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Sample records for repeated amphetamine stimulation

  1. Amphetamines

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Amphetamines KidsHealth > For Teens > Amphetamines A A A What's ... How Can Someone Quit? Avoiding Amphetamines What Are Amphetamines? Amphetamines are stimulants. They speed up functions in ...

  2. Consequences of amygdala kindling and repeated withdrawal from ethanol on amphetamine-induced behaviours.

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    Ripley, Tamzin L; Dunworth, Sarah J; Stephens, David N

    2002-09-01

    It has been shown previously that chronic ethanol treatment in mice leads to accelerated behavioural sensitization to psychomotor stimulants [Manley & Little (1997) J. Pharmacol. Exp. Ther., 281, 1330-1339], whilst repeated experience of ethanol withdrawal sensitizes pathways underlying seizure activity (Becker & Hale (1993) Alcohol Clin. Exp. Res., 17, 94-98]. The aim of the current experiment was to investigate the consequences of repeated withdrawal from ethanol on amphetamine-induced behaviours in the rat and compare this with animals with electrical kindling of the amygdala, a procedure that has been shown to enhance alcohol withdrawal seizures [Pinel et al. (1975) Can. J. Neurol. Sci., 2, 467-475]. For the kindling experiments, electrodes were surgically implanted in the left basolateral amygdala and were stimulated daily at the afterdischarge threshold until a criterion of three consecutive stage 5 seizures was reached. Fully kindled rats showed a marginally significant reduction in sensitivity to the locomotor stimulant effects of acute amphetamine compared with sham and partially kindled rats which had experienced subthreshold stimulation of the amygdala. Sham and partially kindled rats sensitized readily to the locomotor activating effects of amphetamine (0.125 mg/kg) following repeated treatments, but the fully kindled rats did not. Fully kindled rats also failed to show place preference conditioning to amphetamine (0.5 mg/kg). Rats, withdrawn three times from chronic ethanol (liquid-diet), kindled more quickly to PTZ (30 mg/kg, i.p.) than rats with the same overall exposure to ethanol (24 days) followed by a single withdrawal or control animals. However, there was no difference in the locomotor stimulating effects of acute amphetamine (0.25-1 mg/kg, i.p.), the rate of sensitization to amphetamine (0.125 mg/kg, i.p.) or amphetamine induced conditioned place preference (1 mg/kg, i.p.). These observations suggest that, in rats, repeated withdrawal from a

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

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    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

  4. Stimulant ADHD Medications -- Methylphenidate and Amphetamines

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    ... 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 ...

  5. Influence of benzodiazepine tranquilizers on amphetamine-induced locomotor stimulation in mice.

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    Sansone, M

    1980-01-01

    Four benzodiazepine tranquilizers have been tested, alone or in combination with amphetamine, on spontaneous locomotor activity of C57BL/6 mice. Amphetamine-induced locomotor stimulation was enhanced by chlordiazepoxide, diazepam, and medazepam, but not by bromazepam. The results indicate that benzodiazepine derivatives may be somewhat differentiated on the basis of their interactions with amphetamine.

  6. Amphetamine

    Science.gov (United States)

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

  7. Experimental Investigation on Terahertz Spectra of Amphetamine Type Stimulants

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    Sun, Jin-Hai; Shen, Jing-Ling; Liang, Lai-Shun; Xu, Xiao-Yu; Liu, Hai-Bo; Zhang, Cun-Lin

    2005-12-01

    The spectral absorption features of three amphetamine-type stimulants (ATS) belonging to illicit drugs have been studied with terahertz (THz) time-domain spectroscopy (THz-TDS) and the characteristic absorption spectra (fingerprint spectra) are obtained in the range from 0.2 to 2.5 THz. Fingerprint spectra of illicit drugs in terahertz band are bases to detect and to inspect nondestructively illicit drugs with terahertz technique. With fingerprint spectra of illicit drugs and strong penetrability for cloths, paper bags and leathered or plastic luggage terahertz technique would be better than other techniques in illicit drugs detection and inspection. Thus, this work would contribute to the building of corresponding fingerprint spectra database of illicit drugs and provide experimental bases for using of terahertz detection apparatus in drugs nondestructive detection and inspection in the future.

  8. Experimental Investigation on Terahertz Spectra of Amphetamine Type Stimulants

    Institute of Scientific and Technical Information of China (English)

    SUN Jin-Hai; SHEN Jing-Ling; LIANG Lai-Shun; XU Xiao-Yu; LIU Hai-Bo; ZHANG Cun-Lin

    2005-01-01

    @@ The spectral absorption features of three amphetamine-type stimulants (ATS) belonging to illicit drugs have been studied with terahertz (THz) time-domain spectroscopy (THz-TDS) and the characteristic absorption spectra (fingerprint spectra) are obtained in the range from 0.2 to 2.5 THz. Fingerprint spectra of illicit drugs in terahertz band are bases to detect and to inspect nondestructively illicit drugs with terahertz technique. With fingerprint spectra of illicit drugs and strong penetrability for cloths, paper bags and leathered or plastic luggage terahertz technique would be better than other techniques in illicit drugs detection and inspection. Thus, this work would contribute to the building of corresponding fingerprint spectra database of illicit drugs and provide experimental bases for using of terahertz detection apparatus in drugs nondestructive detection and inspection in the future.

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

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    Ellen M. Leslie

    2016-02-01

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

  10. Exposure to Amphetamines Leads to Development of Amphetamine Type Stimulants Associated Cardiomyopathy (ATSAC).

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    Jafari Giv, Mahsa

    2017-01-01

    With rapidly rising prevalence of exposure to Amphetamine Type Stimulants (ATS), novel insights into cardiotoxic effects of this substance are being presented in the literature and remarkably ATS Associated Cardiomyopathy (ATSAC) is emerging as a novel cardiovascular condition with its distinctive pathogenesis, risk factors, clinical features and prognosis. A comprehensive systematic review was performed to explore and analyze the current evidence on the association between ATS exposure and development of cardiomyopathy, biological mechanisms involved in pathogenesis of ATSAC, risk factors, clinical features and course of patients with ATSAC. Several animal studies, case reports, case series and case-control studies support the association between ATS exposure and ATSAC. Oxidative stress, accelerated apoptosis, increased p53 activity, cardiomyocyte necrosis, perfusion defects, fatty acid toxicity, altered gene expression, abnormal cardiac protein synthesis and function in addition to defects in intracellular calcium hemostasis present themselves as likely mechanisms of cardiotoxicity in ATSAC. Majority of patients with ATSAC were found to be male, young and presented late with severe dilated cardiomyopathy. Female ATS users predominantly develop Takotsubo type of ATSAC and in particular its atypical basal variant. Overall, cessation of ATS exposure seems to be associated with some degree of reversibility and recovery in ATSAC sufferers.

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

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    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.

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

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    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.

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

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    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.

  14. Reinforcing, subject-rated, performance and physiological effects of methylphenidate and d-amphetamine in stimulant abusing humans.

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    Stoops, William W; Glaser, Paul E A; Fillmore, Mark T; Rush, Craig R

    2004-12-01

    Methylphenidate has potential for abuse because it produces behavioural effects similar to those observed with other abused stimulants, such as d-amphetamine and cocaine. The aim of this study was to further characterize the abuse potential of oral methylphenidate relative to oral d-amphetamine. Ten drug-abusing volunteers were recruited to participate in this study, which consisted of seven dose conditions: methylphenidate (16, 32 and 48 mg), d-amphetamine (8, 16 and 24 mg) and placebo. The reinforcing effects of these drugs were assessed during a self-administration session (preceded by a sampling session for each condition) with a modified progressive-ratio procedure. Subject-rated, performance and physiological effects were assessed concurrently during both the sampling and self-administration sessions. The intermediate dose of methylphenidate and d-amphetamine increased responding significantly above placebo levels. Both methylphenidate and d-amphetamine produced dose-dependent increases in stimulant-like subject ratings (e.g. Active, Alert, or Energetic and High), but the effects of these drugs were not isomorphic. These findings are consistent with epidemiological data and previous findings from laboratory studies that suggest methylphenidate has at least some abuse potential.

  15. Influence of bleaching on the enantiomeric disposition of amphetamine-type stimulants in hair.

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    Martins, Liliane Ferreira; Yegles, Michel; Thieme, Detlef; Wennig, Robert

    2008-03-21

    The aim of this work was to study the influence of hair bleaching on the enantiomeric ratios of amphetamine-type stimulants (ATS), including amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine and 3,4-methylenedioxyethylamphetamine. Hair specimens from 14 STA users were treated with a commercial bleaching product during 40 min. After alkaline digestion and solid-phase extraction of bleached and non-bleached hair, the STA enantiomers were derivatised with an in-house synthesised chiral reagent, the (2S,4R)-N-heptafluorobutyryl-4-heptafluorobutoyloxy-prolyl chloride. The diastereoisomers were quantified by GC/MS-NCI. The results showed that the concentrations of all enantiomers decreased in bleached hair in comparison with the non-treated hair (median values between 20 and 39%). The enantiomeric ratios of the STA in bleached hair were not significantly different from those determined in non-treated hair. Our findings pointed out that bleaching treatments decrease concentrations of STA in hair without influencing their enantiomeric ratios.

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

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

    2012-06-15

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

  17. Stimulant therapy in the management of ADHD: mixed amphetamine salts (extended release).

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    Faraone, Stephen V

    2007-09-01

    The efficacy of amphetamines in the management of attention-deficit/hyperactivity disorder (ADHD) is well established. However, their value in improving the symptoms of ADHD has been compromised by concerns about compliance, abuse potential and adverse events. An extended-release formulation of mixed amphetamine salts (MAS XR) provided the first long-acting amphetamine formulation, and thus, filled an important gap in available treatments for ADHD. MAS XR has been shown to improve ADHD symptoms in children, adolescents and adults in both short- and long-term studies. The drug is generally well tolerated in clinical trials. Although its safety profile in patients with concomitant cardiovascular conditions in a real-world setting has yet to be fully evaluated, a tolerability study of mixed amphetamine salts in adults with ADHD who were being treated for primary essential hypertension showed that these patients can be safely treated with MAS XR.

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

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    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.

  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. 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.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  2. 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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  4. Stimulating a normal adjustment: misbehavior, amphetamines, and the electroencephalogram at the Bradley Home for children.

    Science.gov (United States)

    Bromley, Elizabeth

    2006-01-01

    This article uses an historical case study to describe the influence of social and contextual factors on the adoption of somatic approaches to children's misbehavior. The child guidance movement and the emergence of medicalized residential treatment facilities for children influenced the theoretical orientations of physicians treating children's behavior disorders in the United States in the 1930s. Charles Bradley and his colleagues at the Bradley Home in Rhode Island defined behavior disorders in social terms but investigated and treated misbehavior with somatic tools. The use of amphetamines and the electroencephalogram reorganized concepts of maladjustment along neurological lines, even as the research relied on the Home's social priorities. Electroencephalographic investigations especially shaped an organic concept of misbehavior. Ultimately, the somatic orientation obscured the central role of local context in Bradley Home physicians' research.

  5. Dampened Amphetamine-Stimulated Behavior and Altered Dopamine Transporter Function in the Absence of Brain GDNF.

    Science.gov (United States)

    Kopra, Jaakko J; Panhelainen, Anne; Af Bjerkén, Sara; Porokuokka, Lauriina L; Varendi, Kärt; Olfat, Soophie; Montonen, Heidi; Piepponen, T Petteri; Saarma, Mart; Andressoo, Jaan-Olle

    2017-02-08

    Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases, including drug addiction and Parkinson's disease. Because of its well established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been studied extensively in various disorders with disturbed dopamine homeostasis. However, the outcomes from preclinical and clinical studies vary, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function. Nevertheless, the current lack of appropriate animal models has limited this understanding. Therefore, we have generated novel mouse models to study conditional Gdnf deletion in the CNS during embryonic development and reduction of striatal GDNF levels in adult mice via AAV-Cre delivery. We found that both of these mice have reduced amphetamine-induced locomotor response and striatal dopamine efflux. Embryonic GDNF deletion in the CNS did not affect striatal dopamine levels or dopamine release, but dopamine reuptake was increased due to increased levels of both total and synaptic membrane-associated dopamine transporters. Collectively, these results suggest that endogenous GDNF plays an important role in regulating the function of dopamine transporters in the striatum.SIGNIFICANCE STATEMENT Delivery of ectopic glial cell line-derived neurotrophic factor (GDNF) promotes the function, plasticity, and survival of midbrain dopaminergic neurons, the dysfunction of which contributes to various neurological and psychiatric diseases. However, how the deletion or reduction of GDNF in the CNS affects the function of dopaminergic neurons has remained unknown. Using conditional Gdnf knock-out mice, we found that endogenous GDNF affects striatal dopamine homeostasis and regulates amphetamine-induced behaviors by regulating the level and function of dopamine transporters. These data regarding the physiological role of GDNF are

  6. 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

  7. 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.

  8. 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

  9. 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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  11. 21 CFR 862.3100 - Amphetamine test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Amphetamine test system. 862.3100 Section 862.3100....3100 Amphetamine test system. (a) Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements...

  12. In-sample derivatization-solid-phase microextraction of amphetamines and ecstasy related stimulants from water and urine.

    Science.gov (United States)

    Racamonde, Inés; Rodil, Rosario; Quintana, José Benito; Cela, Rafael

    2013-04-03

    A solid-phase microextraction (SPME) method for the determination of five amphetamine type stimulants (ATSs) in water and urine samples is presented. Analytes were simultaneously derivatized with iso-butyl chloroformate (iBCF) in the aqueous sample while being extracted, improving in this way the extractability of ATSs and permitting their determination by gas chromatography-mass spectrometry (GC-MS). The SPME procedure was carefully optimized in order to achieve adequate limits of detection (LODs) for environmental concentrations. Hence, different operational parameters were considered: type of SPME coating, ionic strength, basic catalyzer and derivatizing agent amount, extraction time and temperature. The final SPME procedure consists into the extraction of 100mL of sample containing 2 g of dipotassium monohydrogen phosphate trihydrate and 100 μL of iBCF (1:1 in acetonitrile), for 40 min at 60°C with a polydimethylsiloxane-divinylbenzene (PDMS-DVB) fiber. Under these conditions, LODs in wastewater ranged from 0.4 to 2 ng L(-1), relative recoveries in the 84-114% range and relative standard deviations (RSD) lower than 15% were obtained. The application of the method to wastewater and river water samples showed the ecstasy ATS, 3,4-methylenedioxymethamphetamine (MDMA), as the most frequently detected, followed by methamphetamine, in concentrations around 20 ng L(-1). Finally, the method was downscaled and also validated with urine samples, proving its good performance with this matrix too: RSD<11%, recoveries in the 98-110% range and LODs lower than 0.1 μg L(-1).

  13. Electrokinetic extraction on artificial liquid membranes of amphetamine-type stimulants from urine samples followed by high performance liquid chromatography analysis.

    Science.gov (United States)

    Seidi, Shahram; Yamini, Yadollah; Baheri, Tahmineh; Feizbakhsh, Rouhollah

    2011-07-01

    Electromembrane extraction (EME) coupled with high performance liquid chromatography and ultraviolet detection was developed for determination of amphetamine-type stimulants in human urine samples. Amphetamines migrated from 3 mL of different human urine matrices, through a thin layer of 2-nitrophenyl octyl ether (NPOE) containing 15% tris-(2-ethylhexyl) phosphate (TEHP) immobilized in the pores of a porous hollow fiber, and into a 15 μL acidic aqueous acceptor solution present inside the lumen of the fiber. Equilibrium extraction conditions were obtained after 7 min of operation. Experimental design and response surface methodology (RSM) were used for optimization of EME parameters. Under optimal conditions, amphetamines were effectively extracted with recoveries in the range of 54-70%, which corresponded to preconcentration factors in the range of 108-140. The calibration curves were investigated in the range of 0-7 μg mL(-1) and good linearity was achieved with a coefficient of estimation better than 0.991. Detection limits and inter-day precision (n=3) were less than 0.01 μg mL(-1) and 11.2%, respectively.

  14. Repeated administration of D-amphetamine induces loss of [{sup 123}I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    Energy Technology Data Exchange (ETDEWEB)

    Booij, Jan [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands)]. E-mail: j.booij@amc.uva.nl; Bruin, Kora de [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands); Gunning, W. Boudewijn [Department of Neurology, Epilepsy Centre Kempenhaeghe, 5590 AB Heeze (Netherlands)

    2006-04-15

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([{sup 123}I]FP-CIT). Methods: Groups of male rats (n=10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [{sup 123}I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. Results: In D-AMPH but not METH-treated rats, striatal [{sup 123}I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. Conclusion: These data show that [{sup 123}I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo.

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

    Science.gov (United States)

    Cox, Charles L.; Gulley, Joshua M.

    2016-01-01

    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 3 mg/kg AMPH (i.p.) during adolescence [postnatal day (P) 27 to P45] or adulthood (P85 to 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 (25 μM) 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

  16. Comparison of five derivatizing agents for the determination of amphetamine-type stimulants in human urine by extractive acylation and gas chromatography-mass spectrometry.

    Science.gov (United States)

    Dobos, Adrienn; Hidvégi, Elod; Somogyi, Gábor Pál

    2012-06-01

    Five acylation reagents have been compared for use as derivatizing agents for the analysis of amphetamine-type stimulants (ATS) in urine by gas chromatography-mass spectrometry (GC-MS). The evaluated reagents were heptafluorobutyric anhydride, pentafluoropropionic anhydride, trifluoroacetic anhydride, acetic anhydride (AA) and N-methyl-bis(trifluoroacetamide). The ATS included amphetamine, methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA). A mixture of the ATS was added to urine (1 mL) followed by KOH solution and saturated NaHCO(3) solution. The sample was then extracted with dichloromethane and the derivatizing agent and 2 µL were injected into the GC-MS instrument. The derivatizing agents were compared with reference to the signal-to-noise (S/N) ratios, peak area values, relative standard deviations (RSDs), linearities, limits of detection (LODs) and selectivities. The acetic anhydride proved to be the best according to the S/N ratio and peak area results for amphetamine, MA, MDMA and MDEA. The best RSD values of peak areas and of S/N ratios at 3 µg/mL were also given by AA in cases of MDA, MDMA and MDEA. At 20 µg/mL, the lowest RSD values of peak areas for MDA and the lowest RSD values of S/N ratios for MA, MDA, MDMA and MDEA were again given by AA. Additionally, the highest correlation coefficients for MA, MDA, MDMA and MDEA and the lowest LOD results for MA, MDMA and MDEA were produced by AA.

