala, Elizabeth A.

    2010-01-01

    Using aggregate-level data, this study performed cross-sectional analyses on all 1,628 populated California zip code areas and longitudinal analyses on 581 consistently defined zip codes over six years (1995– 2000), relating place and population characteristics of these areas to rates of hospital discharges for amphetamine dependence/abuse using linear spatial models. Analyzing the data in two ways, spatial time series cross-sections and spatial difference models, amphetamin...

  13. Semiautomated radioimmunoassay for mass screening of drugs of abuse

    International Nuclear Information System (INIS)

    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

  14. The contribution of dopamine and norepinephrine transporters to psychostimulant-induced memory enhancement /

    OpenAIRE

    Carmack, Stephanie Ann

    2014-01-01

    The psychostimulants methylphenidate and amphetamine enhance monoaminergic neurotransmission by acting on reuptake transporters. Together, they form the cornerstone of treatment for attention-deficit hyperactivity disorder, the most common psychiatric disorder in children, because of their ability to improve learning at low doses. At high doses, they are subject to abuse that can lead to addiction and cognitive dysfunction. Current theories posit that methylphenidate and amphetamine exert the...

  15. Amygdala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes.

    OpenAIRE

    Packard, M G; L. Cahill; McGaugh, J L

    1994-01-01

    These experiments investigated the effects, on memory, of injections of d-amphetamine (10 micrograms/0.5 microliter) administered into the amygdala, hippocampus, or caudate nucleus immediately after training in cued or spatial water-maze tasks. In experiment 1, rats received an eight-trial training session on one of the two tasks followed by injections of d-amphetamine or saline. Retention was tested 24 hr later. On the spatial task, intrahippocampal, but not intracaudate, injections of d-amp...

  16. Clinical and Neurobiological Aspects of Narcolepsy

    OpenAIRE

    Nishino, Seiji

    2007-01-01

    Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy and/or other dissociated manifestations of rapid eye movement (REM) sleep (hypnagogic hallucinations and sleep paralysis). Narcolepsy is currently treated with amphetamine-like central nervous system (CNS) stimulants (for EDS) and antidepressants (for cataplexy). Some other classes of compounds such as modafinil (a non-amphetamine wake-promoting compound for EDS) and gamma-hydroxybutyrate (GHB, a short-acting sedativ...

  17. HEALTH AND SOCIO-ECONOMIC HAZARDS ASSOCIATED WITH KHAT CONSUMPTION

    OpenAIRE

    Hussein M. A. Ageely

    2008-01-01

    The consumption of the stimulant leaf Khat (Catha edulis Forsk) is widespread in several countries of East Africa and the Arabian Peninsula. The leaf comes from a small evergreen shrub that can grow to the size of a tree. Young buds and tender leaves are chewed to attain a state of euphoria and stimulation. Khat leaves contain cathinones, an active brain stimulant that is similar in structure and pharmacological activity to amphetamines. Like amphetamines, Khat ingestion in low doses results ...

  18. [Fatal poisoning due to narcotic abuse in the analytic-toxicological practice of Forensic Medicine Department Silesian Medical Academy in Katowice in years 1996-202].

    Science.gov (United States)

    Soja, Artur; Celiński, Rafał; Kulikowska, Joanna; Albert, Małgorzata; Sybirska, Halina

    2003-01-01

    147 cases of fatal poisonings in people due to narcotic abuse examined in the Forensic Medicine Department Silesian School of Medicine, Katowice in the years 1996-2002 have been presented in the paper. In the group examined there were 126 males and 21 females at the age of 16-44. Opium narcotics were found in 139 out of 147 cases and amphetamine derivatives in 18. Opiates were indicated in 58 individuals and amphetamine only in 8. In 35 poisoned people opiates with barbituric acid derivatives were found. In 3 cases death resulted after taking opiates and amphetamine derivatives. 1 individual died after taking opiates and substances of the phenothiazine group. In the organic fluids of 18 people opiates and medicines being derivatives of 1,4-benzodiazepine and barbituric acid were found. Amphetamine and derivatives of 1,4-benzodiazepine were found in 6 individuals and opiates, barbiturates, benzodiazepines and amphetamine in 1 individual. Concentrations of all the substances indicated ranged widely and were as follows: microgram/ml for opiates; microgram/ml for amphetamine; microgram/ml for 1.4-benzodiazepine derivatives and microgram/ml for barbituric acid derivatives. Ethanol was found in 18 individuals and its concentration was @1000. PMID:14669548

  19. Hyphenated GC-FTIR and GC-MS techniques applied in the analysis of bioactive compounds

    Science.gov (United States)

    Gosav, Steluta; Paduraru, Nicoleta; Praisler, Mirela

    2014-08-01

    The drugs of abuse, which affect human nature and cause numerous crimes, have become a serious problem throughout the world. There are hundreds of amphetamine analogues on the black market. They consist of various alterations of the basic amphetamine molecular structure, which are yet not yet included in the lists of forbidden compounds although they retain or slightly modify the hallucinogenic effects of their parent compound. It is their important variety that makes their identification quite a challenge. A number of analytical procedures for the identification of amphetamines and their analogues have recently been reported. We are presenting the profile of the main hallucinogenic amphetamines obtained with the hyphenated techniques that are recommended for the identification of illicit amphetamines, i. e. gas chromatography combined with mass spectrometry (GC-MS) and gas chromatography coupled with Fourier transform infrared spectrometry (GC-FTIR). The infrared spectra of the analyzed hallucinogenic amphetamines present some absorption bands (1490 cm-1, 1440 cm-1, 1245 cm-1, 1050 cm-1 and 940 cm-1) that are very stable as position and shape, while their intensity depends of the side-chain substitution. The specific ionic fragment of the studied hallucinogenic compounds is the 3,4-methylenedioxybenzyl cation (m/e = 135) which has a small relative abundance (lesser than 20%). The complementarity of the above mentioned techniques for the identification of hallucinogenic compounds is discussed.

  20. The effect of antimotion sickness drugs on habituation to motion

    Science.gov (United States)

    Wood, C. D.; Manno, J. E.; Manno, B. R.; Odenheimer, R. C.; Bairnsfather, L. E.

    1986-01-01

    The mechanism which allows for increased exposure to motion and accelerates habituation is investigated. The responses of 12 male and female subjects between 18-30 years rotated once a day for 5 days on the Contraves Goerz rotating chair after receiving placebo, 10 mg d-amphetamine, 0.6 mg scopolamine with 5 mg d-amphetamine, and 1.0 mg scopolamine are studied. It is observed that with placebo the subjects performed 48 more head movements than untreated subjects, 118 more movements with d-amphetamine, 176 more with 0.6 mg scopolamine with d-amphetamine, and 186 more with 1.0 scopolamine. The data reveal that exposure to rotation increases tolerance from 88 head movements on day 2 to 159 on day 4 at 17.4 rpm and with placebo; 96 to 186 at 19.9 rpm with 10 mg d-amphetamine; 111 to 273 at 20.2 rpm with scopolamine with d-amphetamine, and 141 to 279 at 22.4 rpm with 1.0 mg scopolamine. It is noted that a combination of cholinergic blocking and norepinephrine activation action is most effective in preventing the development of motion sickness and habituation is due to the greater exposure to vestibular simulation permitted by the drugs.

  1. Analysis of forensic samples of "Ecstasy" tablets seized in Novi Sad during the 2004 year

    Directory of Open Access Journals (Sweden)

    Zgonjanin Dragana M.

    2005-01-01

    Full Text Available The paper presents results of the analysis of illicit synthetic drugs in the form of tablets distributed under the name "Ecstasy", seized by the police in the broader area of Novi Sad 2004. A huge number of tablets has been analyzed (n=121, of various colours and with impressed symbols from the total amount of 93 seizures, which totally amounted to 1458 tablets. Regarding the number of seizures ecstasy (3,4-methylendioxy-N-meth-yl-amphetamine - MDMA is dominant among all, and according to the quantity of seized tablets it is amphetamine (AP, while other amphetamine-type drugs (methamphetamine MA 3,4-methylendioxiamphetamine - MDA, 3,4-methylendioxi-N-ethyl-amphetamine MDEA have been found in rather small quantities and very rarely. Tablets mostly contain caffeine as an additive. In the analytical procedure, the samples of tablets were subjected to liquid-liquid extraction and afterwards analyzed on the GCD (GC-EI Hewlett-Packard instrument. The method is fast reliable and reproducible for the analysis of amphetamine, methamphetamine MDA, MDMA, MDEA, as well as various additives in the samples of seized tablets.

  2. Mephedrone: Public health risk, mechanisms of action, and behavioral effects.

    Science.gov (United States)

    Dybdal-Hargreaves, Nicholas F; Holder, Nicholas D; Ottoson, Paige E; Sweeney, Melanie D; Williams, Tyisha

    2013-08-15

    The recent shortage of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) has led to an increased demand for alternative amphetamine-like drugs such as the synthetic cathinone, 4-methylmethcathinone (mephedrone). Despite the re-classification of mephedrone as a Class B restricted substance by the United Kingdom and restrictive legislation by the United States, international policy regarding mephedrone control is still developing and interest in synthetic amphetamine-like drugs could drive the development of future mephedrone analogues. Currently, there is little literature investigating the mechanism of action and long-term effects of mephedrone. As such, we reviewed the current understanding of amphetamines, cathinones, and cocaine emphasizing the potentially translational aspects to mephedrone, as well as contrasting with the work that has been done specifically on mephedrone in order to present the current state of understanding of mephedrone in terms of its risks, mechanisms, and behavioral effects. Emerging research suggests that while there are structural and behavioral similarities of mephedrone with amphetamine-like compounds, it appears that serotonergic signaling may mediate more of mephedrone's effects unlike the more dopaminergic dependent effects observed in traditional amphetamine-like compounds. As new designer drugs are produced, current and continuing research on mephedrone and other synthetic cathinones should help inform policymakers' decisions regarding the regulation of novel 'legal highs.' PMID:23764466

  3. Pharmacotherapy of methamphetamine addiction: an update.

    Science.gov (United States)

    Elkashef, Ahmed; Vocci, Frank; Hanson, Glen; White, Jason; Wickes, Wendy; Tiihonen, Jari

    2008-01-01

    Methamphetamine dependence is a serious public health problem worldwide for which there are no approved pharmacological treatments. Psychotherapy is still the mainstay of treatment; however, relapse rates are high. The search for effective pharmacological treatment has intensified in the last decade. This review will highlight progress in pharmacological interventions to treat methamphetamine dependence as well as explore new pharmacological targets. Published data from clinical trials for stimulant addiction were searched using PubMed and summarized, as well as highlights from a recent symposium on methamphetamine pharmacotherapy presented at the ISAM 2006 meeting, including interim analysis data from an ongoing D-amphetamine study in Australia. Early pilot data are encouraging for administering D-amphetamine and methylphenidate as treatment for heavy amphetamine users. Abilify at 15 mg/day dose increased amphetamine use in an outpatient pilot study. Sertraline, ondansetron, baclofen, tyrosine, and imipramine were ineffective in proof-of-concept studies. Development of pharmacotherapy for methamphetamine dependence is still in an early stage. Data suggesting D-amphetamine and methylphenidate as effective pharmacotherapy for methamphetamine addiction will need to be confirmed by larger trials. Preclinical data suggest that use of GVG, CB1 antagonist, and lobeline are also promising therapeutic strategies. PMID:19042205

  4. Profiles and changes in stimulant use in Belgium in the period of 2011-2015.

    Science.gov (United States)

    Been, Frederic; Lai, Foon Yin; Kinyua, Juliet; Covaci, Adrian; van Nuijs, Alexander L N

    2016-09-15

    Adapting illicit drug policy strategies requires detailed knowledge on types and amounts of substances consumed by the target population. In this study, we applied wastewater-based epidemiology to detect spatio-temporal changes in the relative amounts of stimulants (amphetamine, methamphetamine, methylenedioxymethamphetamine (MDMA), cocaine) used in seven locations in Belgium over 2011-2015. Clear geographical differences were observed with stimulant users in large cities (Antwerp, Brussels) showing a preference for cocaine, while amphetamine use was most abundant in smaller cities (Geraardsbergen, Koksijde, Lier, Ninove, Ostend). Results obtained across õdifferent years revealed that the investigated substances had a stable share in the total amount of stimulants used, suggesting that habits of stimulant use remained constant, although differences in absolute amounts were observed across years. Investigation of the weekly pattern in stimulant use showed an increase in the use of MDMA on the weekends compared to cocaine and amphetamine. PMID:27251771

  5. Drug-related death in Denmark in 2007

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Hansen, A. Carsten; Rollmann, Dorte;

    2011-01-01

    number of drug-related deaths in 2007 was 226. Methadone deaths had increased since 1997 while heroin/morphine deaths decreased. In earlier studies, very few deaths from central stimulants like cocaine and amphetamines occurred (1-1.5%), but in 2007 6% of the deaths were caused by these drugs. Multiple...... drug use was common. Heroin/morphine, cocaine, amphetamine, cannabis, methadone, benzodiazepines and alcohol were included in the poly-drug use. CONCLUSION: This investigation shows stabilization in the number of fatal poisonings in drug addicts. Geographic differences were observed. Methadone was the...... most frequent cause of fatal poisoning and there was a continuous decrease in heroin/morphine deaths. Fatal deaths from cocaine and amphetamine have increased considerably. Multiple drug use was common....

  6. Antimanic efficacy of retigabine in a proposed mouse model of bipolar disorder

    DEFF Research Database (Denmark)

    Nielsen, Ditte Dencker; Bak-Jensen, Henriette Husum

    2010-01-01

    Retigabine is a novel compound with anticonvulsant efficacy. Preclinical studies have indicated that the compound, like other anticonvulsants may also have antimanic efficacy. Bipolar disorder is characterized by episodes of depression and mania, which show a progressively faster recurrence and an...... increase in severity with time. Recurrence of episodes in bipolar disorders is suggested to reflect a process of sensitization. Repeated intermittent administration of amphetamine in rodents gives rise to a behavioral sensitization phenomena argued to have similarities to the sensitization found in humans....... The aims were therefore to explore the predictive validity of the amphetamine sensitization model as a behavioral model of mania by testing the effect of a range of antimanic drugs and to evaluate the effect of retigabine on the sensitized amphetamine response. Furthermore, since withdrawal from...

  7. Drug use in college students: a 13-year trend

    Directory of Open Access Journals (Sweden)

    Gabriela Arantes Wagner

    2012-06-01

    Full Text Available OBJECTIVE: To analyze drug use trends among college students in 1996, 2001 and 2009. METHODS: A cross-sectional epidemiological study with a multistage stratified cluster sample with 9,974 college students was conducted in the city of São Paulo, southeastern Brazil. An anonymous self-administered questionnaire was used to collect information on drug use assessed in lifetime, the preceding 12 months and the preceding 30 days. The Bonferroni correction was used for multiple comparisons of drug use rates between surveys. RESULTS: There were changes in the lifetime use of tobacco and some other drugs (hallucinogens [6.1% to 8.8%], amphetamines [4.6% to 8.7%], and tranquilizers [5.7% to 8.2%] from 1996 to 2009. Differences in the use of other drugs over the 12 months preceding the survey were also seen: reduced use of inhalants [9.0% to 4.8%] and increased use of amphetamines [2.4% to 4.8%]. There was a reduction in alcohol [72.9% to 62.1%], tobacco [21.3% to 17.2%] and marijuana [15.0% to 11.5%] use and an increase in amphetamine use [1.9% to 3.3%] in the preceeding 30 days. CONCLUSIONS: Over the 13-year study period, there was an increase in lifetime use of tobacco, hallucinogens, amphetamines, and tranquilizers. There was an increase in amphetamine use and a reduction in alcohol use during the preceding 12 months. There was an increase in amphetamine use during the preceding 30 days.

  8. Effects of the 5-HT3 receptor antagonist, GR38032F, on raised dopaminergic activity in the mesolimbic system of the rat and marmoset brain.

    OpenAIRE

    Costall, B; Domeney, A M; Naylor, R J; Tyers, M. B.

    1987-01-01

    1 The ability of the selective 5-HT3 receptor antagonist GR38032F to reduce raised mesolimbic dopaminergic activity was studied in behavioural experiments in the rat and marmoset. 2 GR38032F injected into the nucleus accumbens (0.01-1 ng) or peripherally (0.01-1 mg kg-1 i.p.) inhibited the locomotor hyperactivity caused by the acute intra-accumbens injection of amphetamine (10 micrograms) in the rat. Similar treatments with sulpiride and fluphenazine also inhibited the amphetamine-induced hyp...

  9. Fatal poisoning among patients with drug addiction

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Christoffersen, Dorte J; Banner, Jytte;

    2015-01-01

    2012 were included in the study. RESULTS: A total of 188 fatal intoxications were recorded. The median age increased from 37.5 in 2007 to 41.5 in 2012. The majority were men (77%). Methadone (59%) was the main intoxicant. The decrease in the frequency of heroin/morphine deaths since 1997 (71......%) continued, declining to 44% in 2002, 33% in 2007 and finally to 27% in 2012. Few deaths from central stimulants (amphetamine and cocaine) occurred. Multiple drug use was common and consisted mainly of opioids, cocaine, amphetamine, cannabis, benzodiazepines and alcohol. Heroin/morphine use was most frequent...

  10. Is the Use of Ecstasy and Hallucinogens Increasing?

    OpenAIRE

    Schuster, Peter; Lieb, Roselind; Lamertz, Christina; Wittchen, Hans-Ulrich

    2012-01-01

    This report presents findings of a community survey of 3,021 adolescents and young adults aged 14–24 years in Munich, Germany, carried out to determine the prevalence of use and abuse of and dependence on ecstasy, amphetamines and hallucinogens. The response rate was 71%. Results: (1) In 1995, 4% of the male and 2.3% of the female respondents aged 14–24 reported the use of ecstasy. Ecstasy-related substances (amphetamines and chemically related substances) were reported by 3.6% of men and ...

  11. Benfluorex: increasing reports of valve disorders.

    Science.gov (United States)

    2010-02-01

    Benfluorex is an amphetamine appetite suppressant derived from fenfluramine. In France, about 30 cases of pulmonary arterial hypertension and a similar number of valve disorders, often involving several valves, were reported between 1998 and 2009. Benfluorex has the same adverse effects as those that led to the withdrawal of amphetamine appetite suppressants such as fenfluramine.There is no proven benefit that justifies exposing patients to these risks. The French National Pharmacovigilance Committee simply proposed "to await the results of planned and ongoing studies". However, it would be in patients' best interests to withdraw this drug from the market. PMID:20455335

  12. Enantiomeric profiling of chiral drug biomarkers in wastewater with the usage of chiral liquid chromatography coupled with tandem mass spectrometry.

    Science.gov (United States)

    Castrignanò, Erika; Lubben, Anneke; Kasprzyk-Hordern, Barbara

    2016-03-18

    This paper proposes a novel multi-residue enantioselective method utilising a CBH (cellobiohydrolase) column, for the analysis of 56 drug biomarkers in wastewater. These are: opioid analgesics, amphetamines, cocaine, heroin, stimulants, anaesthetics, sedatives, anxiolytics, designer drugs, phosphodiesterase-5 (PDE5) inhibitors, amphetamine and methamphetamine drug precursors. Satisfactory enantiomeric separation was obtained for 18 pairs of enantiomers including amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and its metabolites HMA (4-hydroxy-3-methoxyamphetamine) and HMMA (4-hydroxy-3-methoxy-methamphetamine), PMA (para-methoxyamphetamine), MDA ((±)- 3,4-methylenedioxyamphetamine) and mephedrone. The method was applied in a one week monitoring study of a large wastewater treatment plant in the UK. Most target drugs were found at quantifiable concentrations in analysed samples. Enantiomeric profiling revealed that amphetamine, methamphetamine and MDMA were found enriched with R-(-)-enantiomers, probably due to their stereoselective metabolism favouring S-(+)-enantiomers. MDA was either enriched with R-(-)- or S-(+)-enantiomer indicating that its presence might be due to either abuse of racemic MDA or abuse of racemic MDMA respectively. Non-racemic enantiomeric fractions were also observed in the case of HMMA and mephedrone suggesting enantioselective metabolism. To the authors' knowledge, this is the first time chiral separation and wastewater profiling of mephedrone, PMA, MDMA and its metabolites HMA and HMMA have been reported. PMID:26896918

  13. Drug: D02074 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02074 Drug Amphetamine sulfate (USP); Benzedrine (TN) (C9H13N)2. H2SO4 368.177 368.4909 D02074. ... OANALEPTICS N06B PSYCHOSTIMULANTS, AGENTS USED FOR ADHD ... AND NOOTROPICS N06BA Centrally acting sympathomime ...