  17. Analysis of amphetamine-type stimulants and their metabolites in plasma, urine and bile by liquid chromatography with a strong cation-exchange column-tandem mass spectrometry.

    Science.gov (United States)

    Kuwayama, Kenji; Inoue, Hiroyuki; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Miyaguchi, Hajime; Iwata, Yuko T; Miyauchi, Seiji; Kamo, Naoki

    2008-05-01

    The aim of this work was to develop and validate a method for analysing amphetamine-type stimulants (ATSs) and their metabolites in plasma, urine and bile by liquid chromatography with a strong cation-exchange column-tandem mass spectrometry, and to apply it to the pharmacokinetic study of ATSs. 3,4-Methylenedioxymethamphetamine, methamphetamine, ketamine and their main metabolites, 4-hydroxy-3-methoxymethamphetamine, 3,4-methylenedioxyamphetamine, p-hydroxymethamphetamine, amphetamine and norketamine, were simultaneously quantified by the new method (50-5000 ng/ml). The coefficients of variation and the percent deviations for the eight compounds were in the range of 0.2 to 5.3% and -9.4 to +12.8%, respectively. The recoveries were over 90% in all biological samples tested. This method was effective for the separation and the identification of ATSs and their main metabolites having amine moieties in plasma, urine and bile, and was applicable to pharmacokinetic analysis of methamphetamine, ketamine and their main metabolites in biological samples. This analytical method should be useful for the pharmacokinetic analysis of ATSs.

  18. Stereoselective method development and validation for determination of concentrations of amphetamine-type stimulants and metabolites in human urine using a simultaneous extraction-chiral derivatization approach.

    Science.gov (United States)

    Wan Raihana, W A; Gan, S H; Tan, S C

    2011-01-01

    Amphetamine-type stimulants (ATS) are a group of chiral amine drugs which are commonly abused for their sympathomimetic and stimulant properties. ATS are extensively metabolised by hepatic cytochrome P450 enzymes. As metabolism of ATS has been shown to be highly stereospecific, stereoselective analytical methods are essential for the quantitative determination of ATS concentrations for both in vivo and in vitro studies of ATS metabolism. This paper describes a new stereoselective method for the simultaneous determination of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-hydroxymethamphetamine (HHMA) and 3,4-hydroxyamphetamine (HHA) in human urine samples validated according to the United States Food and Drug Administration guidelines. In this method, analytes are simultaneously extracted and derivatized with R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride (R-MTPCl) as the chiral derivatization reagent. Following this, the analytes were subjected to a second derivatization with N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) which targets the hydroxyl groups present in HMMA, HMA, HHMA and HHA. The derivatized analytes were separated and quantified using gas chromatography-mass spectrometry (GC-MS). The method was evaluated according to the established guidelines for specificity, linearity, precision, accuracy, recovery and stability using a five-day protocol. Intra-day precision ranged from 0.89 to 11.23% RSD whereas inter-day precision was between 1.03 and 12.95% RSD. Accuracy values for the analytes ranged from -5.29% to 13.75%. Limits of quantitation were 10 μg/L for AM, MA, MDMA, HMA and HMMA and 2μg/L for MDA, HMA and HHA. Recoveries and stability values were also within accepted values. The method was applied to authentic ATS-positive samples.

  19. Postural adaptations to repeated optic flow stimulation in older adults.

    Science.gov (United States)

    O'Connor, Kathryn W; Loughlin, Patrick J; Redfern, Mark S; Sparto, Patrick J

    2008-10-01

    The purpose of this study is to understand the processes of adaptation (changes in within-trial postural responses) and habituation (reductions in between-trial postural responses) to visual cues in older and young adults. Of particular interest were responses to sudden increases in optic flow magnitude. The postural sway of 25 healthy young adults and 24 healthy older adults was measured while subjects viewed anterior-posterior 0.4 Hz sinusoidal optic flow for 45 s. Three trials for each of three conditions were performed: (1) constant 12 cm optic flow amplitude (24 cm peak-to-peak), (2) constant 4 cm amplitude (8 cm p-t-p), and (3) a transition in amplitude from 4 to 12 cm. The average power of head sway velocity (P(vel)) was calculated for consecutive 5s intervals during the trial to examine the changes in sway within and between trials. A mixed factor repeated measures ANOVA was performed to examine the effects of subject Group, Trial, and Interval on the P(vel). P(vel) was greater in older adults in all conditions (phabituation. P(vel) of the older adults decreased significantly between all 3 trials, but decreased only between Trials 1 and 2 in young adults. While the responses of the young adults to the transition in optic flow from 4 to 12 cm did not significantly change, older adults had an increase in P(vel) following the transition, ranging from 6.5 dB for the first trial to 3.4 dB for the third trial. These results show that older adults can habituate to repeated visual perturbation exposures; however, this habituation requires a greater number of exposures than young adults. This suggests aging impacts the ability to quickly modify the relative weighting of the sensory feedback for postural stabilization.

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

    Science.gov (United States)

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

    2014-02-01

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

  1. Analysis of the effect of repeated-pulse transcranial magnetic stimulation at the Guangming point on electroencephalograms

    Institute of Scientific and Technical Information of China (English)

    Xin Zhang; Lingdi Fu; Yuehua Geng; Xiang Zhai; Yanhua Liu

    2014-01-01

    Here, we administered repeated-pulse transcranial magnetic stimulation to healthy people at the left Guangming (GB37) and a mock point, and calculated the sample entropy of electroencephalo-gram signals using nonlinear dynamics. Additionally, we compared electroencephalogram sample entropy of signals in response to visual stimulation before, during, and after repeated-pulse tran-scranial magnetic stimulation at the Guangming. Results showed that electroencephalogram sample entropy at left (F3) and right (FP2) frontal electrodes were significantly different depending on where the magnetic stimulation was administered. Additionally, compared with the mock point, electroencephalogram sample entropy was higher after stimulating the Guangming point. When visual stimulation at Guangming was given before repeated-pulse transcranial magnetic stimula-tion, signiifcant differences in sample entropy were found at ifve electrodes (C3, Cz, C4, P3, T8) in parietal cortex, the central gyrus, and the right temporal region compared with when it was given after repeated-pulse transcranial magnetic stimulation, indicating that repeated-pulse transcranial magnetic stimulation at Guangming can affect visual function. Analysis of electroencephalogram revealed that when visual stimulation preceded repeated pulse transcranial magnetic stimulation, sample entropy values were higher at the C3, C4, and P3 electrodes and lower at the Cz and T8 electrodes than visual stimulation followed preceded repeated pulse transcranial magnetic stimula-tion. The ifndings indicate that repeated-pulse transcranial magnetic stimulation at the Guangming evokes different patterns of electroencephalogram signals than repeated-pulse transcranial mag-netic stimulation at other nearby points on the body surface, and that repeated-pulse transcranial magnetic stimulation at the Guangming is associated with changes in the complexity of visually evoked electroencephalogram signals in parietal regions, central gyrus

  2. Female sex workers who use amphetamine-type stimulants (ATS) in three cities of Vietnam: use and sexual risks related to HIV/AIDS.

    Science.gov (United States)

    Ho, Hien Thi; Le, Giang Minh; Dinh, Thuy Thanh

    2013-01-01

    Early evidence shows that amphetamine-type stimulant (ATS) use has been rapidly increasing in Vietnam. Female sex workers (FSWs) who use ATSs have increased sexual risks for HIV infection. This paper presents qualitative data from a mixed-method study conducted from 2010 to 2011 that aimed to explore the use of ATS among FSWs in three major cities and to identify HIV-related sexual risks among this group. A total of 37 in-depth interviews were conducted, and thematic analysis was performed using NVIVO 8.0 software. Study participants reported that they perceive ATS to be more 'stylish', 'higher class' and much less 'addictive' than heroin. The study highlights multiple sexual risks among this group, including having prolonged sex; sex with multiple simultaneous partners or clients; lack of negotiation for safe sex; increased likelihood of group sex in the context of drug pooling and extended drug and sexual network; as well as unprotected sex. There is an urgent need to promote contextually appropriate interventions to reduce the HIV-related sexual risks among this group.

  3. Prolonged repeated acupuncture stimulation induces habituation effects in pain-related brain areas: an FMRI study.

    Science.gov (United States)

    Li, Chuanfu; Yang, Jun; Park, Kyungmo; Wu, Hongli; Hu, Sheng; Zhang, Wei; Bu, Junjie; Xu, Chunsheng; Qiu, Bensheng; Zhang, Xiaochu

    2014-01-01

    Most previous studies of brain responses to acupuncture were designed to investigate the acupuncture instant effect while the cumulative effect that should be more important in clinical practice has seldom been discussed. In this study, the neural basis of the acupuncture cumulative effect was analyzed. For this experiment, forty healthy volunteers were recruited, in which more than 40 minutes of repeated acupuncture stimulation was implemented at acupoint Zhusanli (ST36). Three runs of acupuncture fMRI datasets were acquired, with each run consisting of two blocks of acupuncture stimulation. Besides general linear model (GLM) analysis, the cumulative effects of acupuncture were analyzed with analysis of covariance (ANCOVA) to find the association between the brain response and the cumulative duration of acupuncture stimulation in each stimulation block. The experimental results showed that the brain response in the initial stage was the strongest although the brain response to acupuncture was time-variant. In particular, the brain areas that were activated in the first block and the brain areas that demonstrated cumulative effects in the course of repeated acupuncture stimulation overlapped in the pain-related areas, including the bilateral middle cingulate cortex, the bilateral paracentral lobule, the SII, and the right thalamus. Furthermore, the cumulative effects demonstrated bimodal characteristics, i.e. the brain response was positive at the beginning, and became negative at the end. It was suggested that the cumulative effect of repeated acupuncture stimulation was consistent with the characteristic of habituation effects. This finding may explain the neurophysiologic mechanism underlying acupuncture analgesia.

  4. Corticotropin-releasing hormone (CRH) stimulates cocaine- and amphetamine-regulated transcript gene (CART1) expression through CRH type 1 receptor (CRHR1) in chicken anterior pituitary.

    Science.gov (United States)

    Mo, Chunheng; Cai, Guoqing; Huang, Long; Deng, Qiuyang; Lin, Dongliang; Cui, Lin; Wang, Yajun; Li, Juan

    2015-12-01

    Cocaine- and amphetamine-regulated transcript (CART) peptide(s) is generally viewed as neuropeptide(s) and can control food intake in vertebrates, however, our recent study revealed that CART1 peptide is predominantly expressed in chicken anterior pituitary, suggesting that cCART1 peptide is a novel pituitary hormone in chickens and its expression is likely controlled by hypothalamic factor(s). To test this hypothesis, in this study, we examined the spatial expression of CART1 in chicken anterior pituitary and investigated the effect of hypothalamic corticotropin-releasing hormone (CRH) on pituitary cCART1 expression. The results showed that: 1) CART1 is expressed in both caudal and cephalic lobes of chicken anterior pituitary, revealed by quantitative real-time PCR (qPCR), western blot and immuno-histochemical staining; 2) CRH potently stimulates cCART1 mRNA expression in cultured chick pituitary cells, as examined by qPCR, and this effect is blocked by CP154526 (and not K41498), an antagonist specific for chicken CRH type I receptor (cCRHR1), suggesting that cCRHR1 expressed on corticotrophs mediates this action; 3) the stimulatory effect of CRH on pituitary cCART1 expression is inhibited by pharmacological drugs targeting the intracellular AC/cAMP/PKA, PLC/IP3/Ca(2+), and MEK/ERK signaling pathways. This finding, together with the functional coupling of these signaling pathways to cCRHR1 expressed in CHO cells demonstrated by luciferase reporter assay systems, indicates that these intracellular signaling pathways coupled to cCRHR1 can mediate CRH action. Collectively, our present study offers the first substantial evidence that hypothalamic CRH can stimulate pituitary CART1 expression via activation of CRHR1 in a vertebrate species.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  6. Organometallic macromolecules with piano stool coordination repeating units: chain configuration and stimulated solution behaviour.

    Science.gov (United States)

    Cao, Kai; Ward, Jonathan; Amos, Ryan C; Jeong, Moon Gon; Kim, Kyoung Taek; Gauthier, Mario; Foucher, Daniel; Wang, Xiaosong

    2014-09-11

    Theoretical calculations illustrate that organometallic macromolecules with piano stool coordination repeating units (Fe-acyl complex) adopt linear chain configuration with a P-Fe-C backbone surrounded by aromatic groups. The macromolecules show molecular weight-dependent and temperature stimulated solution behaviour in DMSO.

  7. Amphetamine-induced perseverative behavior in a radial arm maze following DSP4 or 6-OHDA pretreatment.

    Science.gov (United States)

    Bruto, V; Beauchamp, C; Zacharko, R M; Anisman, H

    1984-01-01

    Mice permitted to explore an 8-arm radial maze tended to visit those arms least recently entered. Treatment with D-amphetamine engendered a perseverative tendency, wherein mice repeatedly visited two arms of the maze. Administration of the norepinephrine (NE) neurotoxin, N-2-chloroethyl-N-ethyl-2-bromo-benzylamine (DSP4), appreciably reduced NE in the hippocampus and cortex, moderately reduced NE in the locus coeruleus, and had only a small effect on hypothalamic NE. The DSP4 treatment resulted in a decrease of locomotor activity among amphetamine-treated mice, coupled with an increase of stereotyped response patterns. Although the NE depletion did not affect the pattern of exploration that mice ordinarily displayed, DSP4 appreciably increased the perseverative tendency provoked by amphetamine. Reduction of dopamine (DA) and NE by intraventricular administration of the catecholamine neurotoxin, 6-hydroxydopamine (6-OHDA), antagonized the effects of amphetamine, such that the frequency of alternation responses was increased and the proportion of perseverative responses was reduced. The effectiveness of the 6-OHDA treatment in antagonizing the amphetamine-induced perseveration was not reduced among mice that were pretreated with desmethylimipramine, which resulted in partial prevention of the NE reduction by 6-OHDA administration. It is suggested that DA neuronal activity contributes to the amphetamine -provoked perseveration , whereas NE stimulation modifies the perseverative tendency by influencing exploration or habituation.

  8. Evidence for perceptual learning with repeated stimulation after partial and total cortical blindness.

    Science.gov (United States)

    Trevethan, Ceri T; Urquhart, James; Ward, Richard; Gentleman, Douglas; Sahraie, Arash

    2012-01-01

    Lesions of occipital cortex result in loss of sight in the corresponding regions of visual fields. The traditional view that, apart from some spontaneous recovery in the acute phase, field defects remain permanently and irreversibly blind, has been challenged. In patients with partial field loss, a range of residual visual abilities in the absence of conscious perception (blindsight) has been demonstrated (Weiskrantz, 1986). Recent findings (Sahraie et al., 2006, 2010) have also demonstrated increased visual sensitivity in the field defect following repeated stimulation. We aimed to extend these findings by systematically exploring whether repeated stimulation can also lead to increased visual sensitivity in two cases with total (bilateral) cortical blindness. In addition, for a case of partial blindness, we examined the extent of the recovery as a function of stimulated region of the visual field, over extended periods of visual training. Positive auditory feedback was provided during the training task for correct detection of a spatial grating pattern presented at specific retinotopic locations using a temporal two alternative forced-choice paradigm (Neuro-Eye Therapy). All three cases showed improved visual sensitivity with repeated stimulation. The findings indicate that perceptual learning can occur through systematic visual field stimulation even in cases of bilateral cortical blindness.

  9. Repeated transcranial direct current stimulation prevents abnormal behaviors associated with abstinence from chronic nicotine consumption.

    Science.gov (United States)

    Pedron, Solène; Monnin, Julie; Haffen, Emmanuel; Sechter, Daniel; Van Waes, Vincent

    2014-03-01

    Successful available treatments to quit smoking remain scarce. Recently, the potential of transcranial direct current stimulation (tDCS) as a tool to reduce craving for nicotine has gained interest. However, there is no documented animal model to assess the neurobiological mechanisms of tDCS on addiction-related behaviors. To address this topic, we have developed a model of repeated tDCS in mice and used it to validate its effectiveness in relieving nicotine addiction. Anodal repeated tDCS was applied over the frontal cortex of Swiss female mice. The stimulation electrode (anode) was fixed directly onto the cranium, and the reference electrode was placed onto the ventral thorax. A 2 × 20 min/day stimulation paradigm for five consecutive days was used (0.2 mA). In the first study, we screened for behaviors altered by the stimulation. Second, we tested whether tDCS could alleviate abnormal behaviors associated with abstinence from nicotine consumption. In naive animals, repeated tDCS had antidepressant-like properties 3 weeks after the last stimulation, improved working memory, and decreased conditioned place preference for nicotine without affecting locomotor activity and anxiety-related behavior. Importantly, abnormal behaviors associated with chronic nicotine exposure (ie, depression-like behavior, increase in nicotine-induced place preference) were normalized by repeated tDCS. Our data show for the first time in an animal model that repeated tDCS is a promising, non-expensive clinical tool that could be used to reduce smoking craving and facilitate smoking cessation. Our animal model will be useful to investigate the mechanisms underlying the effects of tDCS on addiction and other psychiatric disorders.

  10. Experience of clinical treatment to amphetamine-stimulants reliers%苯丙胺类兴奋剂依赖者临床治疗体会

    Institute of Scientific and Technical Information of China (English)

    卢金山; 吴峰; 张咏

    2011-01-01

    目的 总结苯丙胺类兴奋剂(amphetamin-type stimulants,ATS)依赖者的临床表现及治疗.方法 对104例符合DSM-Ⅳ诊断标准的ATS依赖者进行临床观察、治疗,并作出讨论.结果 ATS依赖者主要临床表现为:①中枢神经系统的作用.如精神兴奋、情感迸发、激动、感知觉障碍、定向障碍、精神病样反应、帕金森氏病样症状等.②系统作用.发热、心率快、血压高、食欲差、消瘦等.③戒断综合征.忧郁、焦虑、疲惫、全身肌肉疲软无力、头痛、固定型强迫行为等.治疗时,应建立一个安全、温馨的环境,给予患者充分的安慰,精神病样反应的患者给予其酚噻嗪类药物.结论 ATS是一种对中枢神经系统、心血管系统、人体行为有多种伤害作用的欢乐性兴奋剂.目前治疗只限于对症处理和进行长期严格监控、心理认知和行为干预.

  11. Correlates of amphetamine-type stimulants use and associations with HIV-related risks among young women engaged in sex work in Phnom Penh, Cambodia

    Science.gov (United States)

    Couture, Marie-Claude; Evans, Jennifer L.; Sothy, Neth San; Stein, Ellen S.; Sichan, Keo; Maher, Lisa; Page, Kimberly

    2011-01-01

    Background Amphetamine-type stimulant (ATS) use has increased in Cambodia and emerged as a significant problem among female sex workers (FSWs), potentially contributing to increased risk of HIV. We examined the prevalence of ATS use and its effect on sexual risk behaviors, and sexually transmitted infections (STI) among FSWs in Phnom Penh, Cambodia. Methods A one-year prospective study among young women engaged in sex work in brothels, entertainment establishments and on a freelance basis. Socio-demographics, sexual risks, and recent ATS use were assessed by self-report. Blood and urine samples were collected to detect HIV, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC). Bivariate and multivariate longitudinal analyses were conducted to assess the effects of ATS use on number of sex partners, inconsistent condom use with paying partners and incident STI. Results ATS use was higher among women working freelance (35.6%) and in brothels (34.8%) compared to women working in entertainment establishments (17.7%) or in multiple venues (14.8%). ATS users reported more sex partners and days drunk in the previous month. In multivariate longitudinal analysis, ATS use was associated with having a higher number of sex partners (Adjusted Risk Ratio 1.49; 95% CI: 1.00–2.21) and incident STI (Adjusted Odds Ratio 5.41; 95% CI: 1.15–25.48), but not inconsistent condom use with paying partner. Conclusion ATS users had more sex partners, high level of alcohol use, and were at increased risk of STI. Our findings underscore ATS use as an important emerging risk exposure that should be integrated into HIV prevention interventions targeting this population. PMID:21820251

  12. Prolonged repeated acupuncture stimulation induces habituation effects in pain-related brain areas: an FMRI study.

    Directory of Open Access Journals (Sweden)

    Chuanfu Li

    Full Text Available Most previous studies of brain responses to acupuncture were designed to investigate the acupuncture instant effect while the cumulative effect that should be more important in clinical practice has seldom been discussed. In this study, the neural basis of the acupuncture cumulative effect was analyzed. For this experiment, forty healthy volunteers were recruited, in which more than 40 minutes of repeated acupuncture stimulation was implemented at acupoint Zhusanli (ST36. Three runs of acupuncture fMRI datasets were acquired, with each run consisting of two blocks of acupuncture stimulation. Besides general linear model (GLM analysis, the cumulative effects of acupuncture were analyzed with analysis of covariance (ANCOVA to find the association between the brain response and the cumulative duration of acupuncture stimulation in each stimulation block. The experimental results showed that the brain response in the initial stage was the strongest although the brain response to acupuncture was time-variant. In particular, the brain areas that were activated in the first block and the brain areas that demonstrated cumulative effects in the course of repeated acupuncture stimulation overlapped in the pain-related areas, including the bilateral middle cingulate cortex, the bilateral paracentral lobule, the SII, and the right thalamus. Furthermore, the cumulative effects demonstrated bimodal characteristics, i.e. the brain response was positive at the beginning, and became negative at the end. It was suggested that the cumulative effect of repeated acupuncture stimulation was consistent with the characteristic of habituation effects. This finding may explain the neurophysiologic mechanism underlying acupuncture analgesia.

  13. Noradrenergic antagonists mitigate amphetamine-induced recovery.

    Science.gov (United States)

    Hylin, M J; Brenneman, M M; Corwin, J V

    2017-09-15

    Brain injury, including that due to stroke, leaves individuals with cognitive deficits that can disrupt daily aspect of living. As of now there are few treatments that shown limited amounts of success in improving functional outcome. The use of stimulants such as amphetamine have shown some success in improving outcome following brain injury. While the pharmacological mechanisms for amphetamine are known; the specific processes responsible for improving behavioral outcome following injury remain unknown. Understanding these mechanisms can help to refine the use of amphetamine as a potential treatment or lead to the use of other methods that share the same pharmacological properties. One proposed mechanism is amphetamine's impact upon noradrenaline (NA). In the current, study noradrenergic antagonists were administered prior to amphetamine to pharmacologically block α- and β-adrenergic receptors. The results demonstrated that the blockade of these receptors disrupted amphetamines ability to induce recovery from hemispatial neglect using an established aspiration lesion model. This suggests that amphetamine's ability to ameliorate neglect deficits may be due in part to noradrenaline. These results further support the role of noradrenaline in functional recovery. Finally, the development of polytherapies and combined therapeutics, while promising, may need to consider the possibility that drug interactions can negate the effectiveness of treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Functional and histologic changes after repeated transcranial direct current stimulation in rat stroke model.

    Science.gov (United States)

    Kim, Sang Jun; Kim, Byeong Kwon; Ko, Young Jin; Bang, Moon Suk; Kim, Man Ho; Han, Tai Ryoon

    2010-10-01

    Transcranial direct current stimulation (tDCS) is associated with enhancement or weakening of the NMDA receptor activity and change of the cortical blood flow. Therefore, repeated tDCS of the brain with cerebrovascular injury will induce the functional and histologic changes. Sixty-one Sprague-Dawley rats with cerebrovascular injury were used. Twenty rats died during the experimental course. The 41 rats that survived were allocated to the exercise group, the anodal stimulation group, the cathodal stimulation group, or the control group according to the initial motor function. Two-week treatment schedules started from 2 days postoperatively. Garcia, modified foot fault, and rota-rod performance scores were checked at 2, 9, and 16 days postoperatively. After the experiments, rats were sacrificed for the evaluation of histologic changes (changes of the white matter axon and infarct volume). The anodal stimulation and exercise groups showed improvement of Garcia's and modified foot fault scores at 16 days postoperatively. No significant change of the infarct volume happened after exercise and tDCS. Neuronal axons at the internal capsule of infarct hemispheres showed better preserved axons in the anodal stimulation group. From these results, repeated tDCS might have a neuroprotective effect on neuronal axons in rat stroke model.

  15. Simultaneous qualitative and quantitative method using liquid chromatography selected reaction monitoring-triggered quantitation-enhanced data-dependent tandem mass spectrometry for the identification and classification of amphetamine-type stimulant abusers in human urine.

    Science.gov (United States)

    Lee, Sang Kyu; Kim, So-Hee; Kim, Ho Jun; Yoo, Hye Hyun; Kwon, Oh Seung; In, Moon Kyo; Jin, Changbae; Kim, Dong Hyun; Lee, Jaeick

    2010-11-15

    Amphetamine (AP) and amphetamine-type stimulants, methamphetamine (MA) and N,N-dimethylamphetamine (DMA), are known as central nervous system stimulants, and their abuse throughout the world has recently increased. Since it is difficult to physically distinguish among AP, MA and DMA, analysts may not be aware of what abusers have administered. In this study, following the detection of specific metabolites of AP, MA and DMA as biomarkers in abuser urines, a rapid and sensitive method was developed for the identification and classification of AP-type stimulants abusers. After the simple filtration of the urine samples, the samples were directly analyzed using a liquid chromatography/tandem mass spectrometry system with selected reaction monitoring (SRM)-triggered quantitation-enhanced data-dependent MS/MS (QED-MS/MS) for the simultaneous qualitative and quantitative analysis of p-hydroxy AP, p-hydroxy MA, p-hydroxy DMA, AP, MA, DMA and DMA N-oxide. The determination of p-hydroxy AP, p-hydroxy MA, AP, MA, DMA and DMA N-oxide was accurate and reproducible, with the limits of quantitation of 5 ng/mL in urine. When applied to the urine samples of suspected AP-type stimulants abusers, the abused drugs were precisely identified between MA and DMA abusers.

  16. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, Sherin T.; Bergström, Petra; Hammarsten, Ola, E-mail: ola.hammarsten@clinchem.gu.se

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2′-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. - Highlights: • Repeated treatment with sulforaphane protects fibroblasts from ionizing radiation • Repeated sulforaphane treatment attenuates radiation induced ROS and DNA damage • Sulforaphane mediated protection is Nrf2 dependent.

  17. Frequency-dependent entrainment of neocortical slow oscillation to repeated optogenetic stimulation in the anesthetized rat.

    Science.gov (United States)

    Kuki, Toshinobu; Ohshiro, Tomokazu; Ito, Shin; Ji, Zhi-Gang; Fukazawa, Yugo; Matsuzaka, Yoshiya; Yawo, Hiromu; Mushiake, Hajime

    2013-01-01

    Local field potential (LFP) slow oscillation (entrained to repeated external sensory stimuli. To better understand the neural mechanism underlying slow-oscillation generation and its entrainment to external stimuli, we delivered optical stimulation to the cortex of anesthetized rats that exogenously expressed the light-sensitive cation channel channelrhodopsin-2 (ChR2) and simultaneously monitored LFPs across cortical layers. We found that the LFPs could be effectively entrained to repeated optical stimulation at 1Hz in deep layers. A stimulus-triggered current-source density (CSD) analysis showed that the evoked oscillation had the same depth and temporal profile as the slow oscillations, indicating that both oscillations have the same neural mechanism. Optical stimulation primarily induced the transition from the cortical up to down state. These results suggest that the anesthetized rat cortex has an intrinsic mechanism that leads to oscillation near 1Hz; effective entrainment to the 1Hz stimulation reflects the resonated state of the cortex to that stimulus. Our study is the first to demonstrate optogenetic manipulation of cortical slow oscillation and provides a mechanistic explanation for slow-oscillation entrainment.

  18. Amphetamine derivative related deaths.

    Science.gov (United States)

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

    1997-02-28

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

  19. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation.

    Science.gov (United States)

    Mathew, Sherin T; Bergström, Petra; Hammarsten, Ola

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2'-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Amphetamine availability and admissions for psychosis in New South Wales, 2001-2009.

    Science.gov (United States)

    Sara, Grant; Burgess, Philip; Malhi, Gin; Whiteford, Harvey

    2011-04-01

    Clinicians have raised concerns about the impact of amphetamines on demand for mental health services. However, evidence for this link is limited. This study explores whether changes in the availability of amphetamines in NSW in the last decade have been associated with variations in admission to mental health units for amphetamine related conditions and for psychoses more generally. The study examined admissions from community settings to NSW acute mental health units from 2000 to 2009. Quarterly rates of hospital admission with primary or comorbid diagnoses of stimulant use disorders, stimulant-induced psychoses and non-drug-related psychoses were compared to quarterly rates of criminal incidents of amphetamine possession and use, which provide an indirect measure of the community availability of amphetamines. Analysis was confounded by increases in mental health beds over the period. Linear regression predicted admission rates on the basis of amphetamine availability, adjusting for changing mental health bed numbers. Amphetamine availability and admissions for psychoses increased steadily from 2000 to a peak in early 2007, but have declined since. Regression models including both amphetamine availability and bed numbers predicted 34% of variation in stimulant use disorders admission rates and 50% of variation in stimulant induced psychoses admission rates. There was no significant effect of amphetamine availability on admissions for schizophrenia and other non-drug-induced psychoses after controlling for changing bed numbers. Increased amphetamine availability appears to have been one factor increasing demand for mental health admission in NSW over the last decade. However, there appears to have been a recent downward trend in both amphetamine availability and amphetamine-related admissions. Policies which reduce the community availability of amphetamines may result in reduced admissions for amphetamine-related mental health conditions, including amphetamine

  1. Repeated administration of D-amphetamine induces loss of [I-123]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    NARCIS (Netherlands)

    J. Booij; K. de Bruin; W.B. Gunning

    2006-01-01

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in arnphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of

  2. Atrial natriuretic peptide stimulates lipid mobilization during repeated bouts of endurance exercise.

    Science.gov (United States)

    Moro, Cédric; Polak, Jan; Hejnova, Jindra; Klimcakova, Eva; Crampes, François; Stich, Vladimir; Lafontan, Max; Berlan, Michel

    2006-05-01

    Atrial natriuretic peptide (ANP) controls lipolysis in human adipocytes. Lipid mobilization is increased during repeated bouts of exercise, but the underlying mechanisms involved in this process have not yet been delineated. The relative involvement of catecholamine- and ANP-dependent pathways in the control of lipid mobilization during repeated bouts of exercise was thus investigated in subcutaneous adipose tissue (SCAT) by microdialysis. The study was performed in healthy males. Subjects performed two 45-min exercise bouts (E1 and E2) at 50% of their maximal oxygen uptake separated by a 60-min rest period. Extracellular glycerol concentration (EGC), reflecting SCAT lipolysis, was measured in a control probe perfused with Ringer solution and in two other probes perfused with either Ringer plus phentolamine (alpha(1/2)-AR antagonist) or Ringer plus both phentolamine and propranolol (beta-AR antagonist). Plasma epinephrine, plasma glycerol, and EGC were 1.7-, 1.6-, and 1.2-fold higher in E2 than in E1, respectively. Phentolamine potentiated exercise-induced EGC increase during E2 only. Propranolol reduced the lipolytic rate during both E1 and E2 compared with the probe with phentolamine. Plasma ANP concentration increased more during E2 than during E1 and was correlated with the increase in EGC in the probe containing phentolamine plus propranolol. The results suggest that ANP is involved in the control of lipolysis during exercise and that it contributes to stimulation of lipolysis during repeated bouts of exercise.

  3. Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Greiff Lennart

    2012-06-01

    Full Text Available Abstract Background Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. Objective To evaluate the efficacy and safety of intranasal AZD8848. Methods In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779. In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003. Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. Results AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848. Conclusions Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis. Trial registration NCT00688779 and NCT00770003 as indicated above.

  4. Repeated Microneedle Stimulation Induces Enhanced Hair Growth in a Murine Model

    Science.gov (United States)

    Kim, Yoon Seob; Jeong, Kwan Ho; Kim, Jung Eun; Woo, Young Jun; Kim, Beom Joon

    2016-01-01

    Background Microneedle is a method that creates transdermal microchannels across the stratum corneum barrier layer of skin. No previous study showed a therapeutic effect of microneedle itself on hair growth by wounding. Objective The aim of this study is to investigate the effect of repeated microwound formed by microneedle on hair growth and hair growth-related genes in a murine model. Methods A disk microneedle roller was applied to each group of mice five times a week for three weeks. First, to identify the optimal length and cycle, microneedles of lengths of 0.15 mm, 0.25 mm, 0.5 mm, and 1 mm and cycles of 3, 6, 10, and 13 cycles were applied. Second, the effect of hair growth and hair-growth-related genes such as Wnt3a, β-catenin, vascular endothelial growth factor (VEGF), and Wnt10b was observed using optimized microneedle. Outcomes were observed using visual inspection, real-time polymerase chain reaction, and immunohistochemistry. Results We found that the optimal length and cycle of microneedle treatment on hair growth was 0.25 mm/10 cycles and 0.5 mm/10 cycles. Repeated microneedle stimulation promoted hair growth, and it also induced the enhanced expression of Wnt3a, β-catenin, VEGF, and Wnt10b. Conclusion Our study provides evidence that microneedle stimulation can induce hair growth via activation of the Wnt/β-catenin pathway and VEGF. Combined with the drug delivery effect, we believe that microneedle stimulation could lead to new approaches for alopecia. PMID:27746638

  5. DNA tandem repeat instability in the Escherichia coli chromosome is stimulated by mismatch repair at an adjacent CAG·CTG trinucleotide repeat

    Science.gov (United States)

    Blackwood, John K.; Okely, Ewa A.; Zahra, Rabaab; Eykelenboom, John K.; Leach, David R. F.

    2010-01-01

    Approximately half the human genome is composed of repetitive DNA sequences classified into microsatellites, minisatellites, tandem repeats, and dispersed repeats. These repetitive sequences have coevolved within the genome but little is known about their potential interactions. Trinucleotide repeats (TNRs) are a subclass of microsatellites that are implicated in human disease. Expansion of CAG·CTG TNRs is responsible for Huntington disease, myotonic dystrophy, and a number of spinocerebellar ataxias. In yeast DNA double-strand break (DSB) formation has been proposed to be associated with instability and chromosome fragility at these sites and replication fork reversal (RFR) to be involved either in promoting or in preventing instability. However, the molecular basis for chromosome fragility of repetitive DNA remains poorly understood. Here we show that a CAG·CTG TNR array stimulates instability at a 275-bp tandem repeat located 6.3 kb away on the Escherichia coli chromosome. Remarkably, this stimulation is independent of both DNA double-strand break repair (DSBR) and RFR but is dependent on a functional mismatch repair (MMR) system. Our results provide a demonstration, in a simple model system, that MMR at one type of repetitive DNA has the potential to influence the stability of another. Furthermore, the mechanism of this stimulation places a limit on the universality of DSBR or RFR models of instability and chromosome fragility at CAG·CTG TNR sequences. Instead, our data suggest that explanations of chromosome fragility should encompass the possibility of chromosome gaps formed during MMR. PMID:21149728

  6. Identification of Amphetamine-type Stimulants Using Gas Chromatography Coupled with Fourier Transform Infrared Spectroscopy%苯丙胺类毒品及其衍生物的气相色谱-红外光谱分析

    Institute of Scientific and Technical Information of China (English)

    张润生; 王跨陡; 龚飞君; 叶海英; 张玉荣; 严松茂; 杜一平; 张维冰

    2012-01-01

    采用气相色谱一傅立叶变换红外光谱联用技术,建立了9种苯丙胺类毒品及其衍生物的分析鉴别方法.采用HP-1(30 m×0.32 mm,0.25 μm)毛细管柱,MCT红外检测器与氢火焰检测器同时检测,在程序升温条件下,以十七烷为内标物,研究已知对照品的色谱保留行为及其气态红外光谱图特征,建立相应的特征吸收峰数据库,作为鉴别分析的依据.色谱保留时间与红外特征吸收峰联合鉴别法极大地提高了鉴别的准确性.将发展的方法应用于可疑毒品物证中苯丙胺类及其衍生物毒品样品的鉴别,获得了理想的结果.本方法可用于涉毒案件毒品物证的检验,特别适用于混合毒品成分的检验.%Gas chromatography-infrared spectroscopy technique has been used for the quantitative analysis of amphetamine-type stimulants. Capillary column of HP-1 (30 m×0. 32 mm. 0. 25 μm) was coupled with MCT infrared spectroscopy and flame ionization detecters using temperature programming for identification of nine ampletamine-type stimulants. Chromatographic retention behaviors were studied using heptadecane as internal standard for separation and identification of the stimulants. On another hand, infrared spectra of the gaseous amphetamine-type stimulants were measured using chemical reference substances of the stimulants and the characteristic peaks from the collected spectra were supplied as an assistant identification. The cooperation of information from retention time and infrared spectrum should improve the reliability of the method. The analysis of real samples showed satisfactory results. The method could be applied to the stimulant identification, especially to that of complicated sample.