  14. Drug: D07445 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07445 Drug Amfetamine (INN); Amphetamine; Amfetamin (TN) C9H13N 135.1048 135.2062 D07445.gif Ps ... OANALEPTICS N06B PSYCHOSTIMULANTS, AGENTS USED FOR ADHD ... AND NOOTROPICS N06BA Centrally acting sympathomime ...

  15. Pre and postprandial changes in orexigenic and anorexigenic factors in channel catfish Ictalurus punctatus

    Science.gov (United States)

    Ghrelin (GRLN), cocaine and amphetamine regulated transcript (CART), neuropeptide Y (NPY), and cholecystokinin (CCK) are neuropeptides involved in the regulation of appetite and feeding in vertebrates. We examined pre- and postprandial changes in the expression of plasma GHRL and mRNAs encoding GRL...

  16. Conflict Between Maternal Autonomy and Child Health in Substance-use

    Science.gov (United States)

    2016-06-14

    Substance-Related Disorders; Alcohol-Related Disorders; Amphetamine-Related Disorders; Inhalant Abuse; Cocaine-Related Disorders; Opioid-Related Disorders; Marijuana Abuse; Substance Abuse, Intravenous; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy, High-Risk; Prenatal Education; Antenatal Parenthood Education; Antenatal Education; Health Personnel

  17. Comparison study of two different procedures for the determination of drugs of abuse in postmortem brain samples

    DEFF Research Database (Denmark)

    Holm, Karen Marie Dollerup; Reiter, Birgit; Skov, Louise;

    2014-01-01

    from blood to brain and thereby see if we could avoid a time comsuming optimization of the Copenhagen method to accommodate the more complex brain matrix. Comparative analyses and quantification of eight drugs of abuse (methadone, morphine, amphetamine, benzoylecgonine, cocaine, morphine, codeine...

  18. HYPERACTIVITY AND HYPOACTIVITY PRODUCED BY LESIONS TO THE MESOLIMBIC DOPAMINE SYSTEM

    Science.gov (United States)

    Spontaneous locomotor activity and the locomotor response to amphetamine and apomorphine were studied in rats subjected to either radiofrequency(RF), 6-hydroxydopamine (6-OHDA) of both RF and 6-OHDA lesions of the mesolimbic dopamine (DA) system. Large 6-OHDA lesions of the ventr...

  19. Forgiftningsdødsfald blandt narkomaner i Fyns Amt i 1995 og 1996

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Andersen, Lis Sahl; Jensen, Britt Toftgård;

    1999-01-01

    discussed. The study included 47 drug addicts. Median age was 34, age span: 20-43. The main cause of death was poisoning by heroin. In 28% of the drug addicts cocaine was detected and in 13% amphetamine. About half had used benzodiazepines. Few were employees, most were criminals and eight were homeless...

  20. Asymptomatic body packers should be treated conservatively

    DEFF Research Database (Denmark)

    Glovinski, Peter V; Lauritsen, Morten L; Bay-Nielsen, Morten;

    2013-01-01

    Body packing takes advantage of the human storage capacity within the alimentary tract. Body packing is used for the smuggling of drugs such as heroin, cocaine, amphetamine, hashish and ecstasy. Most body packers are asymptomatic. However, packets may rupture or obstruct the alimentary tract...

  1. Single Molecule Imaging of Conformational Dynamics in Sodium-Coupled Transporters

    Science.gov (United States)

    Terry, Daniel S.

    2013-01-01

    Neurotransmitter:sodium symporter (NSS) proteins remove neurotransmitters released into the synapse through a transport process driven by the physiological sodium ion (Na[superscript +]) gradient. NSSs for dopamine, noradrenaline, and serotonin are targeted by the psychostimulants cocaine and amphetamines, as well as by antidepressants. The…

  2. Safety, Efficacy, and Legal Issues Related to Dietary Supplements

    Science.gov (United States)

    Powers, Michael

    2004-01-01

    This article focuses on the effects of dietary supplements on collegiate and adult populations. Anabolic steroids, amphetamines, and other drugs have been used for decades to improve athletic performance. However, the legal issues and dangers associated with these drugs have resulted in reluctance by many athletes to use them. Because dietary…

  3. MDMA (Ecstasy or Molly)

    Science.gov (United States)

    ... found to contain caffeine, dextromethorphan (found in some cough syrups), amphetamines, PCP, or cocaine. How does MDMA affect ... Drug Facts Alcohol Anabolic Steroids Bath Salts Cocaine Cough and Cold Medicine (DXM and Codeine Syrup) Heroin Inhalants Marijuana MDMA (Ecstasy or Molly) Methamphetamine ( ...

  4. Polymorphism within thyroid hormone responsive (THRSP) associated with weaning-to-oestrus interval in swine

    Science.gov (United States)

    The objective of this study was to assess polymorphisms within lipogenic-related candidate genes for association with the reproductive traits; age at puberty (AP), ovulation rate (OR), and weaning-to-estrus interval (WEI). Variations within the anorectic gene Cocaine- and Amphetamine-Regulated Trans...

  5. Cart Regulates Food Intake 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 ...

  6. Effects of the Psychoactive Drug: Methylphenidate (Ritalin) on Classroom Disorders: Hyperactivity, Emotional Disturbance and Learning Disorders.

    Science.gov (United States)

    Hirst, Irene

    Reviewed were several research studies using varying dosages of methylphenidate (Ritalin) in contrast with thioridazine and amphetamine under various behavioral conditions and situations with hyperactive, emotionally disturbed, and learning disabled children. Results from the studies with hyperactive children indicated that drug treatment was…

  7. What Exactly Are the Benefits of Stimulants for ADHD?

    Science.gov (United States)

    Advokat, Claire

    2009-01-01

    Stimulant drugs (methylphenidate and amphetamine) have been used successfully for decades to improve the behavioral impairments of hyperactivity, impulsivity, and inattention in children diagnosed with attention-deficit/hyperactivity disorder (ADHD). A voluminous literature supports the benefits of stimulants for improving classroom manageability…

  8. CHARACTERIZING THE PSYCHOLOGICAL STATE PRODUCED BY LSD.

    Science.gov (United States)

    KATZ, MARTIN M.; AND OTHERS

    THE DEVELOPMENT AND COMPONENTS OF LYSERGIC ACID DIETHYLAMIDE (LSD) PRODUCED PSYCHOLOGICAL STATES ARE INVESTIGATED. THE SUBJECTS WERE PAID VOLUNTEERS FROM THE PATUXENT INSTITUTION, A TREATMENT CENTER FOR EMOTIONALLY UNSTABLE CRIMINAL OFFENDERS. IN ONE STUDY, GROUPS OF 23 SUBJECTS RECEIVED LSD, AN AMPHETAMINE, OR A PLACEBO. IN THE SECOND STUDY, 11…

  9. Cocaine strongly reduces prepulse inhibition in apomorphine-susceptible rats, but not in apomorphine-unsusceptible rats: regulation by dopamine D2 receptors.

    NARCIS (Netherlands)

    Elst, M.C.J. van der; Ellenbroek, B.A.; Cools, A.R.

    2006-01-01

    Dopaminergic agonists, such as apomorphine and amphetamine, have been shown to drastically reduce prepulse inhibition of the acoustic startle reflex. The effects of the indirect dopamine agonist cocaine on prepulse inhibition have only been described in a few reports and have yielded conflicting res

  10. "Lookalike" Drugs. Specialized Information Service.

    Science.gov (United States)

    Do It Now Foundation, Phoenix, AZ.

    The document presents a collection of articles about "lookalike drugs." Article 1 presents readers with a look at "peashooters" (lookalike drugs which are usually replicas of pharmaceutical amphetamines, but increasingly used to describe simulations of cocaine and prescription downers). Lookalikes, although usually legal, are seen as a danger for…

  11. Mitochondrial respiratory dysfunction due to the conversion of substituted cathinones to methylbenzamides in SH-SY5Y cells.

    Science.gov (United States)

    den Hollander, Bjørnar; Sundström, Mira; Pelander, Anna; Siltanen, Antti; Ojanperä, Ilkka; Mervaala, Eero; Korpi, Esa R; Kankuri, Esko

    2015-01-01

    The increased use of cathinone-type designer drugs, known as legal highs, has led to concerns about their potential neurotoxicity due to their similarity to methamphetamine (METH). Therefore, closer investigations of their toxic effects are needed. We investigated the effects of the cathinones 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxymethcathinone (MDMC) and the amphetamine METH on cytotoxicity and mitochondrial respiration in SH-SY5Y neuroblastoma cells. We also investigated the contribution of reactive species, dopamine, Bcl-2 and tumor necrosis factor α (TNFα) on toxicity. Finally, we investigated the effect of cathinone breakdown products using ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry and studied their involvement in toxicity. We observed dose-dependent increases in cytotoxicity and decreases in mitochondrial respiration following treatment with all cathinones and amphetamines. Glutathione depletion increases amphetamine, but not cathinone toxicity. Bcl-2 and TNFα pathways are involved in toxicity but dopamine levels are not. We also show that cathinones, but not amphetamines, spontaneously produce reactive species and cytotoxic methylbenzamide breakdown products when in aqueous solution. These results provide an important first insight into the mechanisms of cathinone cytotoxicity and pave the way for further studies on cathinone toxicity in vivo. PMID:26462443

  12. Structure-activity relationship of CART peptide fragments

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Maixnerová, Jana; Hlaváček, Jan; Blokešová, Darja; Elbert, Tomáš; Šanda, Miloslav; Slaninová, Jiřina; Železná, Blanka

    2007-01-01

    Roč. 88, č. 4 (2007), s. 565. ISSN 0006-3525. [American Peptide Society Symposium /20./. 26.06.2007-30.06.2007, Montreal] Institutional research plan: CEZ:AV0Z40550506 Keywords : cocaine and amphetamine regulated transcript peptide * structure * activity Subject RIV: CE - Biochemistry

  13. Anorexigenní neuropeptid CART v regulaci příjmu potravy

    Czech Academy of Sciences Publication Activity Database

    Nagelová, Veronika; Železná, Blanka; Maletínská, Lenka

    2014-01-01

    Roč. 108, č. 4 (2014), s. 354-357. ISSN 0009-2770 R&D Projects: GA ČR GAP303/10/1368 Institutional support: RVO:61388963 Keywords : CART * cocaine and amphetamine regulated transcript * anorexigenic neuropeptide Subject RIV: CE - Biochemistry Impact factor: 0.272, year: 2014

  14. Diet-induced and monosodium-glutamate obesity in mice: Relationship among neuropeptide Y, CART peptide and cholecystokinin in feeding behavior

    Czech Academy of Sciences Publication Activity Database

    Železná, Blanka; Matyšková, Resha; Maixnerová, Jana; Haugvicová, Renata; Blokešová, Darja; Maletínská, Lenka

    2007-01-01

    Roč. 88, č. 4 (2007), s. 557. ISSN 0006-3525. [American Peptide Society Symposium /20./. 26.06.2007-30.06.2007, Montreal] Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510 Keywords : cocaine and amphetamine regulated transcript peptide * cholecystokinin Subject RIV: CE - Biochemistry

  15. Effects of psychostimulants on social interaction in adult male rats

    Czech Academy of Sciences Publication Activity Database

    Šlamberová, R.; Mikulecká, Anna; Macúchová, E.; Hrebíčková, I.; Ševčíková, M.; Nohejlová, K.; Pometlová, M.