  7. Substance use - amphetamines

    Science.gov (United States)

    ... Others use them to boost their performance in sports. Amphetamines also cause the brain to release dopamine. ... thinking clearly Mood and emotional problems such as aggressive or violent behavior Restlessness and tremors Skin sores Sleep problems Tooth ...

  8. D-amphetamine and delinquency: hyperkinesis persisting?

    Science.gov (United States)

    Maletzky, B M

    1974-12-01

    might be responsible. The early uncontrolled studies of Hill in this regard (summarized in 1947), suggesting that d, l-amphetamine was helpful with some delinquent adolescents, seem largely to have been forgotten. Hill believed that among a large group of delinquents, some, characterized by impulsive irritability, violence, late cessation of nocturnal eneuresis, and a familial history of epilepsy, benefited by a reduction of impulsivity with amphetamine; both early and recent workers remark on a similar reduction in impulsivity when stimulants are successfully used in younger hyperactive children. Eisenberg and coworkers have reported the only controlled study of stimulants in delinquency. These investigators found d-amphetamines superior to placebo on teachers' and cottage-parents' ratings in institutionalized Negro boys. Unfortunately, much of the statistical work in this report is uneven because of factors beyond the control of the researchers. Moreover, an unvalidated symptom check list was employed with no report of which specific symptoms were improved with the drug and which not. The present report attempts a further analysis of stimulants in delinquency. It is constructed to answer the following questions: 1. Is d-amphetamine significantly superior to placebo in controlling delinquent behavior? 2. Are there specific symptom clusters for which d-amphetamine is especially helpful? Thus, is there a prototypical delinquent responder to d-amphetamine? 3. If so, is this information helpful in assessing the association between hyperactivity of childhood and delinquency of adolescence?

  9. 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.

  10. Amphetamine Sensitization Alters Reward Processing in the Human Striatum and Amygdala

    Science.gov (United States)

    O’Daly, Owen G.; Joyce, Daniel; Tracy, Derek K.; Azim, Adnan; Stephan, Klaas E.; Murray, Robin M.; Shergill, Sukhwinder S.

    2014-01-01

    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. PMID:24717936

  11. 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.

  12. Urethralism concomitant with amphetamine abuse

    Directory of Open Access Journals (Sweden)

    Bang-Ping Jiann

    2014-09-01

    Full Text Available Urethralism is a paraphilia disorder in which a person exhibits the habitual self-insertion of a foreign body into the urethra to achieve sexual gratification. We report a patient who habitually inserted a foreign body into his urethra and abused amphetamines to cope with stress. A 48-year-old man presented at the emergency room because of urine leakage from the penile base. Prior to this incident, he had been admitted to hospital 10 times from 2000 to 2005 for the removal of foreign bodies from the lower urinary tract. The patient also reported repeatedly inhaling a high dose of amphetamine to reach a “high” status prior to inserting a foreign body into his urethra. After the successful removal of the foreign bodies, the patient was referred to a psychiatrist for management in coping with stress and illicit drug withdrawal. Psychiatric support and treatment appeared to have a beneficial effect on his sexual behavior. In the management of a case involving recurrent insertion of a foreign body into the lower urinary tract, clinicians should enquire about a history of drug abuse and consult the psychiatry department regarding stress management and drug abstinence.

  13. Central adaptation to repeated galvanic vestibular stimulation: implications for pre-flight astronaut training.

    Directory of Open Access Journals (Sweden)

    Valentina Dilda

    Full Text Available Healthy subjects (N = 10 were exposed to 10-min cumulative pseudorandom bilateral bipolar Galvanic vestibular stimulation (GVS on a weekly basis for 12 weeks (120 min total exposure. During each trial subjects performed computerized dynamic posturography and eye movements were measured using digital video-oculography. Follow up tests were conducted 6 weeks and 6 months after the 12-week adaptation period. Postural performance was significantly impaired during GVS at first exposure, but recovered to baseline over a period of 7-8 weeks (70-80 min GVS exposure. This postural recovery was maintained 6 months after adaptation. In contrast, the roll vestibulo-ocular reflex response to GVS was not attenuated by repeated exposure. This suggests that GVS adaptation did not occur at the vestibular end-organs or involve changes in low-level (brainstem-mediated vestibulo-ocular or vestibulo-spinal reflexes. Faced with unreliable vestibular input, the cerebellum reweighted sensory input to emphasize veridical extra-vestibular information, such as somatosensation, vision and visceral stretch receptors, to regain postural function. After a period of recovery subjects exhibited dual adaption and the ability to rapidly switch between the perturbed (GVS and natural vestibular state for up to 6 months.

  14. Possible stimulation of anti-tumor immunity using repeated cold stress: a hypothesis

    Directory of Open Access Journals (Sweden)

    Radoja Sasa

    2007-11-01

    Full Text Available Abstract Background The phenomenon of hormesis, whereby small amounts of seemingly harmful or stressful agents can be beneficial for the health and lifespan of laboratory animals has been reported in literature. In particular, there is accumulating evidence that daily brief cold stress can increase both numbers and activity of peripheral cytotoxic T lymphocytes and natural killer cells, the major effectors of adaptive and innate tumor immunity, respectively. This type of regimen (for 8 days has been shown to improve survival of mice infected with intracellular parasite Toxoplasma gondii, which would also be consistent with enhanced cell-mediated immunity. Presentation of the hypothesis This paper hypothesizes that brief cold-water stress repeated daily over many months could enhance anti-tumor immunity and improve survival rate of a non-lymphoid cancer. The possible mechanism of the non-specific stimulation of cellular immunity by repeated cold stress appears to involve transient activation of the sympathetic nervous system, hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes, as described in more detail in the text. Daily moderate cold hydrotherapy is known to reduce pain and does not appear to have noticeable adverse effects on normal test subjects, although some studies have shown that it can cause transient arrhythmias in patients with heart problems and can also inhibit humoral immunity. Sudden immersion in ice-cold water can cause transient pulmonary edema and increase permeability of the blood-brain barrier, thereby increasing mortality of neurovirulent infections. Testing the hypothesis The proposed procedure is an adapted cold swim (5–7 minutes at 20 degrees Celsius, includes gradual adaptation to be tested on a mouse tumor model. Mortality, tumor size, and measurements of cellular immunity (numbers and activity of peripheral CD8+ T lymphocytes and natural killer cells of the cold-exposed group would be compared to

  15. Class identity assignment for amphetamines using neural networks and GC-FTIR data

    Science.gov (United States)

    Gosav, S.; Praisler, M.; Van Bocxlaer, J.; De Leenheer, A. P.; Massart, D. L.

    2006-08-01

    An exploratory analysis was performed in order to evaluate the feasibility of building of neural network (NN) systems automating the identification of amphetamines necessary in the investigation of drugs of abuse for epidemiological, clinical and forensic purposes. A first neural network system was built to distinguish between amphetamines and nonamphetamines. A second, more refined system, aimed to the recognition of amphetamines according to their toxicological activity (stimulant amphetamines, hallucinogenic amphetamines, nonamphetamines). Both systems proved that discrimination between amphetamines and nonamphetamines, as well as between stimulants, hallucinogens and nonamphetamines is possible (83.44% and 85.71% correct classification rate, respectively). The spectroscopic interpretation of the 40 most important input variables (GC-FTIR absorption intensities) shows that the modeling power of an input variable seems to be correlated with the stability and not with the intensity of the spectral interaction. Thus, discarding variables only because they correspond to spectral windows with weak absorptions does not seem be not advisable.

  16. Transitory FGF treatment results in the long-lasting suppression of the proliferative response to repeated FGF stimulation.

    Science.gov (United States)

    Poole, Ashleigh; Knowland, Nicholas; Cooper, Emily; Cole, Rebecca; Wang, Hongchuan; Booth, Lucas; Kacer, Doreen; Tarantini, Francesca; Friesel, Robert; Prudovsky, Igor

    2014-05-01

    FGF applied as a single growth factor to quiescent mouse fibroblasts induces a round of DNA replication, however continuous stimulation results in arrest in the G1 phase of the next cell cycle. We hypothesized that FGF stimulation induces the establishment of cell memory, which prevents the proliferative response to repeated or continuous FGF application. When a 2-5 days quiescence period was introduced between primary and repeated FGF treatments, fibroblasts failed to efficiently replicate in response to secondary FGF application. The establishment of "FGF memory" during the first FGF stimulation did not require DNA synthesis, but was dependent on the activity of FGF receptors, MEK, p38 MAPK and NFκB signaling, and protein synthesis. While secondary stimulation resulted in strongly decreased replication rate, we did not observe any attenuation of morphological changes, Erk1/2 phosphorylation and cyclin D1 induction. However, secondary FGF stimulation failed to induce the expression of cyclin A, which is critical for the progression from G1 to S phase. Treatment of cells with a broad range histone deacetylase inhibitor during the primary FGF stimulation rescued the proliferative response to the secondary FGF treatment suggesting that the establishment of "FGF memory" may be based on epigenetic changes. We suggest that "FGF memory" can prevent the hyperplastic response to cell damage and inflammation, which are associated with an enhanced FGF production and secretion. "FGF memory" may present a natural obstacle to the efficient application of recombinant FGFs for the treatment of ulcers, ischemias, and wounds.

  17. The Clinical Features of Mental Disorder Due to Amphetamine Type Stimulants%苯丙胺类兴奋剂所致精神障碍临床特征分析

    Institute of Scientific and Technical Information of China (English)

    杨拓; 刘丽; 马力; 张陆贤

    2015-01-01

    目的:探讨苯丙胺类兴奋剂所致精神障碍临床特点。方法对2010~2013年在南宁市社会福利医院药物依赖科住院治疗的132例ATS所致精神病性障碍临床资料进行回顾性分析。结果滥用ATS类兴奋剂男女性别差异不大,文化素质偏低职业以无业和个体为主。76例(57.6%)曾经使用或合并使用其他物质。常见的精神病性症状为幻听112例(84.8%)、被害妄想124例(93.9%)、嫉妒妄想96例(72.7%)、易激惹120例(90.9%)、兴奋状态124例(93.9%)、冲动行为104例(78.8%)。经治疗症状在一个月内显效率97.4%。结论长期滥用苯丙胺类兴奋剂可致严重的精神病性障碍。治疗以对症治疗为主,并辅以心理治疗,总体疗效尚佳。%Objective To discuss the clinical features of mental disorder due to amphetamine type stimulants. Methods 132 Clinical data of psychotic disorder caused by ATS were retrospectively was analyzed from 2010 to 2013 in Nanning City Social Welfare Institute in Drug Dependence department. Results The abuse of amphetamine type stimulants had no sex difference. The low cultural quality was to unemployed and individual. 19 cases(57.6%)had used or combined with other substances. Psychotic symptoms common to auditory hal ucinations in 28 cases(84.8%),31(93.9%)cases of paranoia, delusions of jealousy in 24 cases(72.7%),irritable in 30 cases(90.9%),the excited state in 31 cases(93.9%),impulsive behavior in 26 cases(78.8%). After treatment,the significantly efficiency of symptoms was 97.4% within a month. Conclusion The mental disorders can be severe if abuse amphetamine type stimulants. Symptomatic treatment,supplemented by psychological treatment,the overal effect is comparatively good.

  18. MiRNAs在苯丙胺类兴奋剂成瘾中作用的研究进展%Research progress on the role of miRNAs in amphetamine-type stimulants addiction

    Institute of Scientific and Technical Information of China (English)

    江明金; 李婵; 林莹波; 朱道琦; 莫志贤

    2015-01-01

    Amphetamine-type stimulants ( ATS ) , a group of new-type synthetic drugs mainly in psychological dependence, are abused more and more severely in recent years. MicroRNAs ( MiRNAs ) are an important class of endogenous non-coding small RNAs that mediate posttranscriptional negatively regulation of gene expression by targeting specific mRNA sequences to in-hibit the translation of mRNAs or degrade the expression of mR-NAs. ATS can induce the changes in the expression of miRNAs in addiction-related brain regions which directly involve in the regulation of ATS-induced addictive behaviors. Therefore, to study the regulatory role of miRNAs in ATS-induced addiction has important implications for dependent mechanisms of new-type drugs and the discovery of the new targets of drug actions.%苯丙胺类兴奋剂( amphetamine-type stimulants,ATS)是一组以精神依赖为主的新型合成毒品,近年来流行,滥用趋势愈发严峻。 MicroRNAs( MiRNAs)作为一类非编码小分子RNAs,通过与靶基因mRNA的互补配对,在转录后水平上对基因的表达进行负调控,从而导致靶基因mRNA的降解或翻译抑制。 ATS能诱导miRNAs表达水平的变化,而成瘾相关脑区miRNAs表达的改变直接参与了对ATS成瘾行为的调节。因此,研究miRNAs在ATS成瘾中的调控作用,对进一步揭示新型毒品的成瘾机制及发现新的药物作用靶点具有重要意义。

  19. Amphetamines and Sports Performance.

    Science.gov (United States)

    Cooter, G. Rankin

    1980-01-01

    A large number of athletes have resorted to drugs to improve performance in competition. Research literature on the use of amphetamines, both pro and con, is currently confounded with poor research designs and lack of controls, and further research is needed. (CJ)

  20. Prolonged Repeated Acupuncture Stimulation Induces Habituation Effects in Pain-Related Brain Areas: An fMRI Study

    Science.gov (United States)

    Li, Chuanfu; Yang, Jun; Park, Kyungmo; Wu, Hongli; Hu, Sheng; Zhang, Wei; Bu, Junjie; Xu, Chunsheng; Qiu, Bensheng; Zhang, Xiaochu

    2014-01-01

    Most previous studies of brain responses to acupuncture were designed to investigate the acupuncture instant effect while the cumulative effect that should be more important in clinical practice has seldom been discussed. In this study, the neural basis of the acupuncture cumulative effect was analyzed. For this experiment, forty healthy volunteers were recruited, in which more than 40 minutes of repeated acupuncture stimulation was implemented at acupoint Zhusanli (ST36). Three runs of acupuncture fMRI datasets were acquired, with each run consisting of two blocks of acupuncture stimulation. Besides general linear model (GLM) analysis, the cumulative effects of acupuncture were analyzed with analysis of covariance (ANCOVA) to find the association between the brain response and the cumulative duration of acupuncture stimulation in each stimulation block. The experimental results showed that the brain response in the initial stage was the strongest although the brain response to acupuncture was time-variant. In particular, the brain areas that were activated in the first block and the brain areas that demonstrated cumulative effects in the course of repeated acupuncture stimulation overlapped in the pain-related areas, including the bilateral middle cingulate cortex, the bilateral paracentral lobule, the SII, and the right thalamus. Furthermore, the cumulative effects demonstrated bimodal characteristics, i.e. the brain response was positive at the beginning, and became negative at the end. It was suggested that the cumulative effect of repeated acupuncture stimulation was consistent with the characteristic of habituation effects. This finding may explain the neurophysiologic mechanism underlying acupuncture analgesia. PMID:24821143

  1. Amphetamine enhances retrieval following diverse sources of forgetting.

    Science.gov (United States)

    Quartermain, D; Judge, M E; Jung, H

    1988-01-01

    The generality of amphetamine-induced retrieval enhancement was investigated by determining whether pretest administration could alleviate different types of forgetting. Thirsty mice were punished for licking a water tube following a period of free drinking. Forgetting of the conditioned drink suppression was induced in different groups of animals by; protein synthesis inhibition, cholinergic receptor blockade, inhibition of norepinephrine synthesis, stimulation of serotonin receptors, electroconvulsive shock, a 2.5 month training to test interval and the use of senescent animals with an endogenous memory defect. Thirty min prior to testing mice were injected with either saline or with 2 mg/kg d-amphetamine sulphate. Results showed that amphetamine produced a highly significant improvement in remembering in all of the forgetting treatment groups. It is concluded that amphetamine can alleviate forgetting caused by widely diverse etiologies probably by activating a nonspecific general retrieval system.

  2. 苯丙胺类物质滥用者高危行为性别差异的分析%THE CHARACTERISTIC OF HIGH-RISK BEHAVIOR AND THE GENDER DIFFERENCES IN AMPHETAMINE-TYPE STIMULANTS USERS

    Institute of Scientific and Technical Information of China (English)

    杜哲一; 李质彬; 陶凤英; 孙海明; 陈志康; 杜江; 赵敏

    2014-01-01

    目的:了解不同性别苯丙胺类物质(amphetamine-type stimulants,ATS))滥用者一般人口学特征、毒品使用情况和高危行为的差异.方法:采用横断面调查研究,对来自上海强制隔离戒毒所的377名ATS滥用者进行调查.结果:不同性别的ATS滥用者在毒品滥用史,高危行为方面存在显著差异.女性患者首次使用年龄较男性更早,使用ATS后发生即刻性行为、有多个性伴侣的比例均高于男性,且性伴侣在性行为中更少使用安全套.此外,女性患者更多出现自杀观念和自杀行为.而男性患者使用ATS后的性冲动显著高于女性.结论:不同性别的ATS滥用者在毒品使用及高危行为方面存在差异.工作人员应当对不同性别的使用者制定针对性的干预措施.

  3. Young women engaged in sex work in Phnom Penh, Cambodia, have high incidence of HIV and sexually transmitted infections, and amphetamine-type stimulant use: new challenges to HIV prevention and risk.

    Science.gov (United States)

    Couture, Marie-Claude; Sansothy, Neth; Sapphon, Vonthanak; Phal, Serey; Sichan, Keo; Stein, Ellen; Evans, Jennifer; Maher, Lisa; Kaldor, John; Vun, Mean Chhi; Page, Kimberly

    2011-01-01

    To estimate prevalence and incidence of HIV and sexually transmitted infections (STI) and associated risk factors among young women working as sex workers (SWs) in Phnom Penh, Cambodia. A prospective study of young (freelance. Sociodemographics, sexual risk, and use of amphetamine-type stimulants (ATS) ("yama" and "crystal") were assessed by self-report. HIV and STI (Chlamydia trachomatis and Neisseria gonorrhoeae) testing were conducted on blood and urine specimens, respectively. Baseline prevalences of HIV, C. trachomatis, and N. gonorrhoeae were 23%, 11.5%, and 7.8%, respectively. HIV incidence was 3.6 per 100 person-years (95% confidence interval [CI], 1.2%-11.1%); STI incidence was 21.2 per 100 person-years (95% CI, 12.6%-35.8%). At baseline, 26.5% reported recent ATS use. HIV infection was associated with freelance SW (adjusted odds ratio, 5.85; 95% CI, 1.59-21.58) and younger age of first sex (≤15 years; adjusted odds ratio, 3.06; 95% CI, 1.01-8.46). Incident STI was associated with duration (per year) of SW (adjusted hazard ratio, 1.1; 95% CI, 1.1-1.2) and recent yama use (adjusted hazard ratio, 3.9; 95% CI, 1.5-10.3). HIV and STI infection rates were high among SWs working in various settings; freelancers had highest risk. ATS use was associated with incident STI. Venue of sex work and drug prevention should be considered in prevention programs.