    2015-01-01

    Roč. 26, č. 8 (2015), s. 776-785. ISSN 0955-8810 Institutional support: RVO:67985823 Keywords : amphetamine * cocaine * male rats * 3,4 methylenedimethoxyamphetamine * psychostimulants * social behavior Subject RIV: FH - Neurology Impact factor: 2.148, year: 2014

  16. A Prospective Study of Stimulant Response in Preschool Children: Insights from ROC Analyses

    Science.gov (United States)

    Short, Elizabeth J.; Manos, Michael J.; Findling, Robert L.; Schubel, Emily A.

    2004-01-01

    Objective: The purpose of this study was to examine the efficacy of psychostimulant medication in a naturalistic sample of preschoolers. Benefits and side effects for methylphenidate and mixed amphetamine salts (Adderall) were examined. Method: Twenty-eight preschoolers (ages 4.0-5.9) participated in the present investigation. They were obtained…

  17. Effects of long acting methylphenidate on ghrelin levels in male children with attention deficit hyperactivity disorder: an open label trial

    Directory of Open Access Journals (Sweden)

    ozhan yalcin

    2014-01-01

    Conclusion: This is the first study which directly aims to determine methylphenidate’s effect on serum active ghrelin levels. Further research with higher methylphenidate doses and/or other stimulants such as atomoxetine and amphetamine should be done as ghrelin is also associated with obesity, alcohol and drug addiction and reward system pathologies, which are also closely related to attention deficit hyperactivity disorder.

  18. Performance Enhancement at the Cost of Potential Brain Plasticity: Neural Ramifications of Nootropic Drugs in the Healthy Developing Brain

    OpenAIRE

    Urban, Kimberly R.; Wen-Jun eGao

    2014-01-01

    Cognitive enhancement is perhaps one of the most intriguing and controversial topics in neuroscience today. Currently, the main classes of drugs used as potential cognitive enhancers include psychostimulants (methylphenidate, amphetamine), but wakefulness-promoting agents (modafinil) and glutamate activators (ampakine) are also frequently used. Pharmacologically, substances that enhance the components of the memory/learning circuits - dopamine, glutamate (neuronal excitation), and/or norepine...

  19. Patterns, Trends, and Meanings of Drug Use by Dance-Drug Users in Edinburgh, Scotland

    Science.gov (United States)

    Riley, Sarah C. E.; Hayward, Emma

    2004-01-01

    A survey of drug use in the past year was completed by 124 clubbers (50% male, 50% female, age range 14-44, mean 24 years). Participants were self selecting and recruited in clubs and pre-club bars. Prevalence rates for alcohol, cannabis, and ecstasy were over 80%; 63% reported cocaine and 53% amphetamine use, 15%-43% used ketamine, psilocybin,…

  20. DEA Multi-Media Drug Library

    Science.gov (United States)

    ... News Releases Speeches and Testimony Major Operations Multi-Media Library Micrograms Legislative & Legal Resources Events ESPAÑOL Contáctenos ... DEA Liderazgo de la DEA Press Room » Multi-Media Library IMAGE GALLERY Drug Photos Amphetamines/Stimulants K2/ ...

  1. Performance-Enhancing Drugs in Sports: How Chemists Catch Users

    Science.gov (United States)

    Werner, T. C.; Hatton, Caroline K.

    2011-01-01

    The "cat-and-mouse game" between those who enable athletes to use performance-enhancing drugs (PEDs) and those who try to detect such use provides a wealth of interesting examples for the undergraduate chemistry and biochemistry classroom. In this article, we focus on several commonly used PEDs, including amphetamine, anabolic steroids,…

  2. Improving General Intelligence with a Nutrient-Based Pharmacological Intervention

    Science.gov (United States)

    Stough, Con; Camfield, David; Kure, Christina; Tarasuik, Joanne; Downey, Luke; Lloyd, Jenny; Zangara, Andrea; Scholey, Andrew; Reynolds, Josh

    2011-01-01

    Cognitive enhancing substances such as amphetamine and modafinil have become popular in recent years to improve acute cognitive performance particularly in environments in which enhanced cognition or intelligence is required. Nutraceutical nootropics, which are natural substances that have the ability to bring about acute or chronic changes in…

  3. 77 FR 2778 - Sentencing Guidelines for United States Courts

    Science.gov (United States)

    2012-01-19

    ... difference in relative potency? The Drug Enforcement Administration has described BZP as a stimulant that is 10 to 20 times less potent than amphetamine. See 75 FR 47451 (August 6, 2010) (``BZP is about 20... inserting ``Notes''; by redesignating Note 1 as Note 3; in that Note, by striking ``Section 3B1.3 (Abuse...

  4. Utah Drop-Out Drug Use Questionnaire.

    Science.gov (United States)

    Governor's Citizen Advisory Committee on Drugs, Salt Lake City, UT.

    This questionnaire assesses drug use practices in high school drop-outs. The 79 items (multiple choice or apply/not apply) are concerned with demographic data and use, use history, reasons for use/nonuse, attitudes toward drugs, availability of drugs, and drug information with respect to narcotics, amphetamines, LSD, Marijuana, and barbiturates.…

  5. A Comparative Study of the Attitudes of College Students and Drug Treatment Center Residents Toward Drugs, Other Drug Users and Themselves.

    Science.gov (United States)

    Page, Richard C.; Mitchell, Sam

    1986-01-01

    Assessed the attitudes of college students and drug treatment center residents with histories of using marijuana and amphetamines. The drug treatment center residents tended to devalue themselves, drugs, and peers in the drug culture to a greater extent than the students. (Author/BL)

  6. Long-Term Effects of Adderall XR in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-06-01

    Full Text Available The long-term tolerability and effectiveness of extended release mixed amphetamine salts (Adderall XR in children with attention deficit hyperactivity disorder (ADHD were evaluated in a 24-month, multicenter, open-label extension of 2 placebo-controlled studies at UCLA, Massachusetts General Hospital, UC-Irvine, Maitland, FL, and Shire Pharmaceutical, Wayne, PA.

  7. Fenethylline (Captagon) Abuse - Local Problems from an Old Drug Become Universal.

    Science.gov (United States)

    Katselou, Maria; Papoutsis, Ioannis; Nikolaou, Panagiota; Qammaz, Samir; Spiliopoulou, Chara; Athanaselis, Sotiris

    2016-08-01

    Fenethylline is a theophylline derivative of amphetamine having stimulant effects similar to those of other amphetamine-type derivatives. Fenethylline was used as medicament for hyperactivity disorders in children, narcolepsy and depression, but it has also been used as a drug of abuse under the common name of 'captagon'. Unlike other drugs of abuse, the clandestine synthesis of fenethylline is simple, using inexpensive laboratory instrumentation and raw materials legal to obtain. A review of all the existing knowledge of fenethylline is reported, concerning its chemistry, synthesis, pharmacology and toxicology, legislation, its prevalence and use as drug of abuse, as well as its analysis in biological or seized samples. Published or reported captagon-related cases and seizures are also presented. All the reviewed information was gathered through a detailed search of PubMed and the Internet. The primary drug market for fenethylline (as captagon) has traditionally been countries located on the Arabian Peninsula but also North Africa since 2013. In Arab countries, millions of captagon tablets are seized every year which represents one-third of global amphetamines seizures within a year. Furthermore, three of four patients treated for drug problems in Saudi Arabia are addicted to amphetamines, almost exclusively in the form of captagon. Significant information on fenethylline is provided for pharmacologists, toxicologists and forensic pathologists. Fenethylline, although old, has recently been introduced to the drug market, especially in Arab countries. Continuous community alertness is needed to tackle this current growing phenomenon. PMID:27004621

  8. 76 FR 30970 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-05-27

    ... January 18, 2011, and published in the Federal Register on February 2, 2011, 76 FR 5829, AMRI Rensselaer... controlled substances: Drug Schedule Marihuana (7360) I Tetrahydrocannabinols (7370) I Amphetamine (1100) II... distribution to its customers. In reference to drug code 7360 (Marihuana), the company plans to...

  9. Boron in nuclear medicine: New synthetic approaches to PET and SPECT

    International Nuclear Information System (INIS)

    This annual progress report describes new methods of incorporation of radioiodine into physiologically active compounds (amphetamines), and the use of organoboranes to labeled radiopharmaceuticals with Oxygen- 15, Nitrogen-13, carbon-11 and fluorine-18. Preclinical studies are also reported on evaluation of butyothiophenones as agents acting at dopaminergic or serotonic synapses

  10. Stimulants and Cardiovascular Events in Youth with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Olfson, Mark; Huang, Cecilia; Gerhard, Tobias; Winterstein, Almut G.; Crystal, Stephen; Allison, Paul D.; Marcus, Steven C.

    2012-01-01

    Objective: This study examined associations between stimulant use and risk of cardiovascular events and symptoms in youth with attention-deficit/hyperactivity disorder and compared the risks associated with methylphenidate and amphetamines. Method: Claims were reviewed of privately insured young people 6 to 21 years old without known…

  11. DEA Multi-Media Drug Library

    Science.gov (United States)

    ... Releases Speeches and Testimony Major Operations Multi-Media Library Micrograms Legislative & Legal Resources Events ESPAÑOL Contáctenos Declaración ... Liderazgo de la DEA Press Room » Multi-Media Library IMAGE GALLERY Drug Photos Amphetamines/Stimulants K2/Spice ...

  12. Modulation of mGlu2 Receptors, but Not PDE10A Inhibition Normalizes Pharmacologically-Induced Deviance in Auditory Evoked Potentials and Oscillations in Conscious Rats.

    Science.gov (United States)

    Ahnaou, Abdallah; Biermans, Ria; Drinkenburg, Wilhelmus H

    2016-01-01

    Improvement of cognitive impairments represents a high medical need in the development of new antipsychotics. Aberrant EEG gamma oscillations and reductions in the P1/N1 complex peak amplitude of the auditory evoked potential (AEP) are neurophysiological biomarkers for schizophrenia that indicate disruption in sensory information processing. Inhibition of phosphodiesterase (i.e. PDE10A) and activation of metabotropic glutamate receptor (mGluR2) signaling are believed to provide antipsychotic efficacy in schizophrenia, but it is unclear whether this occurs with cognition-enhancing potential. The present study used the auditory paired click paradigm in passive awake Sprague Dawley rats to 1) model disruption of AEP waveforms and oscillations as observed in schizophrenia by peripheral administration of amphetamine and the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP); 2) confirm the potential of the antipsychotics risperidone and olanzapine to attenuate these disruptions; 3) evaluate the potential of mGluR2 agonist LY404039 and PDE10 inhibitor PQ-10 to improve AEP deficits in both the amphetamine and PCP models. PCP and amphetamine disrupted auditory information processing to the first click, associated with suppression of the P1/N1 complex peak amplitude, and increased cortical gamma oscillations. Risperidone and olanzapine normalized PCP and amphetamine-induced abnormalities in AEP waveforms and aberrant gamma/alpha oscillations, respectively. LY404039 increased P1/N1 complex peak amplitudes and potently attenuated the disruptive effects of both PCP and amphetamine on AEPs amplitudes and oscillations. However, PQ-10 failed to show such effect in either models. These outcomes indicate that modulation of the mGluR2 results in effective restoration of abnormalities in AEP components in two widely used animal models of psychosis, whereas PDE10A inhibition does not. PMID:26808689

  13. Cerebral emission computer tomography with a rotating gamma camera: clinic results with J-123 Isopropylamphetamin and J-123-Fenetyllin

    International Nuclear Information System (INIS)

    Many amines can pass the blood brain barrier and accumulate in relatively large amounts in the brain tissue. For about 2 years 123-J amphetamines have, therefore, been used for brain imaging by several teams. Our experience sofar is based on 28 patients. Of these, 14 were epileptics, 10 had cerebrovascular diseases, 2 suffered from migraine and another 2 had brain tumors. In 3 patients with vascular lesions studies were repeated twice or three times. Amphetamine uptake in the brain was measured with a rotating gamma camera system (Gammatome T9000/CGR). At an examination time of 20 minutes 64 frames were acquired during one full rotation. The pulse rate was about 3000 second after injecting 6.5 mCi of 123-J amphetamine. Of the epileptics, 8 showed defects both on CT and SPECT, in 3 cases both studies were normal. While 1 patient with CT positivity had a normal SPECT, 2 cases were found to have lesions on SPECT inspite of a normal CT. The size of the lesion seen on amphetamine SPECT was lager than on CT in 3 of 9 patients. In the 10 patients with cerebrovascular lesions the 2 procedures showed concordant normal patterns in 1 and concordant abnormal patterns in 7 instances. 2 patients with normal CT were found to have a lesion on amphetamine scanning which corresponded to the neurologic findings. Regarding the size of the lesions, SPECT showed a more extensive involvement than CT in 2 cases. This again was in good agreement with the neurologic findings. Inspite of repeat studies cerebellar diaschisis was only seen in a single case with healed cerebral infarction and hemiplegia of some years' standing. Two patients suffered from migraine and compromised blood flow was identified as suggested by the neurologic findings inspite of a normal CT. (Author)

  14. Low Impulsive Action, but not Impulsive Choice, Predicts Greater Conditioned Reinforcer Salience and Augmented Nucleus Accumbens Dopamine Release.

    Science.gov (United States)

    Zeeb, Fiona D; Soko, Ashlie D; Ji, Xiaodong; Fletcher, Paul J

    2016-07-01

    Poor impulse control is associated with an increased propensity to develop an addiction and may contribute to relapse as high impulsive subjects appear to attribute greater salience toward drug-paired stimuli. In these studies, we determined whether trait impulsivity also predicts the desire to obtain natural reward-paired stimuli. Rats trained on the 5-choice serial reaction time task to measure impulsive action (Experiment 1) or a delay-discounting task to measure impulsive choice (Experiment 2) were separated into low, intermediate, or high impulsive action (L-IA, I-IA, H-IA) or choice (L-IC, I-IC, H-IC) groups. The motivation to obtain a conditioned stimulus (CS) paired with water-reward was subsequently determined by measuring responding for the CS as a conditioned reinforcer (CRf). Dopamine release in the nucleus accumbens was also measured using in vivo microdialysis. The effects of amphetamine were assessed on all tests. In Experiment 1, amphetamine increased impulsive action in all groups. L-IA rats initially demonstrated the highest responding for the CRf. Amphetamine increased responding for the CRf and this effect was augmented in L-IA rats. Dopamine release following amphetamine was greatest in L-IA subjects. In Experiment 2, amphetamine increased impulsive choice for L-IC and I-IC rats. However, all groups responded similarly for the CRf and dopamine release was moderately greater in L-IC rats. In conclusion, impulsive choice was unrelated to responding for a CRf. L-IA subjects initially attributed enhanced salience to a CS and exhibited greater dopamine release. Lower dopamine release in H-IA rats could result in reduced reinforcing properties of the CRf. PMID:26781518

  15. LC-MS-MS Method for Stimulants in Wastewater During Football Games.

    Science.gov (United States)

    Gul, Waseem; Stamper, Brandon J; Godfrey, Murrell; ElSohly, Mahmoud A

    2016-03-01

    A method was developed for the analysis of amphetamines and cocaine (Coc) in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Seven stimulant-type drugs and metabolites were analyzed. These drugs included amphetamine (Amp), methamphetamine (Meth), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), Coc and benzoylecgonine (BE, the major metabolite of Coc). These drugs were chosen because of their widespread use. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS. Samples were collected on weekends in which the Ole Miss Rebel football team held home games (Vaught-Hemingway Stadium, University, MS 38677). The collected samples were analyzed using a validated method and found to contain Amp, Meth, MDMA, Coc and BE. The concentrations of Amp and BE significantly rose in the university wastewater during football games. PMID:26538543

  16. Drug-related death in Denmark in 2007

    DEFF Research Database (Denmark)

    Simonsen, K. W.; Hansen, A. C.; Rollmann, D.;

    2011-01-01

    INTRODUCTION: We investigated fatal poisonings among drug addicts in 2007. The cause of death, abuse pattern and geographic differences are presented. MATERIAL AND METHODS: All drug-related deaths examined at the three forensic medicine institutes in Denmark in 2007 were evaluated. RESULTS: The...... number of drug-related deaths in 2007 was 226. Methadone deaths had increased since 1997 while heroin/morphine deaths decreased. In earlier studies, very few deaths from central stimulants like cocaine and amphetamines occurred (1-1.5%), but in 2007 6% of the deaths were caused by these drugs. Multiple...... most frequent cause of fatal poisoning and there was a continuous decrease in heroin/morphine deaths. Fatal deaths from cocaine and amphetamine have increased considerably. Multiple drug use was common....

  17. Neurophysiological responses to stressful motion and anti-motion sickness drugs as mediated by the limbic system

    Science.gov (United States)

    Kohl, R. L.; Odell, S.

    1982-01-01

    Performance is characterized in terms of attention and memory, categorizing extrinsic mechanism mediated by ACTH, norepinephrine and dopamine, and intrinsic mechanisms as cholinergic. The cholinergic role in memory and performance was viewed from within the limbic system and related to volitional influences of frontal cortical afferents and behavioral responses of hypothalamic and reticular system efferents. The inhibitory influence of the hippocampus on the autonomic and hormonal responses mediated through the hypothalamus, pituitary, and brain stem are correlated with the actions of such anti-motion sickness drugs as scopolamine and amphetamine. These drugs appear to exert their effects on motion sickness symptomatology through diverse though synergistic neurochemical mechanisms involving the septohippocampal pathway and other limbic system structures. The particular impact of the limbic system on an animal's behavioral and hormonal responses to stress is influenced by ACTH, cortisol, scopolamine, and amphetamine.

  18. Stimulant drug effects on touchscreen automated paired-associates learning (PAL) in rats.

    Science.gov (United States)

    Roschlau, Corinna; Votteler, Angeline; Hauber, Wolfgang

    2016-08-01

    Here we tested in rats effects of the procognitive drugs modafinil and methylphenidate on post-acquisition performance in an object-location paired-associates learning (PAL) task. Modafinil (32; 64 mg/kg) was without effect, while higher (9 mg/kg) but not lower (4.5 mg/kg) doses of methylphenidate impaired PAL performance. Likewise, higher but not lower doses of amphetamine (0.4; 0.8 mg/kg) and MK-801 (0.08; 0.12 mg/kg) decreased PAL performance. Impaired PAL performance induced by methylphenidate, amphetamine, and MK801 most likely reflects compromised cognitive function, e.g., retrieval of learned paired associates. Our data suggest that stimulant drugs such as methylphenidate and modafinil might not facilitate performance in hippocampus-related cognitive tasks. PMID:27421894

  19. Pharmacological characterisation of a modified social interaction model of anxiety in the rat.

    Science.gov (United States)

    Guy, A P; Gardner, C R

    1985-01-01

    Social interaction (SI) between two unfamiliar male rats in a dimly lit, familiar environment has been investigated as a model of anxiety, where novelty of the partner remains as the principal anxiogenic stimulus. A range of centrally acting drugs have been tested in this situation. Chlordiazepoxide, nitrazepam, flunitrazepam, and flurazepam all increase SI, as does buspirone, CL 218872, suriclone, sodium valproate, and nicotinamide in the model described. Anxiogenic agents FG 7142 and yohimbine reduced SI without significant modification of motor activities. However, the stimulant amphetamine increased all behaviours in this condition. Amphetamine also increased all behaviours when rats were tested with their cagemates, when the desire for SI is largely satiated. CL 218872 also increased SI in this second situation, and it is suggested that this agent may have a non-specific component in its action in this test. Additionally, caffeine, theophylline, and piracetam may also have non-specific behavioural actions in this model. PMID:2864655

  20. Quantitative analysis of abused drugs in physiological fluids by gas chromatography/chemical ionization mass spectrometry

    International Nuclear Information System (INIS)

    Methods have been developed for quantitative analysis of commonly abused drugs in physiological fluids using gas chromatography/chemical ionization mass spectrometry. The methods are being evaluated in volunteer analytical and toxicological laboratories, and analytical manuals describing the methods are being prepared. The specific drug and metabolites included in this program are: Δ9-tetrahydrocannabinol, methadone, phencyclidine, methaqualone, morphine, amphetamine, methamphetamine, mescaline, 2,5-dimethoxy-4-methyl amphetamine, cocaine, benzoylecgonine, diazepam, and N-desmethyldiazepam. The current analytical methods utilize relatively conventional instrumentation and procedures, and are capable of measuring drug concentrations as low as 1 ng/ml. Various newer techniques such as sample clean-up by high performance liquid chromatography, separation by glass capillary chromatography, and ionization by negative ion chemical ionization are being investigated with respect to their potential for achieving higher sensitivity and specificity, as well as their ability to facilitate simultaneous analysis of more than one drug and metabolite. (Auth.)