  4. 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.

  5. Modulation of neuropeptide FF (NPFF) receptors influences the expression of amphetamine-induced conditioned place preference and amphetamine withdrawal anxiety-like behavior in rats.

    Science.gov (United States)

    Kotlinska, J H; Gibula-Bruzda, E; Koltunowska, D; Raoof, H; Suder, P; Silberring, J

    2012-01-01

    Many data indicate that endogenous opioid system is involved in amphetamine-induced behavior. Neuropeptide FF (NPFF) possesses opioid-modulating properties. The aim of the present study was to determine whether pharmacological modulation of NPFF receptors modify the expression of amphetamine-induced conditioned place preference (CPP) and amphetamine withdrawal anxiety-like behavior, both processes relevant to drug addiction/abuse. Intracerebroventricular (i.c.v.) injection of NPFF (5, 10, and 20 nmol) inhibited the expression of amphetamine CPP at the doses of 10 and 20 nmol. RF9, the NPFF receptors antagonist, reversed inhibitory effect of NPFF (20 nmol, i.c.v.) at the doses of 10 and 20 nmol and did not show any effect in amphetamine- and saline conditioned rats. Anxiety-like effect of amphetamine withdrawal was measured 24h after the last (14 days) amphetamine (2.5mg/kg, i.p.) treatment in the elevated plus-maze test. Amphetamine withdrawal decreased the percent of time spent by rats in the open arms and the percent of open arms entries. RF9 (5, 10, and 20 nmol, i.c.v.) significantly reversed these anxiety-like effects of amphetamine withdrawal and elevated the percent of time spent by rats in open arms at doses of 5 and 10 nmol, and the percent of open arms entries in all doses used. NPFF (20 nmol) pretreatment inhibited the effect of RF9 (10 nmol). Our results indicated that stimulation or inhibition of NPFF receptors decrease the expression of amphetamine CPP and amphetamine withdrawal anxiety, respectively. These findings may have implications for a better understanding of the processes involved in amphetamine dependence.

  6. Cocaine- and amphetamine-regulated transcript is a potent stimulator of GnRH and kisspeptin cells and may contribute to negative energy balance-induced reproductive inhibition in females.

    Science.gov (United States)

    True, Cadence; Verma, Saurabh; Grove, Kevin L; Smith, M Susan

    2013-08-01

    Cocaine- and amphetamine-regulated transcript (CART) is a hypothalamic neuropeptide implicated in both metabolic and reproductive regulation, raising the possibility that CART plays a role in reproductive inhibition during negative metabolic conditions. The current study characterized CART's regulatory influence on GnRH and kisspeptin (Kiss1) cells and determined the sensitivity of different CART populations to negative energy balance. CART fibers made close appositions to 60% of GnRH cells, with the majority of the fibers (>80%) originating from the arcuate nucleus (ARH) CART/pro-opiomelanocortin population. Electrophysiological recordings in GnRH-green fluorescent protein rats demonstrated that CART postsynaptically depolarizes GnRH cells. CART fibers from the ARH were also observed in close contact with Kiss1 cells in the ARH and anteroventral periventricular nucleus (AVPV). Recordings in Kiss1-GFP mice demonstrated CART also postsynaptically depolarizes ARH Kiss1 cells, suggesting CART may act directly and indirectly, via Kiss1 populations, to stimulate GnRH neurons. CART protein and mRNA levels were analyzed in 2 models of negative energy balance: caloric restriction (CR) and lactation. Both CART mRNA levels and the number of CART-immunoreactive cells were suppressed in the ARH during CR but not during lactation. AVPV CART mRNA was suppressed during CR, but not during lactation when there was a dramatic increase in CART-immunoreactive cells. These data suggest differing regulatory signals of CART between the models. In conclusion, both morphological and electrophysiological methods identify CART as a novel and potent stimulator of Kiss1 and GnRH neurons and suppression of CART expression during negative metabolic conditions could contribute to inhibition of the reproductive axis.

  7. Effects of a combination of 3,4-methylenedioxymeth amphetamine and caffeine on real time stimulated dopamine release in the rat striatum: Studies using fast cyclic voltammetry.

    Science.gov (United States)

    O'Connor, J J; O'Boyle, K M; Lowry, J P

    2017-08-24

    It is well documented that caffeine exacerbates the hyperthermia associated with acute exposure to 3,4-methylenedioxymethamphetamine (MDMA) in rats. Previous reports have also indicated that MDMA-related enhancement of dopamine release is exacerbated in the presence of caffeine. In the present study we have examined whether the effects of MDMA on real-time stimulated dopamine release, in the absence of uptake inhibition, are accentuated in the presence of caffeine. Isolated striatal slices from adult male Wistar rats were treated acutely with MDMA, caffeine, or a combination, and their effects on single and 5pulse stimulated dopamine release monitored using the technique of fast cyclic voltammetry. Caffeine at 10 or 100μM had no significant effect on single pulse stimulated dopamine release. However 100μM caffeine caused a significant peak increase in 5pulse stimulated dopamine release. Both 1 and 30μM MDMA gave rise to a significant increase in both single and 5-pulse dopamine release and reuptake. A combination of 100μM caffeine and 1 or 30μM MDMA did not significantly enhance the effects of MDMA on single or 5pulse dopamine release and reuptake when compared to that applied alone. Utilizing single action potential dependent dopamine release, these results do not demonstrate a caffeine-enhanced MDMA-induced dopamine release. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    OpenAIRE

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

    2016-01-01

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

  9. Mitochondria: key players in the neurotoxic effects of amphetamines.

    Science.gov (United States)

    Barbosa, Daniel José; Capela, João Paulo; Feio-Azevedo, Rita; Teixeira-Gomes, Armanda; Bastos, Maria de Lourdes; Carvalho, Félix

    2015-10-01

    Amphetamines are a class of psychotropic drugs with high abuse potential, as a result of their stimulant, euphoric, emphathogenic, entactogenic, and hallucinogenic properties. Although most amphetamines are synthetic drugs, of which methamphetamine, amphetamine, and 3,4-methylenedioxymethamphetamine ("ecstasy") represent well-recognized examples, the use of natural related compounds, namely cathinone and ephedrine, has been part of the history of humankind for thousands of years. Resulting from their amphiphilic nature, these drugs can easily cross the blood-brain barrier and elicit their well-known psychotropic effects. In the field of amphetamines' research, there is a general consensus that mitochondrial-dependent pathways can provide a major understanding concerning pathological processes underlying the neurotoxicity of these drugs. These events include alterations on tricarboxylic acid cycle's enzymes functioning, inhibition of mitochondrial electron transport chain's complexes, perturbations of mitochondrial clearance mechanisms, interference with mitochondrial dynamics, as well as oxidative modifications in mitochondrial macromolecules. Additionally, other studies indicate that amphetamines-induced neuronal toxicity is closely regulated by B cell lymphoma 2 superfamily of proteins with consequent activation of caspase-mediated downstream cell death pathway. Understanding the molecular mechanisms at mitochondrial level involved in amphetamines' neurotoxicity can help in defining target pathways or molecules mediating these effects, as well as in developing putative therapeutic approaches to prevent or treat the acute- or long-lasting neuropsychiatric complications seen in human abusers.

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  11. Repeated cognitive stimulation alleviates memory impairments in an Alzheimer's disease mouse model.

    Science.gov (United States)

    Martinez-Coria, Hilda; Yeung, Stephen T; Ager, Rahasson R; Rodriguez-Ortiz, Carlos J; Baglietto-Vargas, David; LaFerla, Frank M

    2015-08-01

    Alzheimer's disease is a neurodegenerative disease associated with progressive memory and cognitive decline. Previous studies have identified the benefits of cognitive enrichment on reducing disease pathology. Additionally, epidemiological and clinical data suggest that repeated exercise, and cognitive and social enrichment, can improve and/or delay the cognitive deficiencies associated with aging and neurodegenerative diseases. In the present study, 3xTg-AD mice were exposed to a rigorous training routine beginning at 3 months of age, which consisted of repeated training in the Morris water maze spatial recognition task every 3 months, ending at 18 months of age. At the conclusion of the final Morris water maze training session, animals subsequently underwent testing in another hippocampus-dependent spatial task, the Barnes maze task, and on the more cortical-dependent novel object recognition memory task. Our data show that periodic cognitive enrichment throughout aging, via multiple learning episodes in the Morris water maze task, can improve the memory performance of aged 3xTg-AD mice in a separate spatial recognition task, and in a preference memory task, when compared to naïve aged matched 3xTg-AD mice. Furthermore, we observed that the cognitive enrichment properties of Morris water maze exposer, was detectable in repeatedly trained animals as early as 6 months of age. These findings suggest early repeated cognitive enrichment can mitigate the diverse cognitive deficits observed in Alzheimer's disease.

  12. Pressure pain threshold changes after repeated mechano-nociceptive stimulation of the trapezius muscle: possible influence of previous pain experience

    DEFF Research Database (Denmark)

    Sjölund, Bengt H; Persson, Ann L

    2007-01-01

    We examined the relation between repeated noxious pressure over the trapezius muscle and changes in pressure pain thresholds (PPTs) in a before-after trial design. A conditioning series of 30 mechano-nociceptive stimuli was applied manually with a handheld algometer probe, and PPTs were measured...... who had given birth to 1 or several children (Ptested at a second session, a clear correlation of PPT reactions (r=0.527; Pmuscle in healthy females evokes moderate and temporary...... over 1 trapezius muscle (skin anaesthetized) in 27 healthy women before and after the intervention. With a mean stimulation rate of 0.40 Hz and a mean nociceptive stimulation intensity of 1.78 x Threshold, subjects were found to systematically react with a change in PPT, either a decrease...

  13. 苯丙胺类兴奋剂所致精神障碍者临床特征及危险因素分析%CLINICAL CHARACTERISTICS AND RISK FACTORS OF AMPHETAMINE-TYPE STIMULANT-INDUCED PSYCHOSIS

    Institute of Scientific and Technical Information of China (English)

    赵燕; 江海峰; 杜江; 任其欢; 李煦; 汪文文; 孙海明; 赵敏

    2014-01-01

    目的:探讨苯丙胺类兴奋剂(amphetamine-type stimulant,ATS)所致精神障碍患者的临床特征及危险因素.方法:采用横断面研究,收集了355例ATS滥用/依赖者的临床资料,其中符合ATS所致精神障碍者181例.结果:ATS滥用/依赖者以男性、低学历、无业及单身者居多.与无精神障碍的患者相比,有精神障碍组首次吸毒年龄较低、ATS依赖者和多药滥用者比例较高、吸毒剂量较高和过去1月中吸毒天数较多(P<0.01).多因素分析结果显示,存在ATS依赖的OR值为5.813(95% CI=3.655-10.231,P<0.01),多药滥用的OR值为2.262 (95%CI=1.309-3.727,P<0.01).结论:精神障碍患者的药物滥用程度较无精神障碍的患者更为严重.因此,在临床诊治中应重点预防药物滥用程度严重者的精神障碍的发生,尤其是依赖者及多药滥用者,以减少药物滥用所带来的损害.

  14. 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.

  15. Feasibility, repeatability, and safety of ultrasound-guided stimulation of the first cervical nerve at the alar foramen in horses.

    Science.gov (United States)

    Mespoulhès-Rivière, Céline; Brandenberger, Olivier; Rossignol, Fabrice; Robert, Céline; Perkins, Justin D; Marie, Jean-Paul; Ducharme, Norm

    2016-11-01

    OBJECTIVE To develop and assess the feasibility, repeatability, and safety of an ultrasound-guided technique to stimulate the first cervical nerve (FCN) at the level of the alar foramen of the atlas of horses. ANIMALS 4 equine cadavers and 6 clinically normal Standardbreds. PROCEDURES In each cadaver, the FCN pathway was determined by dissection, and any anastomosis between the first and second cervical nerves was identified. Subsequently, each of 6 live horses underwent a bilateral ultrasound-guided stimulation of the FCN at the alar foramen 3 times at 3-week intervals. After each procedure, horses were examined daily for 5 days. RESULTS In each cadaver, the FCN passed through the alar foramen; a communicating branch between the FCN and the accessory nerve and anastomoses between the ventral branches of the FCN and second cervical nerve were identified. The anastomoses were located in the upper third of the FCN pathway between the wing of the atlas and the nerve's entry in the omohyoideus muscle. Successful ultrasound-guided electrical stimulation was confirmed by twitching of the ipsilateral omohyoideus muscle in all 6 live horses; this finding was observed bilaterally during each of the 3 experimental sessions. No complications developed at the site of stimulation. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that ultrasound-guided stimulation of the FCN at the alar foramen appears to be a safe and straightforward procedure in horses. The procedure may have potential for use in horses with naturally occurring recurrent laryngeal neuropathy to assess reinnervation after FCN transplantation or nerve-muscle pedicle implantation in the cricoarytenoideus dorsalis muscle.

  16. Repeated transcranial magnetic stimulation prevents kindling-induced changes in electrophysiological properties of rat hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Shojaei, A; Semnanian, S; Janahmadi, M; Moradi-Chameh, H; Firoozabadi, S M; Mirnajafi-Zadeh, J

    2014-11-01

    The mechanisms underlying antiepileptic or antiepileptogenic effects of repeated transcranial magnetic stimulation (rTMS) are poorly understood. In this study, we investigated the effect of rTMS applied during rapid amygdala kindling on some electrophysiological properties of hippocampal CA1 pyramidal neurons. Male Wistar rats were kindled by daily electrical stimulation of the basolateral amygdala in a semi-rapid manner (12 stimulations/day) until they achieved stage-5 seizure. One group (kindled+rTMS (KrTMS)) of animals received rTMS (1Hz for 4min) 5min after termination of daily kindling stimulations. Twenty four hours following the last kindling stimulation electrophysiological properties of hippocampal CA1 pyramidal neurons were investigated using whole-cell patch-clamp technique. Amygdala kindling significantly depolarized the resting membrane potential and increased the input resistance, spontaneous firing activity, number of evoked spikes and half-width of the first evoked spike. Kindling also decreased the first-spike latency and amplitude significantly. Application of rTMS during kindling somehow prevented the development of seizures and protected CA1 pyramidal neurons of hippocampus against deleterious effect of kindling on both passive and active neuronal electrophysiological properties. Interestingly, application of rTMS alone enhanced the excitability of CA1 pyramidal neurons significantly. Based on the results of our study, it may be suggested that rTMS exerts its anticonvulsant effect, in part, through preventing the amygdala kindling-induced changes in electrophysiological properties of hippocampal CA1 pyramidal neurons. It seems that rTMS exerts protective effects on the neural circuits involved in spreading the seizures from the focus to other parts of the brain.

  17. Repeated stress-induced stimulation of catecholamine response is not followed by altered immune cell redistribution.

    Science.gov (United States)

    Imrich, Richard; Tibenska, Elena; Koska, Juraj; Ksinantova, Lucia; Kvetnansky, Richard; Bergendiova-Sedlackova, Katarina; Blazicek, Pavol; Vigas, Milan

    2004-06-01

    Stress response is considered an important factor in the modulation of immune function. Neuroendocrine hormones, including catecholamines, affect the process of immune cell redistribution, important for cell-mediated immunity. This longitudinal investigation was aimed at evaluating the effect of repeated stress-induced elevation of catecholamines on immune cell redistribution and expression of adhesive molecules. We assessed the responses of epinephrine (EPI), norepinephrine (NE), cortisol, changes in lymphocytes subpopulations, and percentages of CD11a+, CD11b+, and CD62L+ lymphocytes to a 20-min treadmill exercise of an intensity equal to 80% of the individual's Vo(2)max. The exercise was performed before and after 6 weeks of endurance training consisting of a 1-h run 4 times a week (ET) and after 5 days of bed rest (HDBR) in 10 healthy males. We did not observe any significant changes in the basal levels of EPI, NE, and cortisol in the plasma, nor in the immune parameters after ET and HDBR. The exercise test led to a significant (P <.001) elevation of EPI and NE levels after both ET and HDBR, a significant elevation (P <.01) of cortisol after HDBR, an increase in the absolute numbers of leukocytes, granulocytes, monocytes, CD3+, CD4+, CD8+, CD16+, CD19+ lymphocytes, percentage of CD11a+ and CD11b+ lymphocytes, and to a decrease of CD62L1 before, after ET, and after HDBR. We found comparable changes in all measured immune parameters after ET and HDBR. In conclusion, repeated stress-induced elevation of EPI and NE was not associated with an alteration in immune cell redistribution found in response to the single bout of exercise.

  18. Review article: amphetamines and related drugs of abuse.

    Science.gov (United States)

    Greene, Shaun L; Kerr, Fergus; Braitberg, George

    2008-10-01

    Acute amphetamine toxicity is a relatively common clinical scenario facing the Australasian emergency medicine physician. Rates of use in Australasia are amongst the highest in the world. Clinical effects are a consequence of peripheral and central adrenergic stimulation producing a sympathomimetic toxidrome and a spectrum of central nervous system effects. Assessment aims to detect the myriad of possible complications related to acute amphetamine exposure and to institute interventions to limit associated morbidity and mortality. Meticulous supportive care aided by judicial use of benzodiazepines forms the cornerstone of management. Beta blockers are contraindicated in managing cardiovascular complications. Agitation and hyperthermia must be treated aggressively. Discharge of non-admitted patients from the emergency department should only occur once physiological parameters and mental state have returned to normal. All patients should receive education regarding the dangers of amphetamine use.

  19. 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.

  20. Amphetamine positive urine toxicology screen secondary to atomoxetine.

    Science.gov (United States)

    Fenderson, Joshua L; Stratton, Amy N; Domingo, Jennifer S; Matthews, Gerald O; Tan, Christopher D

    2013-01-01

    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. Repeated sessions of transcranial direct current stimulation evaluation on fatigue and daytime sleepiness in Parkinson's disease.