  1. The effects of extreme nutritional conditions on the neurochemistry of reward and addiction

    Science.gov (United States)

    Pothos, Emmanuel N.

    2001-08-01

    Weight loss is a frequent problem in space flights. We now claim that it may affect performance and drug-seeking behavior by altering midbrain neurochemistry. In food-deprived rats (20-30% underweight) basal extracellular dopamine levels in the nucleus accumbens decrease to 40-50% of normal and locomotion is depressed. However, amphetamine-induced dopamine release and locomotion are higher than in controls (1825% vs. 595% after a 25 μM d-amphetamine intraaccumbens infusion). The lower basal and the higher stimulated dopamine levels suggest that the neurotransmitter accumulates presynaptically in the accumbens of the underweight rats due to subnormal basal release. Psychostimulants are more rewarding for underweight subjects possibly because they release significantly more dopamine from elevated presynaptic stores into the accumbens. Consequently, weight loss can lead both to depression of performance and propensity to substance abuse. These effects should be considered when providing nutritional resources for space flights so that weight loss is limited.

  2. Midkine and Pleiotrophin in the Treatment of Neurodegenerative Diseases and Drug Addiction.

    Science.gov (United States)

    Alguacil, Luis F; Herradón, Gonzalo

    2015-01-01

    Pleiotrophin (PTN) and Midkine (MK) are neurotrophines with documented protective actions in experimental models of neurodegenerative diseases and beneficial effects on toxicity and addictive behaviours related to drug abuse. Concerning the latter, both PTN and MK prevent the neurotoxic effects of amphetamine on nigrostriatal pathways and endogenous PTN also limits amphetamine reward. Moreover, endogenous PTN overexpression in the prefontral cortex abolishes alcohol- induced conditioned place preference. This review summarizes the existing patents for using PTN and MK in the treatment and diagnosis of neuropsychiatric disorders with a focus on neurotoxicity, neurodegeneration and substance use disorders. We have also reviewed the mechanism of action of PTN and MK and summarized existing patents on downstream modulators in their signaling pathways for the same indications. PMID:25808239

  3. Illicit drugs in wastewater of the city of Zagreb (Croatia)--estimation of drug abuse in a transition country.

    Science.gov (United States)

    Terzic, Senka; Senta, Ivan; Ahel, Marijan

    2010-08-01

    A comprehensive study of various psychoactive substances and their metabolites was performed in the wastewater treatment plant of the city of Zagreb (780 000 inhabitants) using liquid chromatography/tandem mass spectrometry (LC-MS-MS). The estimation of drug abuse for five different illicit drugs, including heroin, cocaine, marijuana, amphetamine and ecstasy, was made on the basis of their representative excretion rates, which were determined over a period of 8 months. Marijuana (1000 kg/year), heroin (75 kg/year) and cocaine (47 kg/year) were found to be the most frequently consumed illicit drugs, while the consumption of amphetamine-type drugs was much lower (1-3 kg/year). A comparison with other reports indicated that drug abuse profiles in transition countries might be different from those reported for Western Europe, in particular with respect to the comparatively increased consumption of heroin. Enhanced consumption of stimulating drugs (cocaine and ectasy) was systematically detected during weekends. PMID:20510491

  4. Alternative pharmacological strategies for adult ADHD treatment: a systematic review.

    Science.gov (United States)

    Buoli, Massimiliano; Serati, Marta; Cahn, Wiepke

    2016-01-01

    Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder. PMID:26693882

  5. Tolerance to the locomotor-activating effects of 3,4-methylenedioxymethamphetamine (MDMA) predicts escalation of MDMA self-administration and cue-induced reinstatement of MDMA seeking in rats

    OpenAIRE

    Ball, Kevin T.; Slane, Mylissa

    2014-01-01

    Pre-clinical studies of individual differences in addiction vulnerability have been increasing over recent years, but the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) has received relatively little attention in this regard. Previously, we reported large individual differences both in rats' initial behavioral response to experimenter-administered MDMA and their degree of behavioral sensitization to repeated administration. To determine whether these differences coul...

  6. ‘Ecstasy’ Enhances Noise-Induced Hearing Loss

    OpenAIRE

    Church, Michael W.; Zhang, Jinsheng S.; Langford, Megan M.; Perrine, Shane A.

    2013-01-01

    ‘Ecstasy’ or 3,4-methylenedioxy-N-methamphetamine (MDMA) is an amphetamine abused for its euphoric, empathogenic, hallucinatory, and stimulant effects. It is also used to treat certain psychiatric disorders. Common settings for Ecstasy use are nightclubs and “rave” parties where participants consume MDMA and dance to loud music. One concern with the club setting is that exposure to loud sounds can cause permanent sensorineural hearing loss. Another concern is that consumption of MDMA may enha...

  7. Endocrine and Neurochemical Effects of 3,4-Methylenedioxymethamphetamine and Its Stereoisomers in Rhesus Monkeys

    OpenAIRE

    Murnane, K.S.; Fantegrossi, W. E.; Godfrey, J. R.; Banks, M L; Howell, L L

    2010-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that elicits complex biological effects in humans. One plausible mechanism for this phenomenon is that racemic MDMA is composed of two stereoisomers that exhibit qualitatively different pharmacological effects. In support of this, studies have shown that R(−)-MDMA tends to have hallucinogen-like effects, whereas S(+)-MDMA tends to have psychomotor stimulant-like effects. However, relatively little is known about whether the...

  8. Discriminative Stimulus Effects of Psychostimulants and Hallucinogens in S(+)-3,4-Methylenedioxymethamphetamine (MDMA) and R(−)-MDMA Trained Mice

    OpenAIRE

    Murnane, K.S.; Murai, N.; Howell, L L; Fantegrossi, W. E.

    2009-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is a substituted phenethylamine more commonly known as the drug of abuse “ecstasy.” The acute and persistent neurochemical effects of MDMA in the mice are distinct from those in other species. MDMA shares biological effects with both amphetamine-type stimulants and mescaline-type hallucinogens, which may be attributable to distinct effects of its two enantiomers, both of which are active in vivo. In this regard, among the substituted phenethylamines, R...

  9. ACTIONS OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA) ON CEREBRAL DOPAMINERIC, SEROTONERGIC AND CHOLINERGIC NEURONS

    OpenAIRE

    Gudelsky, Gary A.; Yamamoto, Bryan K.

    2007-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative and a popular drug of abuse that exhibits mild hallucinogenic and rewarding properties and engenders feelings of connectedness and openness. The unique psychopharmacological profile of this drug of abuse most likely is derived from the property of MDMA to promote the release of dopamine and serotonin (5-HT) in multiple brain regions. The present review highlights primarily data from studies employing in vivo microdialysis t...

  10. Effects of Stress and MDMA on Hippocampal Gene Expression

    OpenAIRE

    Weber, Georg F.; Johnson, Bethann N.; Yamamoto, Bryan K.; Gudelsky, Gary A.

    2014-01-01

    MDMA (3,4-methylenedioxymethamphetamine) is a substituted amphetamine and popular drug of abuse. Its mood-enhancing short-term effects may prompt its consumption under stress. Clinical studies indicate that MDMA treatment may mitigate the symptoms of stress disorders such as posttraumatic stress syndrome (PTSD). On the other hand, repeated administration of MDMA results in persistent deficits in markers of serotonergic (5-HT) nerve terminals that have been viewed as indicative of 5-HT neuro...

  11. The role of norephinephrine in the pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy")

    OpenAIRE

    Hysek, Cédric Marc

    2013-01-01

    The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a widely used recreational drug, which produces strong psychological effects such as increased empathy and sociability. MDMA inhibits the uptake of and releases serotonin, dopamine, and norepinephrine via an interaction with the respective monoamine transporter. While the role of serotonin in the human pharmacology of MDMA has been well described, the role of norepinephrine in the mediation of the effect of MDMA i...

  12. Methylphenidate for attention deficit hyperactivity disorder and drug relapse in criminal offenders with substance dependence : a 24-week randomized placebo-controlled trial.

    OpenAIRE

    Konstenius, Maija; Jayaram-Lindström, Nitya; Guterstam, Joar; Beck, Olof; Philips, Björn; Franck, Johan

    2014-01-01

    AIM: To test the efficacy and safety of osmotic release oral system (OROS) methylphenidate (MPH) in doses up to 180 mg/day to treat attention deficit hyperactivity disorder (ADHD) and prevent any drug relapse in individuals with a co-diagnosis of ADHD and amphetamine dependence. DESIGN: Randomized placebo-controlled 24-week double-blind trial with parallel groups design. SETTING: Participants were recruited from medium security prisons in Sweden. The medication started within 2 weeks before r...

  13. Phenylpropanolamine and cerebral hemorrhage

    International Nuclear Information System (INIS)

    Computerized tomography, carotid angiograms, and arteriography were used to diagnose several cases of cerebral hemorrhage following the use of phenylpropanolamine. The angiographic picture in one of the three cases was similar to that previously described in association with amphetamine abuse and pseudoephedrine overdose, both substances being chemically and pharmacologically similar to phenylpropanolamine. The study suggests that the arterial change responsible for symptoms may be due to spasm rather than arteriopathy. 14 references, 5 figures

  14. Distinctive Personality Traits and Neural Correlates Associated with Stimulant Drug Use Versus Familial Risk of Stimulant Dependence

    OpenAIRE

    Ersche, Karen D.; Jones, P. Simon; Williams, Guy B.; Smith, Dana G.; Bullmore, Edward T.; Robbins, Trevor W.