    Science.gov (United States)

    Forogh, Bijan; Rafiei, Maryam; Arbabi, Amin; Motamed, Mohammad Reza; Madani, Seyed Pezhman; Sajadi, Simin

    2017-02-01

    Parkinson is a common and disabling disease that affects patient's and career's quality of life. Unfortunately, medications, such as dopaminergic and sedative-hypnotic drugs, as an effective treatment have unwilling side effects. Recently, Transcranial Direct Current Stimulation (tDCS) in conjunction with medication becomes popular as a complementary safe treatment and several studies have proved its effectiveness on controlling motor and specially non-motor aspects of Parkinson's disease. In this randomized double-blind parallel study, 23 patients with Parkinson's disease divided into two groups of real tDCS plus occupational therapy and sham tDCS plus occupational therapy and the effects of therapeutic sessions (eight sessions tDCS with 0.06 mA/cm(2) current, 20 min on dorsolateral prefrontal cortex) were evaluated on fatigue and daytime sleepiness just after therapeutic course and in 3-month follow-up. tDCS had a significant effect on fatigue and no effect on daytime sleepiness reduction in patients with Parkinson's disease. tDCS is an effective and safe complementary treatment on fatigue reduction in Parkinson's disease.

  2. A SURVEY ON THE EPIDEMIOLOGICAL CHARACTERISTICS OF AMPHETAMINE TYPE STIMULANTS IN SHANGHAI%上海地区苯丙胺类兴奋剂流行特征的调查

    Institute of Scientific and Technical Information of China (English)

    陈红; 江海峰; 杜江; 孙海明; 刘志民; 陆林; 赵敏

    2013-01-01

    目的:了解苯丙胺类兴奋剂(amphetamine type stimulants,ATS)滥用者的人群特点及滥用特征.方法:采用自制问卷,对上海地区339名ATS滥用者进行面谈,收集一般人口学资料和毒品滥用史.结果:调查结果显示:(1)ATS滥用者平均年龄为35.5 a±s 8.9 a,其中男性占65.2%,初中及以下文化占65.5%,已婚者(包括同居)占35.1%,无业者占49.6%;(2)滥用的主要物质是冰毒(95.9%),其滥用方式主要为烫吸(92.6%),平均滥用频率为5.0(18.0)次/月;(3)临床表现:滥用ATS后最常出现的症状为失眠(83.2%)、口干(77.9%)及兴奋(77.6%),滥用ATS后曾出现精神病性症状者占63.7%,其中最常见的为听幻觉(45.1%)、思维紊乱(39.8%)及妄想(38.1%).结论:上海地区苯丙胺类兴奋剂滥用者多数无稳定婚姻状况、文化程度较低,滥用后出现明显躯体及精神症状,产生严重不良后果.

  3. ANN expert system screening for illicit amphetamines using molecular descriptors

    Science.gov (United States)

    Gosav, S.; Praisler, M.; Dorohoi, D. O.

    2007-05-01

    The goal of this study was to develop and an artificial neural network (ANN) based on computed descriptors, which would be able to classify the molecular structures of potential illicit amphetamines and to derive their biological activity according to the similarity of their molecular structure with amphetamines of known toxicity. The system is necessary for testing new molecular structures for epidemiological, clinical, and forensic purposes. It was built using a database formed by 146 compounds representing drugs of abuse (mainly central stimulants, hallucinogens, sympathomimetic amines, narcotics and other potent analgesics), precursors, or derivatized counterparts. Their molecular structures were characterized by computing three types of descriptors: 38 constitutional descriptors (CDs), 69 topological descriptors (TDs) and 160 3D-MoRSE descriptors (3DDs). An ANN system was built for each category of variables. All three networks (CD-NN, TD-NN and 3DD-NN) were trained to distinguish between stimulant amphetamines, hallucinogenic amphetamines, and nonamphetamines. A selection of variables was performed when necessary. The efficiency with which each network identifies the class identity of an unknown sample was evaluated by calculating several figures of merit. The results of the comparative analysis are presented.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    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

    Corticostriatal signaling participates in sensitized responses to drugs of abuse, where short-term increases in dopamine availability provoke persistent, yet reversible, changes in glutamate release. Prior studies in mice show that amphetamine withdrawal promotes a chronic presynaptic depression in glutamate release, whereas an amphetamine challenge reverses this depression by potentiating corticostriatal activity in direct pathway medium spiny neurons. This synaptic plasticity promotes corticostriatal activity and locomotor sensitization through upstream changes in the activity of tonically active cholinergic interneurons (ChIs). We used a model of operant drug-taking behaviors, in which mice self-administered amphetamine through an in-dwelling catheter. Mice acquired amphetamine self-administration under fixed and increasing schedules of reinforcement. Following a period of abstinence, we determined whether nicotinic acetylcholine receptors modified drug-seeking behavior and associated alterations in ChI firing and corticostriatal activity. Mice responding to conditioned reinforcement showed reduced ChI and corticostriatal activity ex vivo, which paradoxically increased following an amphetamine challenge. Nicotine, in a concentration that increases Ca(2+) influx and desensitizes α4β2*-type nicotinic receptors, reduced amphetamine-seeking behaviors following abstinence and amphetamine-induced locomotor sensitization. Nicotine blocked the depression of ChI firing and corticostriatal activity and the potentiating response to an amphetamine challenge. Together, these results demonstrate that nicotine reduces reward-associated behaviors following repeated amphetamine and modifies the changes in ChIs firing and corticostriatal activity. By returning glutamatergic activity in amphetamine self-administering mice to a more stable and normalized state, nicotine limits the depression of striatal activity in withdrawal and the increase in activity following abstinence and

  6. Psychophysiological aspects of amphetamine-methamphetamine abuse.

    Science.gov (United States)

    Murray, J B

    1998-03-01

    Abuse of amphetamines-methamphetamines has increased worldwide. Profiles of abusers, effects of different methods of administration, and research on amphetamine psychosis are reviewed, along with research on psychophysiological mechanisms, addictive potential, and psychotherapeutic strategies.

  7. Impact of mGluR5 during amphetamine-induced hyperactivity and conditioned hyperactivity in differentially reared rats.

    Science.gov (United States)

    Gill, Margaret J; Arnold, Jennifer C; Cain, Mary E

    2012-05-01

    3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride (MTEP) is a metabotropic glutamate receptor 5 (mGluR5) antagonist that may alter drug sensitivity in differentially reared rats due to its involvement in the psychostimulant reward pathway and plasticity. The purpose of this study was to assess the effects of MTEP on acute amphetamine-induced hyperactivity, conditioned hyperactivity, and sensitization. Rats were reared in an enriched (EC), isolated (IC), or standard (SC) condition after which rats were either administered MTEP (1.0 mg/kg, ip) or saline prior to an acute (0.5 or 1.0 mg/kg, sc) or repeated (0.3 mg/kg, sc) amphetamine exposure. Rats undergoing repeated amphetamine exposure were administered MTEP prior to conditioned hyperactivity and sensitization tests. EC and SC rats administered with MTEP prior to acute amphetamine demonstrated attenuated amphetamine-induced locomotor activity compared to controls, while IC rats administered MTEP following repeated amphetamine exposure demonstrated attenuated amphetamine-induced locomotor activity. Interestingly, MTEP treatment only altered conditioned hyperactivity in EC rats, as MTEP pretreatment resulted in conditioned hyperactivity in EC rats while conditioned hyperactivity was not observed in EC rats pretreated with saline. Glutamatergic pathways are altered during differential rearing, which differentially alters the role of mGluR5 in EC, IC, and SC rats when administered psychostimulant acutely versus repeatedly. These findings suggest that differential rearing alters glutamatergic function, which reduces sensitivity to psychostimulants.

  8. The Ergogenic Effect of Amphetamine.

    Science.gov (United States)

    Zaretsky, Dmitry V; Brown, Mary Beth; Zaretskaia, Maria V; Durant, Pamela J; Rusyniak, Daniel E

    Amphetamine (Amp) increases exercise duration. It is thought to do so by masking fatigue, but there have been very few studies looking at the effect of amphetamine on VO2MAX and running economy. Furthermore, it is unknown if amphetamine's effect on exercise duration occurs in a warm environment. We conducted separate experiments in male Sprague-Dawley rats testing the effect of amphetamine on maximal oxygen consumption (VO2MAX) (n=12), running economy (n=12), and exercise duration (n=24) in a warm environment. For VO2MAX and running economy, rats were randomized to either amphetamine at 1 mg/kg (Amp-1) or 2 mg/kg (Amp-2). Animals served as their own controls in a crossover design with the administration order counter-balanced. To study the effect of amphetamine on exercise duration, we conducted run-to-exhaustion treadmill testing on rats in a 32°C environment following administration of Amp-1, Amp-2, or Saline. Compared to control, Amp-2 increased VO2MAX (by 861 ± 184 ml/kg/hr, p=0.005) and the time to VO2MAX (by 2.5 ± 0.8 min, p=0.03). Amp-1 had no effect on VO2MAX but increased the time to VO2MAX (by 1.7 ± 0.5 min, p=0.03). Neither dose improved running economy. In the warm, only rats in the Amp-1 group (+9.4 min, p=0.02) had an increased time to exhaustion. Compared to control (41.6 ± 0.3°C), both amphetamine doses had higher temperatures at exhaustion: Amp-1 (42.0 ± 0.2°C) and Amp-2 (42.1 ± 0.2°C). Our results suggest that ergogenic effect of amphetamine occurs by masking fatigue but this effect may be offset in the warm with higher doses.

  9. 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

  10. The neurotoxicity of amphetamines during the adolescent period.

    Science.gov (United States)

    Teixeira-Gomes, Armanda; Costa, Vera Marisa; Feio-Azevedo, Rita; Bastos, Maria de Lourdes; Carvalho, Félix; Capela, João Paulo

    2015-04-01

    Amphetamine-type psychostimulants (ATS), such as amphetamine (AMPH), 3,4-methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) are psychoactive substances widely abused, due to their powerful central nervous system (CNS) stimulation ability. Young people particularly use ATS as recreational drugs. Moreover, AMPH is used clinically, particularly for attention deficit hyperactivity disorder, and has the ability to cause structural and functional brain alterations. ATS are known to interact with monoamine transporter sites and easily diffuse across cellular membranes, attaining high levels in several tissues, particularly the brain. Strong evidence suggests that ATS induce neurotoxic effects, raising concerns about the consequences of drug abuse. Considering that many teenagers and young adults commonly use ATS, our main aim was to review the neurotoxic effects of amphetamines, namely AMPH, MDMA, and METH, in the adolescence period of experimental animals. Reports agree that adolescent animals are less susceptible than adult animals to the neurotoxic effects of amphetamines. The susceptibility to the neurotoxic effects of ATS seems roughly located in the early adolescent period of animals. Many authors report that the age of exposure to ATS is crucial for the neurotoxic outcome, showing that the stage of brain maturity has a strong importance. Moreover, recent studies have been undertaken in young adults and/or consumers during adolescence that clearly indicate brain or behavioural damage, arguing for long-term neurotoxic effects in humans. There is an urgent need for more studies during the adolescence period, in order to unveil the mechanisms and the brain dysfunctions promoted by ATS.

  11. 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.

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

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    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.

  13. The effects of d-govadine on conditioned place preference with d-amphetamine or food reward.

    Science.gov (United States)

    Nesbit, Maya O; Dias, Carine; Phillips, Anthony G

    2017-03-15

    Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB d-govadine on the acquisition, expression, extinction and reinstatement of d-amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of d-govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received d-govadine (0, 0.5 or 1.0mg/kg, i.p.) before a) each d-amphetamine injection during conditioning, b) expression of amphetamine-induced CPP, c) each extinction session, d) amphetamine-induced reinstatement of CPP, or e) placement into a compartment containing food during conditioning. Although d-govadine had no effect on acquisition of amphetamine CPP, treatment with d-govadine during acquisition dose-dependently extinguished a preference for the amphetamine-associated context more quickly than vehicle treatment. Moreover, d-govadine treatment facilitated the extinction of amphetamine CPP when given repeatedly throughout the extinction phase. Although the expression of amphetamine CPP was not affected by d-govadine administered prior to the expression test, amphetamine-induced reinstatement of CPP following an extinction period was blocked by d-govadine (1.0mg/kg). The intermediate dose of d-govadine blocked the acquisition of food CPP, whereas the high dose facilitated extinction of this preference as compared to vehicle-treated animals. Therefore, d-govadine attenuates the maintenance of conditioned associations between contextual stimuli and amphetamine or food reward, as well as amphetamine-induced reinstatement of drug seeking behaviour. As such, d-govadine may be a candidate for further development as a pharmacological treatment of psychostimulant drug dependence. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Physiological and behavioral effects of amphetamine in BACE1(-/-) mice.

    Science.gov (United States)

    Paredes, R Madelaine; Piccart, E; Navaira, E; Cruz, D; Javors, M A; Koek, W; Beckstead, M J; Walss-Bass, C

    2015-06-01

    β-Site APP-cleaving Enzyme 1 (BACE1) is a protease that has been linked to schizophrenia, a severe mental illness that is potentially characterized by enhanced dopamine (DA) release in the striatum. Here, we used acute amphetamine administration to stimulate neuronal activity and investigated the neurophysiological and locomotor-activity response in BACE1-deficient (BACE1(-/-) ) mice. We measured locomotor activity at baseline and after treatment with amphetamine (3.2 and 10 mg/kg). While baseline locomotor activity did not vary between groups, BACE1(-/-) mice exhibited reduced sensitivity to the locomotor-enhancing effects of amphetamine. Using high-performance liquid chromatography (HPLC) to measure DA and DA metabolites in the striatum, we found no significant differences in BACE1(-/-) compared with wild-type mice. To determine if DA neuron excitability is altered in BACE1(-/-) mice, we performed patch-clamp electrophysiology in putative DA neurons from brain slices that contained the substantia nigra. Pacemaker firing rate was slightly increased in slices from BACE1(-/-) mice. We next measured G protein-coupled potassium currents produced by activation of D2 autoreceptors, which strongly inhibit firing of these neurons. The maximal amplitude and decay times of D2 autoreceptor currents were not altered in BACE1(-/-) mice, indicating no change in D2 autoreceptor-sensitivity and DA transporter-mediated reuptake. However, amphetamine (30 µm)-induced potassium currents produced by efflux of DA were enhanced in BACE1(-/-) mice, perhaps indicating increased vesicular DA content in the midbrain. This suggests a plausible mechanism to explain the decreased sensitivity to amphetamine-induced locomotion, and provides evidence that decreased availability of BACE1 can produce persistent adaptations in the dopaminergic system.

  15. DESCRIPTION OF AND COUNTERMEASURES AGAINST AMPHETAMINE-TYPE STIMULANTS ABUSE IN HENAN PROVINCE 2010%2010年河南省苯丙胺类物质滥用者特征描述及防治对策

    Institute of Scientific and Technical Information of China (English)

    郭慧; 李文武; 张惠霞; 龚立雄; 王丽; 马雪皎; 夏旭东

    2012-01-01

    Objective:To understand the status of amphetamine - type stimulants (ATS) abuse and behavioral characteristics of ATS abusers by analyzing the monitoring report on drug abuse in Henan Province in 2010 and provide scientific information for strengthening special drug administration and establishing countermeasures against ATS abuse. Methods; A survey was conducted among drug abusers recruited by Henan local detoxification institutions in 2010 with the questionnaire designed by National Drug Surveillance Center and the data of ATS were analyzed. Results-. Altogether, 219 ATS cases were detected including 134 male( accounting for 61.2% )and 85 female(38.8% ) ;Methamphetamine was the main drug abused, accountiong for 84.5% (185 cases), and among them, the majority was male(59. 5% ) aged 35 a or lower(78. 5% ) , junior high school or lower(74. 0% ) , no job(72. 1% ) and single(68. 5% ). Curiosity was the main reason for ATS abuse. Drugs were mainly obtained from friends or peers. Smoking was the common route of drug abuse. The main place for using methamphetamine and MaGu pill was place of residence /lease,or hotel,and for "Ecstasy" use usually took place at night club/KTV . Conclusion:In Henan,the main ATS abused is methamphetamine. Young male, unmarried, with lower education level are the main body of ATS abuse. Appropriate prevention and intervention strategy should be conducted accordingly.%目的:了解河南省2010年监测报告中苯丙胺类物质滥用的流行病学特征,为加强特殊药品管理以及本地区政府相关部门制定防治措施提供依据.方法:采用国家药物滥用监测中心编制的《药物滥用监测调查表》,对2010年本地区戒毒机构的收戒人员进行问卷调查,将苯丙胺类物质滥用情况作为本文研究对象.结果:共调查苯丙胺类物质滥用者219例,其中男性134例(占61.2%),女性85例(占38.8%);在滥用的苯丙胺类物质中,冰毒滥用者最多,185例(占84.5

  16. 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.

  17. Adolescent mice are more vulnerable than adults to single injection-induced behavioral sensitization to amphetamine.

    Science.gov (United States)

    Kameda, Sonia R; Fukushiro, Daniela F; Trombin, Thaís F; Procópio-Souza, Roberta; Patti, Camilla L; Hollais, André W; Calzavara, Mariana B; Abílio, Vanessa C; Ribeiro, Rosana A; Tufik, Sergio; D'Almeida, Vânia; Frussa-Filho, Roberto

    2011-04-01

    Drug-induced behavioral sensitization in rodents has enhanced our understanding of why drugs acquire increasing motivational and incentive value. Compared to adults, human adolescents have accelerated dependence courses with shorter times from first exposure to dependence. We compared adolescent and adult mice in their ability to develop behavioral sensitization to amphetamine following a single injection. Adult (90-day-old) and adolescent (45-day-old) male Swiss mice received an acute intraperitoneal injection of saline or amphetamine (1.0, 2.0 or 4.0 mg/kg). Seven days later, half of the mice from the saline group received a second injection of saline. The remaining animals were challenged with 2.0 mg/kg amphetamine. Following all of the injections, mice were placed in activity chambers and locomotion was quantified for 45 min. The magnitude of both the acute and sensitized locomotor stimulatory effect of amphetamine was higher in the adolescent mice. Previous experience with the test environment inhibited the acute amphetamine stimulation in both adolescent and adult mice, but facilitated the detection of elevated spontaneous locomotion in adolescent animals. These results support the notion that the adolescent period is associated with an increased risk for development of drug abuse. Additionally, they indicate a complex interaction between the environmental novelty, adolescence and amphetamine.