    2013-01-01

    Background Stimulant drugs such as cocaine and amphetamine have a high abuse liability, but not everyone who uses them develops dependence. However, the risk for dependence is increased for individuals with a family history of addiction. We hypothesized that individuals without a family history of dependence who have been using cocaine recreationally for several years but have not made the transition to dependence will differ in terms of personality traits and brain structure from individuals...

  15. Prevalence and risk of injury in Europe by driving with alcohol, illicit drugs and medicines.

    OpenAIRE

    Bernhoft, I.M. Hels, T. Lyckegaard, A. Houwing, S. & Verstraete, A.G.

    2012-01-01

    Prevalence and injury risk of driving with alcohol, illicit drugs and medicines have been estimated as part of the DRUID (Driving under the Influence of Drugs, Alcohol and Medicines) project of FP6. Prevalence in the driving population was based on roadside surveys in thirteen European countries, prevalence in seriously injured drivers and killed drivers on data from nine countries. Blood and/or saliva samples were collected and analysed for ethanol, amphetamines, cocaine, cannabis, illicit o...

  16. Seizures After Overdoses of Bupropion Intake

    OpenAIRE

    Kara, Hasan; AK, Ahmet; Bayır, Ayşegül; Acar, Demet; İstanbulluoğlu, Rabia; Değirmenci, Selim

    2013-01-01

    Background: Bupropion is a new-generation monocyclic antidepressant that has been accidentally found to have potential effects on reducing nicotine addiction. It is structurally similar to stimulants such as amphetamine and inhibits dopamine and noradrenalin reuptake selectively. Case Reports: We report two cases with no history of epilepsy who took oral bupropion for depression and had generalised tonic-clonic type of seizures in their follow-ups. Conclusion: After an ov...

  17. Bupropion improves attention but does not affect impulsive behavior in healthy young adults

    OpenAIRE

    Acheson, Ashley; de Wit, Harriet

    2008-01-01

    Bupropion is an effective abstinence aid for cessation of smoking and possibly other drug use as well. There is evidence that bupropion improves attention and impulse control in certain patient populations, and improvements in these processes could mediate its efficacy as an abstinence aid. In the present study, we tested the effects of acute bupropion on measures of attention and impulsivity in healthy adults with d-amphetamine included as a positive control. Twenty-two nonsmokers (11 women)...

  18. Asenapine effects in animal models of psychosis and cognitive function

    OpenAIRE

    Hugh M Marston; Young, Jared W.; Martin, Frederic D.; Serpa, Kevin A.; Moore, Christopher L; Wong, Erik H.; Gold, Lisa; Meltzer, Leonard T.; Azar, Marc R.; Geyer, Mark A.; Shahid, Mohammed

    2009-01-01

    Rationale Asenapine, a novel psychopharmacologic agent in the development for schizophrenia and bipolar disorder, has high affinity for serotonergic, α-adrenergic, and dopaminergic receptors, suggesting potential for antipsychotic and cognitive-enhancing properties. Objectives The effects of asenapine in rat models of antipsychotic efficacy and cognition were examined and compared with those of olanzapine and risperidone. Materials and methods Amphetamine-stimulated locomotor activity (Amp-LM...

  19. The Behavioral Actions of Lithium in Rodent Models: Leads to Develop Novel Therapeutics

    OpenAIRE

    O’Donnell, Kelley C.; Gould, Todd D.

    2007-01-01

    For nearly as long as lithium has been in clinical use for the treatment of bipolar disorder, depression, and other conditions, investigators have attempted to characterize its effects on behaviors in rodents. Lithium consistently decreases exploratory activity, rearing, aggression, and amphetamine-induced hyperlocomotion; and it increases the sensitivity to pilocarpine-induced seizures, decreases immobility time in the forced swim test, and attenuates reserpine-induced hypolocomotion. Lithiu...

  20. Glutamate Receptors as Targets of Protein Kinase C in the Pathophysiology and Treatment of Animal Models of Mania

    OpenAIRE

    Szabo, Steven; Machado-Vieira, Rodrigo; Yuan, Peixiong; Wang, Yun; Wei, Yanling; Falke, Cynthia; Cirelli, Chiara; Tononi, Giulio; Manji, Husseini K; Du, Jing

    2008-01-01

    Considerable biochemical evidence suggests that the protein kinase C (PKC) signaling cascade may be a convergent point for the actions of anti-manic agents, and that excessive PKC activation can disrupt prefrontal cortical regulation of thinking and behavior. To date, however, brain protein targets of PKC’s anti-manic effects have not been fully identified. Here we showed that PKC activity was enhanced in the prefrontal cortex of animals treated with the psychostimulant amphetamine. Phosphory...

  1. Cocaine Self-Administration Produces Pharmacodynamic Tolerance: Differential Effects on the Potency of Dopamine Transporter Blockers, Releasers, and Methylphenidate

    OpenAIRE

    Ferris, Mark J.; Calipari, Erin S.; Mateo, Yolanda; Melchior, James R.; Roberts, David CS; JONES, SARA R.

    2012-01-01

    The dopamine transporter (DAT) is the primary site of action for psychostimulant drugs such as cocaine, methylphenidate, and amphetamine. Our previous work demonstrated a reduced ability of cocaine to inhibit the DAT following high-dose cocaine self-administration (SA), corresponding to a reduced ability of cocaine to increase extracellular dopamine. However, this effect had only been demonstrated for cocaine. Thus, the current investigations sought to understand the extent to which cocaine S...

  2. Methylenedioxymethamphetamine (‘Ecstasy’)-induced immunosuppression: a cause for concern?

    OpenAIRE

    Boyle, Noreen T; Connor, Thomas J.

    2010-01-01

    Methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) is a ring-substituted amphetamine and a popular drug of abuse. In addition to ability to induce euphoria, MDMA abuse is associated with a range of acute and long-term hazardous effects. This paper is focused on once such adverse effect: its ability to negatively impact on functioning of the immune system. Research demonstrates that MDMA has immunosuppressive properties, with both innate and adaptive arms of the immune system being affected. The ...

  3. Reinforcement magnitude modulation of rate dependent effects in pigeons and rats.

    Science.gov (United States)

    Ginsburg, Brett C; Pinkston, Jonathan W; Lamb, R J

    2011-08-01

    Response rate can influence the behavioral effects of many drugs. Reinforcement magnitude may also influence drug effects. Further, reinforcement magnitude can influence rate-dependent effects. For example, in an earlier report, we showed that rate-dependent effects of two antidepressants depended on reinforcement magnitude. The ability of reinforcement magnitude to interact with rate-dependency has not been well characterized. It is not known whether our previous results are specific to antidepressants or generalize to other drug classes. Here, we further examine rate-magnitude interactions by studying effects of two stimulants (d-amphetamine [0.32-5.6 mg/kg] and cocaine [0.32-10 mg/kg]) and two sedatives (chlordiazepoxide [1.78-32 mg/kg] and pentobarbital [1.0-17.8 mg/kg]) in pigeons responding under a 3-component multiple fixed-interval (FI) 300-s schedule maintained by 2-, 4-, or 8-s of food access. We also examine the effects of d-amphetamine [0.32-3.2 mg/kg] and pentobarbital [1.8-10 mg/kg] in rats responding under a similar multiple FI300-s schedule maintained by 2- or 10- food pellet (45 mg) delivery. In pigeons, cocaine and, to a lesser extent, chlordiazepoxide exerted rate-dependent effects that were diminished by increasing durations of food access. The relationship was less apparent for pentobarbital, and not present for d-amphetamine. In rats, rate-dependent effects of pentobarbital and d-amphetamine were not modulated by reinforcement magnitude. In conclusion, some drugs appear to exert rate-dependent effect which are diminished when reinforcement magnitude is relatively high. Subsequent analysis of the rate-dependency data suggest the effects of reinforcement magnitude may be due to a diminution of drug-induced increases in low-rate behavior that occurs early in the fixed-interval. PMID:21707192

  4. Minocycline affects cocaine sensitization in mice

    OpenAIRE

    Chen, Hu; Uz, Tolga; Manev, Hari

    2009-01-01

    Growing evidence has pointed to an interaction between the tetracycline antibiotic minocycline and drugs with abuse liability such as opioids and amphetamines. In this work, we tested the hypothesis that similar to its effects on methamphetamine-induced locomotor sensitization, minocycline may influence the behavioral effects of cocaine. Experiments were performed in male C57BL/6J mice using an automated system to measure locomotor activity. We found that 80 mg/kg minocycline significantly re...

  5. Drugs of abuse and human placenta

    OpenAIRE

    Ganapathy, Vadivel

    2010-01-01

    Drugs of abuse such as cocaine and amphetamines, when used by pregnant women, exert deleterious effects on the fetus. These drugs produce their effects through inhibition of the serotonin transporter, norepinephrine transporter, and dopamine transporter. The inhibition can occur in the pregnant mother as well as in the fetus. These events contribute to the detrimental effects of these drugs on the fetus. However, the role of placenta, which serves as the link between the pregnant mother and t...

  6. Natural history, symptoms and treatment of the narcoleptic syndrome.

    Science.gov (United States)

    Parkes, J D; Baraitser, M; Marsden, C D; Asselman, P

    1975-11-01

    This study describes the clinical features, natural history and treatment of 100 patients with narcolepsy. Over half had one or more affected relatives. Symptoms commenced in adolescence or early adult life in most patients, and remissions were uncommon. Narcolepsy occurred several times each day, often in unusual circumstances and sometimes with little warning. The mean total sleep time of narco-leptics was a little over 9 hours in each 24 hour period, as compared with under 8 in normal subjects. Cataplexy occurred in 93 patients, most commonly when subjects were tired. Attacks were similar in nature to physiological weakness with laughter, although other sudden sensory or emotional stimuli did not cause paralysis of voluntary movement nor loss of muscle tone in normal subjects. Half these patients had frequent dreams before the onset of proper sleep, and 62 had sleep paralysis. This was often frightening, with feelings of suffocation, accompanied by dreams, and of uncertain length. A minority of patients with narcolepsy had muscle aches and jerks before sleep, double vision or loss of focus during cataplexy, went sleep-walking by day, and had daytime hallucinations. Amphetamines had been given to 71 patients for periods of up to 33 years with adequate, but rarely complete, control of narcolepsy. Side effects were common and almost half these patients became tolerant, needing higher dosage to control symptoms. Three patients had a cerebrovascular accident whilst taking amphetamines. Imipramine or clomipramine had ben given in combination with amphetamines to 33 patients for periods of up to 6 years with considerable improvement in both cataplexy and sleep paralysis, and few side effects. Sustained or paroxysmal hypertension as a result of amphetamines or combined treatment did not occur. PMID:19899267

  7. Cognitive judgment bias in the psychostimulant-induced model of mania in rats

    OpenAIRE

    Rygula, Rafal; Szczech, Ewa; Kregiel, Jakub; Golebiowska, Joanna; Kubik, Jakub; Popik, Piotr

    2014-01-01

    Rationale Animal models of mania lack genuine cognitive parameters. The present gold standard of mania models, amphetamine-induced hyperlocomotion, is rather unspecific and does not necessarily target its cardinal symptoms. Therefore, alternative behavioral markers that are sensitive to stimulants are required. Objectives In the present study, by combining the psychostimulant-induced model of mania in rodents with the recently developed ambiguous-cue interpretation (ACI) tests, we investigate...