  18. 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.

  19. Repeated cocaine enhances ventral hippocampal-stimulated dopamine efflux in the nucleus accumbens and alters ventral hippocampal NMDA receptor subunit expression.

    Science.gov (United States)

    Barr, Jeffrey L; Forster, Gina L; Unterwald, Ellen M

    2014-08-01

    Dopaminergic neurotransmission in the nucleus accumbens is important for various reward-related cognitive processes including reinforcement learning. Repeated cocaine enhances hippocampal synaptic plasticity, and phasic elevations of accumbal dopamine evoked by unconditioned stimuli are dependent on impulse flow from the ventral hippocampus. Therefore, sensitized hippocampal activity may be one mechanism by which drugs of abuse enhance limbic dopaminergic activity. In this study, in vivo microdialysis in freely moving adult male Sprague-Dawley rats was used to investigate the effect of repeated cocaine on ventral hippocampus-mediated dopaminergic transmission within the medial shell of the nucleus accumbens. Following seven daily injections of saline or cocaine (20 mg/kg, ip), unilateral infusion of N-methyl-d-aspartate (NMDA, 0.5 μg) into the ventral hippocampus transiently increased both motoric activity and ipsilateral dopamine efflux in the medial shell of the nucleus accumbens, and this effect was greater in rats that received repeated cocaine compared to controls that received repeated saline. In addition, repeated cocaine altered NMDA receptor subunit expression in the ventral hippocampus, reducing the NR2A : NR2B subunit ratio. Together, these results suggest that repeated exposure to cocaine produces maladaptive ventral hippocampal-nucleus accumbens communication, in part through changes in glutamate receptor composition. A behaviorally sensitizing regimen of cocaine (20 mg/kg, ip 7 days) also sensitized ventral hippocampus (hipp)-mediated dopaminergic transmission within the nucleus accumbens (Nac) to NMDA stimulation (bolts). This was associated with reduced ventral hippocampal NR2A:NR2B subunit ratio, suggesting that repeated exposure to cocaine produces changes in hippocampal NMDA receptor composition that lead to enhanced ventral hippocampus-nucleus accumbens communication.

  20. Amphetamine sensitization and amygdala kindling: pharmacological evaluation of catecholaminergic and cholinergic mechanisms.

    Science.gov (United States)

    Kirkby, R D; Kokkinidis, L

    1991-03-01

    Chronic pharmacological experiments were conducted to evaluate the relationship between sensitization induced by repeated administration of amphetamine (AMPH) and electrical stimulation of the amygdala. While AMPH withdrawal did not influence the kindling process, AMPH administered during the kindling procedure increased the rate at which seizures evolved, and under these conditions withdrawal from chronic AMPH further facilitated the propensity to kindle. Haloperidol (HAL) treatment failed to block the stimulant-induced increase in kindling acquisition indicating that changes in dopamine (DA) are not necessary for the AMPH/kindling synergism to develop. Scopolamine dose-dependently retarded kindling evolution irrespective of prior AMPH pretreatment also ruling out a cholinergic mechanism in the kindling sensitization. Subsequent experiments assessed the interactive effects of AMPH and desipramine (DMI) on the kindling process. Animals chronically exposed to AMPH and switched to DMI treatment during the kindling procedure kindled faster than control subjects. In addition, withdrawal from DMI preexposure advanced the AMPH-induced increase in kindling rate. These results were discussed in terms of the role of norepinephrine-mediated inhibition of the kindling process, and were related to drug-elicited alterations in beta-adrenergic receptor functioning. Taken together, these findings implicate the amygdala as an important structure in the development of non-DA forms of AMPH sensitization.

  1. Co-release of noradrenaline and dopamine in the cerebral cortex elicited by single train and repeated train stimulation of the locus coeruleus

    Directory of Open Access Journals (Sweden)

    Saba Pierluigi

    2005-05-01

    Full Text Available Abstract Background Previous studies by our group suggest that extracellular dopamine (DA and noradrenaline (NA may be co-released from noradrenergic nerve terminals in the cerebral cortex. We recently demonstrated that the concomitant release of DA and NA could be elicited in the cerebral cortex by electrical stimulation of the locus coeruleus (LC. This study analyses the effect of both single train and repeated electrical stimulation of LC on NA and DA release in the medial prefrontal cortex (mPFC, occipital cortex (Occ, and caudate nucleus. To rule out possible stressful effects of electrical stimulation, experiments were performed on chloral hydrate anaesthetised rats. Results Twenty min electrical stimulation of the LC, with burst type pattern of pulses, increased NA and DA both in the mPFC and in the Occ. NA in both cortices and DA in the mPFC returned to baseline within 20 min after the end of the stimulation period, while DA in the Occ reached a maximum increase during 20 min post-stimulation and remained higher than baseline values at 220 min post-stimulation. Local perfusion with tetrodotoxin (TTX, 10 μM markedly reduced baseline NA and DA in the mPFC and Occ and totally suppressed the effect of electrical stimulation in both areas. A sequence of five 20 min stimulations at 20 min intervals were delivered to the LC. Each stimulus increased NA to the same extent and duration as the first stimulus, whereas DA remained elevated at the time next stimulus was delivered, so that baseline DA progressively increased in the mPFC and Occ to reach about 130 and 200% the initial level, respectively. In the presence of the NA transport (NAT blocker desipramine (DMI, 100 μM, multiple LC stimulation still increased extracellular NA and DA levels. Electrical stimulation of the LC increased NA levels in the homolateral caudate nucleus, but failed to modify DA level. Conclusion The results confirm and extend that LC stimulation induces a concomitant

  2. Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/ΔFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus.

    Science.gov (United States)

    Giordano, Carmela; Vinet, Jonathan; Curia, Giulia; Biagini, Giuseppe

    2015-01-01

    Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs.

  3. Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/ΔFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus.

    Directory of Open Access Journals (Sweden)

    Carmela Giordano

    Full Text Available Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs.

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

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    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.

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

    Science.gov (United States)

    Branis, Natalia M; Wittlin, Steven D

    2015-01-01

    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.

  6. Amphetamine. Report Series 28, No. 1.

    Science.gov (United States)

    National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

    This report, prepared by the National Clearinghouse for Drug Abuse Information, presents substantial information on the use and abuse of the drug "family" known as amphetamines. A brief history of the drug is given, along with its basic pharmacology. The current medical uses for amphetamines include: (1) short-term treatment of obesity,…

  7. Amphetamine Abuse Related Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Archana Sinha

    2016-01-01

    Full Text Available Amphetamine abuse is a global problem. The cardiotoxic manifestations like acute myocardial infarction (AMI, heart failure, or arrhythmia related to misuse of amphetamine and its synthetic derivatives have been documented but are rather rare. Amphetamine-related AMI is even rarer. We report two cases of men who came to emergency department (ED with chest pain, palpitation, or seizure and were subsequently found to have myocardial infarction associated with the use of amphetamines. It is crucial that, with increase in amphetamine abuse, clinicians are aware of this potentially dire complication. Patients with low to intermediate risk for coronary artery disease with atypical presentation may benefit from obtaining detailed substance abuse history and urine drug screen if deemed necessary.

  8. Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine

    Science.gov (United States)

    Vicente-Rodríguez, Marta; Fernández-Calle, Rosalía; Gramage, Esther; Pérez-García, Carmen; Ramos, María P.

    2016-01-01

    Midkine (MK) is a cytokine that modulates amphetamine-induced striatal astrogliosis, suggesting a possible role of MK in neuroinflammation induced by amphetamine. To test this hypothesis, we studied astrogliosis and microglial response induced by amphetamine (10 mg/kg i.p. four times, every 2 h) in different brain areas of MK−/− mice and wild type (WT) mice. We found that amphetamine-induced microgliosis and astrocytosis are enhanced in the striatum of MK−/− mice in a region-specific manner. Surprisingly, LPS-induced astrogliosis in the striatum was blocked in MK−/− mice. Since striatal neuroinflammation induced by amphetamine-type stimulants correlates with the cognitive deficits induced by these drugs, we also tested the long-term effects of periadolescent amphetamine treatment (3 mg/kg i.p. daily for 10 days) in a memory task in MK−/− and WT mice. Significant deficits in the Y-maze test were only observed in amphetamine-pretreated MK−/− mice. The data demonstrate for the first time that MK is a novel modulator of neuroinflammation depending on the inflammatory stimulus and the brain area considered. The data indicate that MK limits amphetamine-induced striatal neuroinflammation. In addition, our data demonstrate that periadolescent amphetamine treatment in mice results in transient disruption of learning and memory processes in absence of endogenous MK. PMID:28044069

  9. Potential role of tyrosine hydroxylase in the loss of psychostimulant effect of amphetamine under conditions of impaired dopamine transporter activity.

    Science.gov (United States)

    Janenaite, Egle; Vengeliene, Valentina; Bespalov, Anton; Behl, Berthold

    2017-09-15

    Amphetamine and methylphenidate are known to have stimulatory effect in healthy subjects but not in humans with attention deficit hyperactivity disorder and in rodents with impaired dopamine transporter (DAT) function. This phenomenon is called the paradoxical calming effect of psychostimulants. It has been previously demonstrated that psychostimulants may regulate the enzymatic activity of tyrosine hydroxylase (TH). Hence, the objective of the present study was to determine whether the lack of activity-stimulating effects of amphetamine in hyperactive rats is associated with changes in TH activity. To model hyperactivity in rats, acute administration of DAT inhibitor GBR12909 was used. Changes in TH activity, assessed as L-DOPA accumulation and TH phosphorylation levels, were measured in amphetamine treated rats with or without pretreatment with GBR12909. Our results showed that amphetamine treatment alone increased locomotor activity in rats, whereas pretreatment of rats with GBR12909 counteracted this effect, a finding consistent with the paradoxical calming effect. GBR12909, while having no effect on its own, blocked amphetamine-induced elevation of TH activity in dorsal striatum and nucleus accumbens, measured as increased tissue L-DOPA concentration. However, the phosphorylation levels of TH were not affected by treatment with amphetamine, GBR12909 or the combination of both. Our findings indicate that other mechanisms than phosphorylation-regulated TH activity changes are responsible for the paradoxical calming effect of amphetamine under conditions of impaired DAT activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. [Schizophrenia and amphetamine dependence. A case report].

    Science.gov (United States)

    Dervaux, A; Krebs, M-O; Laqueille, X

    2005-01-01

    Whereas observations of psychotic disorders induced by amphetamines are common, few observations described the impact of chronic amphetamine abuse on schizophrenic patients. We report the case of a schizophrenic patient who presented with amphetamine dependence for several years, without other accompanying addiction. During his adolescence, Mr. X. gradually developed delusional beliefs of persecution and telepathy. He believed that the other pupils and teachers spoke about him in malicious terms. At the age of 23, Mr. X began to consume 60-100 mg/week of amphetamines orally. He consumed amphetamines during 7 years. The delusions, in particular the auditory hallucinations worsened after the use of amphetamines. Subsequently, he married and was declared unfit for national service due to the psychotic disorders. Mr. X received neuroleptic treatment with moderate effects on the psychotic symptoms. Between the age of 24 and 30, the patient presented persecutory, megalomanic and physical transformation beliefs, delusions of being controlled as well as auditory, somatic-tactile and visual hallucinations. At the age of 30, while he had stopped his consumption of amphetamines for 9 months, the patient, overwhelmed with the delusions, murdered his wife. He was sent in jail for 13 months, and subsequently hospitalized for one year in a high security psychiatric department and 7 years in our psychiatric department. The neuroleptic treatment was effective, particularly against the hallucinations. Following stabilisation, the symptomatology of the patient was marked by a disorganization syndrome, including prominent thought disorder, disorganized speech, associative loosening, frequent derailments and negative signs of schizophrenia, in particular affective flattening and blunting of emotional expression. When the patient was 43, a trial discharge was authorized owing to improvement of his condition. The neuroleptic treatment was switched with single-drug olanzapine therapy, 10

  11. Studies on the metabolism and the detectability of 4-methyl-amphetamine and its isomers 2-methyl-amphetamine and 3-methyl-amphetamine in rat urine using GC-MS and LC-(high-resolution)-MSn.

    Science.gov (United States)

    Welter, Jessica; Meyer, Markus R; Kavanagh, Pierce; Maurer, Hans H

    2014-03-01

    4-Methyl-amphetamine (1-(4-methylphenyl)propane-2-amine; 4-MA) and its isomers 2-methyl-amphetamine (2-MA) and 3-methyl-amphetamine (3-MA) belong to the group of amphetamine-type stimulants and of new psychoactive substances. Several studies showed similar potencies in releasing noradrenalin and dopamine, but higher potencies in releasing serotonin than amphetamine. In March 2013, the EU Council decided on an EU-wide control based on the European Monitoring Centre for Drugs and Drug Addiction risk assessment report documenting that 4-MA was sold as amphetamine on the illicit market and detected in several fatal cases. Therefore, 4-MA and its isomers should be covered by drug testing in clinical and forensic toxicology. The aims of the presented work were to study the metabolism and detectability of each isomer in urine samples. For metabolism studies, rat urine samples were isolated by solid-phase extraction without and after enzymatic cleavage of conjugates. The phase I metabolites were separated and identified after acetylation by gas chromatography-mass spectrometry (GC-MS) and/or liquid chromatography-high resolution-linear ion trap mass spectrometry (LC-HR-MS(n)) and the phase II metabolites by LC-HR-MS(n). From the identified phase I and II metabolites, the following main metabolic pathways were deduced: aromatic hydroxylation, hydroxylation of the phenylmethyl group followed by oxidation to the corresponding carboxylic acid, hydroxylation of the side chain, and glucuronidation and/or sulfation of the hydroxy and carboxy groups. CYP2D6 was involved in the aromatic hydroxylation. Finally, the intake of a commonly used dose of the MAs could be confirmed in rat urine using the authors' GC-MS and the LC-MS(n) standard urine screening approaches. Differentiation of the isomers to confirm the intake of a specific isomer was possible with an additional workup in rat urine.

  12. Differential effects of endomorphin-1 and -2 on amphetamine sensitization: neurochemical and behavioral aspects.

    Science.gov (United States)

    Chen, J C; Liang, K W; Huang, E Y

    2001-03-01

    Mu-opioid receptors are known to modulate mesolimbic dopaminergic activity in the ventral tegmental area via disinhibition of GABA-containing neurons. Recently, two novel tetrapeptides, endomorphin-1 and endomorphin-2, were identified in the mammalian brain and reported to have high binding affinities toward mu-opioid receptors. To determine if endomorphins would modulate the development of amphetamine sensitization, we administered endomorphins locally into the rat brain followed by behavioral and neurochemical examinations. The results indicate that rats pretreated with endomorphin-1 or -2 (5 microg per side for 7 days) in the ventral tegmental area developed locomotor sensitization to the challenge injection of amphetamine (1 mg/kg). On the other hand, when endomorphins were given in the lateral ventricle (20 microg for 5 days) of amphetamine-sensitized rats (5 mg/kg x 14 days) during the withdrawal period (w5-w9), neither peptide had a modulatory effect on locomotor sensitization. Biochemical analyses revealed that treatment with endomorphins in the ventral tegmental area significantly increased the levels of glutamate in the medial prefrontal cortex and ventral and dorsal striatum to levels comparable to those observed in the amphetamine-sensitized rats. In the same animals, endomorphins also caused decreases in the levels of serotonin and its metabolite, 5-hydroxyindoleacetic acid, in the medial prefrontal cortex. Interestingly, although there was no behavioral significance, endomorphin-1 treatment in the lateral ventricle of control and amphetamine-sensitized rats during withdrawal resulted in decreases of GABA, aspartate, dopamine, and its metabolite 3,4-dihydroxyphenylacetic acid in the ventral striatum. We conclude that endomorphins, by stimulating the mu-opioid receptors in the ventral tegmental area, could sensitize the behavioral response to amphetamine. The results also demonstrate that there are differential responses between endomorphin-1 and -2 on

  13. Frequency of false positive amphetamine screens due to bupropion using the Syva EMIT II immunoassay.

    Science.gov (United States)

    Casey, Erica R; Scott, Mitchell G; Tang, Schirin; Mullins, Michael E

    2011-06-01

    Bupropion is a commonly prescribed, monocyclic antidepressant often used as an aid for smoking cessation. Several case reports have described false positive amphetamine urine drug screens (UDS) associated with bupropion. We sought to determine whether false positive amphetamine UDS due to the use of bupropion would be a frequent occurrence. We conducted an IRB-approved, retrospective chart review of all emergency department patients who underwent UDS between 1 January 2006 and 31 July 2007. All urine samples were screened using Syva EMIT II Plus immunoassay reagents. All positive screens underwent confirmation by gas chromatography (GC). We reviewed the records of patients with positive amphetamine UDS. We documented prescription use of bupropion, other antidepressants, stimulants, antipsychotics, and anti-hypertensives. We recorded evidence of polysubstance abuse (PSA) as patients who had had a documented diagnosis or laboratory evidence of abuse of at least two substances (drugs or ethanol). Of 10,011 urine drug screens, 362 (3.6%) were positive for amphetamine. GC confirmed amphetamines in 234 (65%), but failed to confirm in 128 (35%). Among the 234 confirmed, records reflected use of bupropion in three (1.3%), other antidepressants in 38 (16%), antipsychotics in 17 (8%), and amphetamine in 50 (21%). Records indicated evidence of PSA in 55 (24%). Among the 128 which failed to confirm, records reflected prescription use of bupropion in 53 (41%). None whose drug screen failed to confirm had evidence of PSA. Therapeutic use of bupropion appears to be the most frequent cause of false positive urine drug screens for amphetamines in our population.

  14. Amphetamine and pseudoephedrine cross-tolerance measured by c-Fos protein expression in brains of chronically treated rats

    Directory of Open Access Journals (Sweden)

    Casalotti Stefano O

    2008-10-01

    Full Text Available Abstract Background Pseudoephedrine is a drug commonly prescribed as a nasal decongestant and bronchodilator and is also freely available in cold remedies and medications. The structural and pharmacological similarity of pseudoephedrine to amphetamine has led to evaluation of its psychomotor stimulant properties within the central nervous system. Previous investigations have shown that the acute responses to pseudoephedrine were similar to those of amphetamine and other psychostimulants. Results This study examined the effect of chronic administration of pseudoephedrine in rat nucleus accumbens and striatum and identified three further similarities to amphetamine. (i Chronic exposure to pseudoephedrine reduced the c-Fos response to acute pseudoephedrine treatment suggesting that pseudoephedrine induced tolerance in the animals. (ii In animals chronically treated with amphetamine or pseudoephedrine the acute c-Fos response to pseudoephedrine and amphetamine was reduced respectively as compared to naïve animals indicating cross-tolerance for the two drugs. (iiiThe known involvement of the dopamine system in the response to amphetamine and pseudoephedrine was further confirmed in this study by demonstrating that pseudoephedrine similarly to amphetamine, but with lower potency, inhibited [3H]dopamine uptake in synaptosomal preparations. Conclusion This work has demonstrated further similarities of the effect of pseudoephedrine to those of amphetamine in brain areas known to be associated with drug addiction. The most significant result presented here is the cross tolerance effect of amphetamine and psudoephedrine. This suggests that both drugs induce similar mechanisms of action in the brain. Further studies are required to establish whether despite its considerable lower potency, pseudoephedrine could pose health and addiction risks in humans similar to that of known psychostimulants.