  8. Similarities in the behavior and molecular deficits in the frontal cortex between the neurotensin receptor subtype 1 knockout mice and chronic phencyclidine-treated mice: relevance to schizophrenia

    OpenAIRE

    Li, Zhimin; Boules, Mona; Williams, Katrina; Gordillo, Andres; Li, Shuhua; Richelson, Elliott

    2010-01-01

    Much evidence suggests that targeting the neurotensin (NT) system may provide a novel and promising treatment for schizophrenia. Our recent work shows that: NTS1 knockout (NTS1−/−) mice may provide a potential animal model for studying schizophrenia by investigating the effect of deletion NTS1 receptor on amphetamine-induced hyperactivity and neurochemical changes. The data indicate a hyper-dopaminergic state similar to the excessive striatal DA activity reported in schizophrenia. The present...

  9. Gestational methylazoxymethanol acetate administration: a developmental disruption model of schizophrenia

    OpenAIRE

    Lodge, Daniel J; Grace, Anthony A.

    2009-01-01

    Animal models are critical for the study of psychiatric disorders since they allow the use of invasive methods that cannot be used for ethical reasons in humans. Currently there are three general models of schizophrenia; (i) those produced with acute pharmacological intervention (i.e. MK-801, ketamine, PCP and amphetamine), (ii) genetic models (i.e. mutant DISC-1, D2-R over expression) and (iii) developmental disruption models (i.e. MAM, neonatal ventral hippocampal lesion, isolation rearing,...

  10. Hippocampal dysfunction and disruption of dopamine system regulation in an animal model of schizophrenia

    OpenAIRE

    Lodge, Daniel J; Grace, Anthony A.

    2008-01-01

    Studies into the pathophysiology of schizophrenia have consistently demonstrated a dysfunction of dopamine (DA) system regulation in this disorder. This includes hyper-responsivity to DA agonists, the therapeutic efficacy of DA antagonists, and augmented striatal DA release in response to amphetamine. Nonetheless, there is little evidence for a pathological alteration with the DA system itself in schizophrenia. Instead, it is suggested that the disturbance lies in the manner by which the DA s...

  11. A possible link between sensation-seeking status and positive subjective effects of oxycodone in healthy volunteers

    OpenAIRE

    Zacny, James P.

    2009-01-01

    Sensation seeking is a personality trait that is linked to use and abuse of drugs. Laboratory studies have established that high sensation seekers, as measured by different instruments, are more likely to report abuse liability-related subjective effects from drugs such as nicotine, alcohol, and d-amphetamine than low sensation seekers. One class of drugs that has not been studied to date in this fashion is opioids. Accordingly, a retrospective analysis encompassing five studies that examined...

  12. Drug: D02574 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02574 Drug Atomoxetine hydrochloride (JAN/USAN); Tomoxetine hydrochloride; Stratte...ans 11 Agents affecting central nervous system 117 Psychotropics 1179 Others D02574 Atom...ly acting sympathomimetics N06BA09 Atomoxetine D02574 Atomoxetine hydrochloride (... Disorder Agents, Non- amphetamines Atomoxetine D02574 Atomoxetine hydrochloride (JAN/USAN) Target-based cla...[HSA:6530] [KO:K05035] Atomoxetine [ATC:N06BA09] D02574 Atomoxetine hydrochloride

  13. Trafficking of Dopamine Transporters in Psychostimulant Actions

    OpenAIRE

    Zahniser, Nancy R.; Sorkin, Alexander

    2009-01-01

    Brain dopamine (DA) plays a pivotal role in drug addiction. Since the plasma membrane DA transporter (DAT) is critical for terminating DA neurotransmission, it is important to understand how DATs are regulated and this regulation impacts drug addiction. The number of cell surface DATs is controlled by constitutive and regulated endocytic trafficking. Psychostimulants impact this trafficking. Amphetamines, DAT substrates, cause rapid up-regulation and slower down-regulation of DAT whereas coca...

  14. GABAB receptor as therapeutic target for drug addiction: from baclofen to positive allosteric modulators

    OpenAIRE

    Roberta Agabio; Giancarlo Colombo

    2015-01-01

    The present paper summarizes experimental and clinical data indicating the therapeutic potential of the GABAB receptor agonist, baclofen, in the treatment of alcohol use disorder (AUD) and substance use disorder (SUD). Multiple preclinical studies have demonstrated the ability of baclofen to suppress alcohol drinking (including binge- and relapse-like drinking), oral alcohol self-administration, and intravenous self-administration of cocaine, nicotine, amphetamine, methamphetamine, morphine, ...

  15. Differential development of tolerance to the functional and behavioral effects of repeated baclofen treatment in rats

    OpenAIRE

    Beveridge, T.J.R.; Smith, H. R.; Porrino, L.J.

    2013-01-01

    Baclofen, a gamma-aminobutyric acid (GABA)B receptor agonist, has been used clinically to treat muscle spasticity, rigidity and pain. More recently, interest in the use of baclofen as an addiction medicine has grown, with promising preclinical cocaine and amphetamine data and demonstrated clinical benefit from alcohol and nicotine studies. Few preclinical investigations, however, have utilized chronic dosing of baclofen, which is important given that tolerance can occur to many of its effects...

  16. Effects of Risperidone and Paliperidone Pretreatment on Locomotor Response Following Prenatal Immune Activation

    Science.gov (United States)

    Richtand, Neil M.; Ahlbrand, Rebecca; Horn, Paul; Stanford, Kevin; Bronson, Stefanie L.; McNamara, Robert K.

    2011-01-01

    Aim Limited data are available regarding pharmacological characteristics of effective interventions for psychosis prevention. Enrollment challenges in psychosis prevention trials impede screening diverse interventions for efficacy. Relevant animal models could help circumvent this barrier. We previously described prevention with risperidone of abnormal behavior following neonatal hippocampal lesion. We aimed to extend those findings evaluating risperidone and paliperidone following prenatal immune activation, a developmental model of a schizophrenia risk factor. We evaluated a later developmental time point to determine persistent effects of drug treatment. Methods Pregnant Sprague-Dawley rats were injected with poly I:C or saline on gestational day 14. Offspring of poly I:C and saline treated dams received risperidone (0.45 mg/kg/d), paliperidone (0.05 mg/kg/d), or vehicle from postnatal days 35 to 70. Locomotor responses to novelty, saline injection, and amphetamine (1 and 5 mg/kg) were determined at three months, i.e., 21 days following antipsychotic discontinuation. Results Risperidone and paliperidone had persistent effects on behavioral response to amphetamine (1 mg/kg) at 3 months, ameliorating the impact of prenatal immune activation on offspring of poly I:C-treated dams. Risperidone, but not paliperidone, also exerted persistent effects in offspring of saline-treated dams on locomotor response to saline and amphetamine (5 mg/kg) injection. Conclusions Risperidone and paliperidone pretreatment of poly I:C offspring during peri-pubertal development stabilized response to amphetamine exposure persisting into early adulthood. Prenatal immune activation provides a model for evaluating effects of an environmental risk factor for schizophrenia, and has potential utility for identifying pharmacological approaches to early intervention. PMID:21440257

  17. Agonist Replacement for Stimulant Dependence: A Review of Clinical Research

    OpenAIRE

    Stoops, William W.; Rush, Craig R.

    2013-01-01

    Stimulant use disorders are an unrelenting public health concern worldwide. Agonist replacement therapy is among the most effective strategies for managing substance use disorders including nicotine and opioid dependence. The present paper reviewed clinical data from human laboratory self-administration studies and clinical trials to determine whether agonist replacement therapy is a viable strategy for managing cocaine and/or amphetamine use disorders. The extant literature suggests that ago...

  18. Reporting a Case of Injecting Methylphenidate (Ritalin) Tablets, Intensified Symptoms of Schizoph-renia or Induce Separate Mental Disorder?

    OpenAIRE

    Ghaffarinejad, Alireza; Kheradmand, Ali

    2009-01-01

    Background: Methylphenidate is one of the classic amphetamines which can cause or exacerbate psychotic symptoms in schizophrenia patients. Case Report: In this paper, a young man is presented with injection of methylphenidate tablets with acute cellulitis due to this injection and the related symptoms. In the first hospitalization and after recovery from psychotic disorder due to tablet injections, he was under treatment with anti-psychotics because of other symptoms related to schizophrenia....

  19. Nucleus accumbens lesions modulate the effects of Methylphenidate

    OpenAIRE

    Podet, Adam; Lee, Min J.; Swann, Alan C.; Dafny, Nachum

    2010-01-01

    The psychostimulant methylphenidate (MPD, Ritalin) is the prescribed drug of choice for treatment of ADHD. In recent years, the diagnosis rate of ADHD has increased dramatically, as have the number of MPD prescriptions. Repeated exposure to psychostimulants produces behavioral sensitization in rats, an experimental indicator of a drug’s potential liability. In studies on cocaine and amphetamine, this effect has been reported to involve the nucleus accumbens (NAc), one of the nuclei belonging ...

  20. The Dopamine Transporter Constitutively Internalizes and Recycles in a Protein Kinase C-regulated Manner in Stably Transfected PC12 Cell Lines*

    OpenAIRE

    Loder, Merewyn K; Melikian, Haley E.

    2003-01-01

    The dopamine transporter (DAT) removes dopamine from the extracellular milieu and is potently inhibited by number of psychoactive drugs, including cocaine, amphetamines, and methylphenidate (Ritalin). Multiple lines of evidence demonstrate that protein kinase C (PKC) down-regulates dopamine transport, primarily by redistributing DAT from the plasma membrane to endosomal compartments, although the mechanisms facilitating transporter sequestration are not defined. Here, we demonstrate that DAT ...