  15. Choosing between GC FTIR and GC MS spectra for an efficient intelligent identification of illicit amphetamines

    Science.gov (United States)

    Gosav, S.; Dinica, R.; Praisler, M.

    2008-09-01

    In this paper we are presenting a comparative analysis between several expert systems built for the identification of illicit amphetamines based on their GC-FTIR and GC-MS spectra. The systems were built using Artificial Neural Networks (ANNs), and are dedicated to the recognition of amphetamines. Structure-activity relationships are incorporated into the knowledge base, allowing the systems to identify the amphetamines according to their toxicological activity (stimulant or hallucinogenic). The results show that GC-FTIR data are much more relevant for the efficiency of the expert systems, probably due to the fact that these spectra constitute a "fingerprint" of the molecular structures. We are also presenting a spectroscopic analysis in order to evaluate the relevance of each type of input variable (absorption and abundance) on which the recognition of an unknown sample is based.

  16. Prohibition or coffee shops: regulation of amphetamine and methylphenidate for enhancement use by healthy adults.

    Science.gov (United States)

    Dubljević, Veljko

    2013-01-01

    This article analyzes appropriate public policies for enhancement use of two most important stimulant drugs: Ritalin (methylphenidate) and Adderall (mixed amphetamine salts). The author argues that appropriate regulation of cognition enhancement drugs cannot be a result of a general discussion on cognitive enhancements as such, but has to be made on a case-by-case basis. Starting from the recently proposed taxation approach to cognition enhancement drugs, the author analyzes available, moderately permissive models of regulation. After a thorough analysis of relevant characteristics of methylphenidate and amphetamine, the author concludes that a moderately liberal permissive regulation of enhancement use by healthy adults might be appropriate for extended release forms of methylphenidate. However, due to their danger profile, amphetamine and instant release forms of methylphenidate should not be made readily available to healthy adults and would need to be prohibited.

  17. Optically stimulated luminescence sensitivity changes in quartz due to repeated use in single aliquot readout: Experiments and computer simulations

    DEFF Research Database (Denmark)

    McKeever, S.W.S.; Bøtter-Jensen, L.; Agersnap Larsen, N.

    1996-01-01

    As part of a study to examine sensitivity changes in single aliquot techniques using optically stimulated luminescence (OSL) a series of experiments has been conducted with single aliquots of natural quartz, and the data compared with the results of computer simulations of the type of processes...... believed to be occurring. The computer model used includes both shallow and deep ('hard-to-bleach') traps, OSL ('easy-to-bleach') traps, and radiative and non-radiative recombination centres. The model has previously been used successfully to account for sensitivity changes in quartz due to thermal...... trap and deep trap effects....

  18. 不伴精神症状的苯丙胺类兴奋剂依赖者家庭环境因素的初步分析%ANALYSIS OF THE FAMILY ENVIRONMENT IN AMPHETAMINE-TYPE STIMULANTS ADDICTS WITHOUT MENTAL SYMPTOMS

    Institute of Scientific and Technical Information of China (English)

    焦淑芬; 张昌勇

    2012-01-01

    Objective: To study the family environment of amphetamine - type stimulants addicts without mental symptoms. Methods: Sixty amphetamine -type stimulants addicts were tested with FES -CV. Results: Amphetamine -type stimulants addicts had higher score on cohesion, conflict, recreational and control than Chinese norms ( t = 2. 543, P =0.014, t =2.361, P =0.022, t = 2. 186, P = 0. 033,t =2.571, P =0.013) , and had lower score on expressiveness, achievement and intellectual than Chinese norms ( t= -2.213, P =0.031, t = -2.631, P =0.011, t = -2.268, P =0.027) . Positive correlations were found between cohesion and control ( r - 0.308, P< 0. 05 ) , expressiveness and organization r = 0. 430, P< 0. 01 ) , conflict and independence, intellectual, recreational, moral -religion, control( r =0. 271, P<0. 05, r =0. 512, P<0. 01, r =0. 493, P<0. 01, r =0. 425, P<0. 01, r = 0.413,P(0.01) , independence and intellectual, moral - religion, control ( r =0.372, P< 0. 01, r = 0. 370, P< 0. 01, r =0. 374, P< 0. 01 ) , intellectual and recreational, moral - religion, control( r = 0. 805, P<0. 01, r =0. 698, P<0. 01, r =0. 648, P<0. 01) , recreational and moral - religion, control( r = 0. 637, P< 0. 01, r = 0. 691, P< 0. 01 ) , control and moral - religion( r = 0. 501, P< 0. 01 ) . Negative correlations were found between control and organization ( r = - 0. 381, P< 0. 01 ) . Conclusion: These results indicated that amphetamine - type stimulants addicts without mental symptoms had special family environment, which was high cohesion, low expressiveness, high conflict, low achievement and intellectual, high recreational and control. Finally, we suggest that psychotherapy of comprehensive intervention with the correlation studies of the family environment will be helpful to recovery.%目的:初步分析不伴精神症状的苯丙胺类兴奋剂依赖者的家庭环境.方法:选择60例苯丙胺类兴奋剂依赖者自评中文版的家庭环境量表(FES-CV).结果:该类苯丙胺类兴奋

  19. 世界卫生组织西太区苯丙胺类中枢兴奋剂问题研讨会情况报告%Brief introduction of workshop on problems relating to the use of amphetamine-type stimulants in western pacific region

    Institute of Scientific and Technical Information of China (English)

    刘志民; 赵成正

    1998-01-01

    @@ 鉴于亚洲,特别是东南亚地区一些国家日益严重的苯丙胺类中枢兴奋剂(amphetamine-type stimulants,ATS)滥用问题,世界卫生组织(WHO)于1998年2月16日至20日在菲律宾首都马尼拉市WHO西太区办事处召开了ATS问题研讨会.来自澳大利亚、中国、日本、老挝、马来西亚、马里亚纳群岛、密克罗尼西亚、Palau群岛、菲律宾、新加坡、韩国和越南等12个国家和地区的20位代表,联合国国际毒品管制署(UNDCP)的代表,WHO西太区负责药物滥用事务的官员以及美国的观察员、协调员出席了会议.

  20. Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins

    Directory of Open Access Journals (Sweden)

    O'Donnell Michael A

    2007-11-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following repeated intravesical BCG therapy. Methods Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH. Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR was used to validate SSH-selected transcripts. Results Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH and representatives of two IFNγ-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5 and the p47GTPases (IIGTP1, IIGTP2, and TGTP. Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2, SPRR2G, GSTM5, and RSP 19. Conclusion Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially

  1. Differences between a single session and repeated sessions of 1 Hz TMS by double-cone coil prefrontal stimulation for the improvement of tinnitus.

    Science.gov (United States)

    Vanneste, Sven; De Ridder, Dirk

    2013-03-01

    Tinnitus related distress is associated with increased activity in the anterior cingulate cortex (ACC). In a recent study, it was demonstrated that a single session of low frequency prefrontal TMS using a double-cone coil (DCC) modulating the ACC (AC/DC TMS, anterior cingulate cortex targeted modulation by Double-Cone coil) yields a transient improvement in subjects with chronic tinnitus. An increasing number of studies demonstrated that repeated sessions of low frequency TMS to the temporoparietal area can significantly improve tinnitus complaints. Our aim is to determine the extent to which repeated sessions of AC/DC TMS can modulate tinnitus in comparison to a single session. Seventy-three tinnitus patients received a single (N = 46) or repetitive (N = 27) session(s) of TMS using a DCC placed over the prefrontal cortex. Our results indicate that both single sessions as well as multiple sessions (i.e. 8 sessions) of AC/DC TMS suppress both tinnitus distress (respectively 7.60% vs. 26.19%) and tinnitus intensity (respectively 7.12% vs. 19.60%) transiently. It was further shown that multiple sessions of AC/DC TMS generate a higher suppression effect in comparison to a single session of AC/DC TMS and that more patients responded to repeated sessions of 1 Hz stimulation in comparison to a single session. Our findings give further support to the fact that non-auditory areas are involved in tinnitus intensity and tinnitus distress and that more patients respond to repeated sessions with a higher suppression effect in comparison to patients who received a single session, suggesting that the approach of daily TMS sessions is relevant.

  2. Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex.

    Science.gov (United States)

    Fricke, K; Seeber, A A; Thirugnanasambandam, N; Paulus, W; Nitsche, M A; Rothwell, J C

    2011-03-01

    Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent "homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols.

  3. Serotonin (5-HT) precursor loading with 5-hydroxy-l-tryptophan (5-HTP) reduces locomotor activation produced by (+)-amphetamine in the rat.

    Science.gov (United States)

    Baumann, Michael H; Williams, Zakia; Zolkowska, Dorota; Rothman, Richard B

    2011-04-01

    Evidence suggests that increases in synaptic serotonin (5-HT) can reduce the stimulant properties of amphetamine-type drugs. Here we tested the hypothesis that administration of the 5-HT precursor 5-hydroxy-l-tryptophan (5-HTP), along with the peripheral decarboxylase inhibitor benserazide, would decrease locomotor effects of (+)-amphetamine. Drug treatments were administered to conscious male rats undergoing in vivo microdialysis in nucleus accumbens. During dialysis sampling, rats were housed in chambers equipped with photobeams to detect forward locomotion (i.e., ambulation) and repetitive movements (i.e., stereotypy). Extracellular concentrations of dopamine (DA) and 5-HT were measured by high-pressure liquid chromatography with electrochemical detection. 5-HTP (10 & 30 mg/kg, i.p.) plus benserazide (30 mg/kg, i.p.) caused dose-related increases in 5-HT but failed to alter other parameters. (+)-Amphetamine (0.3 & 1.0 mg/kg, i.p.) produced dose-related increases in DA, ambulation and stereotypy. Combined administration of 5-HTP and (+)-amphetamine evoked large elevations in extracellular DA and 5-HT, but caused significantly less ambulation than (+)-amphetamine alone (~50% reduction). Our results confirm that 5-HTP can decrease hyperactivity produced by (+)-amphetamine, even in the presence of elevations in dialysate DA. The data suggest that 5-HTP and (+)-amphetamine may be useful to broadly enhance monoamine function in the clinical setting, while reducing undesirable effects of (+)-amphetamine. Published by Elsevier Ireland Ltd.

  4. Serotonin (5-HT) Precursor Loading with 5-Hydroxy-L-tryptophan (5-HTP) Reduces Locomotor Activation Produced by (+)-Amphetamine in the Rat

    Science.gov (United States)

    Baumann, Michael H.; Williams, Zakia; Zolkowska, Dorota; Rothman, Richard B.

    2010-01-01

    Background Evidence suggests that increases in synaptic serotonin (5-HT) can reduce the stimulant properties of amphetamine-type drugs. Here we tested the hypothesis that administration of the 5-HT precursor 5-hydroxy-L-tryptophan (5-HTP), along with the peripheral decarboxylase inhibitor benserazide, would decrease locomotor effects of (+)-amphetamine. Methods Drug treatments were administered to conscious male rats undergoing in vivo microdialysis in nucleus accumbens. During dialysis sampling, rats were housed in chambers equipped with photobeams to detect forward locomotion (i.e., ambulation) and repetitive movements (i.e., stereotypy). Extracellular concentrations of dopamine (DA) and 5-HT were measured by high-pressure liquid chromatography with electrochemical detection. Results 5-HTP (10 & 30 mg/kg, i.p.) plus benserazide (30 mg/kg, i.p.) caused dose-related increases in 5-HT but failed to alter other parameters. (+)-Amphetamine (0.3 & 1.0 mg/kg, i.p.) produced dose-related increases in DA, ambulation and stereotypy. Combined administration of 5-HTP and (+)-amphetamine evoked large elevations in extracellular DA and 5-HT, but caused significantly less ambulation than (+)-amphetamine alone (~50% reduction). Conclusions Our results confirm that 5-HTP can decrease hyperactivity produced by (+)-amphetamine, even in the presence of elevations in dialysate DA. The data suggest that 5-HTP and (+)-amphetamine may be useful to broadly enhance monoamine function in the clinical setting, while reducing undesirable effects of (+)-amphetamine. PMID:21071157

  5. 苯丙胺类物质所致精神障碍患者的冲动性和认知决策能力研究%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; 王会; 赵晓丹; 徐芳芳; 郝伟

    2014-01-01

    目的 了解苯内胺类物质所致精神障碍患者的冲动性特点和认知决策能力,以及抗精神病药治疗前后的变化.方法 对100例苯丙胺所致精神障碍患者(病例组)进行抗精神病药治疗4周,采用Barratt冲动性量表(BIS)、Buss攻击性量表(BAS)和爱衙华博弈测验(IGT)于治疗前后分别评估其冲动攻击性和认知决策能力,并与100名年龄、性别相匹配的健康对照者(对照组)比较;采用单一样本t检验、独立样本t检验和重复测量方差分析对数据进行分析.结果 (1)病例组BIS、BAS治疗前总分显著高于对照组[(97.01 ±20.04)分比(62.56±11.59)分,t=13.45,P=0.000;(91.15±20.83)分比(57.78±13.48)分,t=14.88,P=0.000];病例组治疗后评分分别为(68.02±13.17)分和(61.78±13.38)分,较治疗前显著降低(t=11.95,P=0.000;t=11.86,P=0.000),但仍高于对照组(t =3.05,P=0.000;t=2.11,P=0.037);(2)病例组治疗后IGT评分优于治疗前(F=22.99,P=0.000),但治疗前后评分均差于对照组(F=23.51,P=0.000;F=24.15,P=0.000).结论 苯丙胺类物质所致精神障碍患者冲动攻击性较高,决策认知能力较差,抗精神病药治疗后可改善,但仍未达到无药物滥用者水平%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 disorder according to the Diagnostic and Statistical Manual of Mental Disorders,the fourth edition (DSM-Ⅳ) and 100 ATS-free healthy persons (control group) who matched with sex and age were recruited.The patient group was treated with antipsychotic drugs for 4 weeks,the impulsive-aggression and decision-making ability were assessed with the Barratt Impulsivity Scale (BIS),Barratt Aggressive Scale (BAS

  6. Greater sensitivity to novelty in rats is associated with increased motor impulsivity following repeated exposure to a stimulating environment: implications for the etiology of impulse control deficits.

    Science.gov (United States)

    Ferland, Jacqueline-Marie N; Zeeb, Fiona D; Yu, Katrina; Kaur, Sukhbir; Taves, Matthew D; Winstanley, Catharine A

    2014-12-01

    Heightened motor impulsivity and increased novelty-seeking commonly co-occur in psychiatric disorders, including drug addiction. However, the relationship between these two phenomena remains unclear. One-time tests of novelty sensitivity commonly used in preclinical experiments, such as the open-field or novel-object test, fail to capture the fact that novelty-seekers repeatedly experience novel, stimulating situations. The present study therefore investigated whether repeated exposure to a novel, stimulating environment (SE) altered impulsive action. Male Long-Evans rats were trained to perform the five-choice serial reaction time task (5CSRTT) which measures motor impulsivity in the form of premature responding as well as attention and motivation. Animals were then exposed to a novel SE (1 h/day for 16 days) immediately prior to the 5CSRTT. Significant increases in premature responding were observed in a subgroup of reactive animals termed high responders (HR-SE). These rats were not more impulsive at baseline, and levels of impulsivity normalised once exposure to the SE was discontinued. No other aspect of 5CSRTT performance was affected by the SE challenge. We also determined that HR-SE rats were hyperactive in a novel environment. Biochemical analyses revealed changes in gene and protein expression within the dorsal hippocampus of HR-SE rats, including decreases in mRNA encoding the dopamine D1 receptor and brain-derived neurotrophic factor. These results indicate a novel mechanism by which impulsivity and novelty-reactivity interact that may enhance addiction vulnerability synergistically. Furthermore, studying such context-induced impulsivity may provide insight into the process by which environmental load precipitates psychiatric symptoms in impulse control disorders.

  7. Tph2 gene deletion enhances amphetamine-induced hypermotility: effect of 5-HT restoration and role of striatal noradrenaline release.

    Science.gov (United States)

    Carli, Mirjana; Kostoula, Chrysaugi; Sacchetti, Giuseppina; Mainolfi, Pierangela; Anastasia, Alessia; Villani, Claudia; Invernizzi, Roberto William

    2015-11-01

    Variants of tryptophan hydroxylase-2 (Tph2), the gene encoding enzyme responsible for the synthesis of brain serotonin (5-HT), have been associated with neuropsychiatric disorders, substance abuse and addiction. This study assessed the effect of Tph2 gene deletion on motor behavior and found that motor activity induced by 2.5 and 5 mg/kg amphetamine was enhanced in Tph2(-/-) mice. Using the in vivo microdialysis technique we found that the ability of amphetamine to stimulate noradrenaline (NA) release in the striatum was reduced by about 50% in Tph2(-/-) mice while the release of dopamine (DA) was not affected. Tph2 deletion did not affect the release of NA and DA in the prefrontal cortex. The role of endogenous 5-HT in enhancing the effect of amphetamine was confirmed showing that treatment with the 5-HT precursor 5-hydroxytryptophan (10 mg/kg) restored tissue and extracellular levels of brain 5-HT and the effects of amphetamine on striatal NA release and motor activity in Tph2(-/-) mice. Treatment with the NA precursor dihydroxyphenylserine (400 mg/kg) was sufficient to restore the effect of amphetamine on striatal NA release and motor activity in Tph2(-/-) mice. These findings indicate that amphetamine-induced hyperactivity is attenuated by endogenous 5-HT through the inhibition of striatal NA release. Tph2(-/-) mice may be a useful preclinical model to assess the role of 5-HT-dependent mechanisms in the action of psychostimulants. Acute sensitivity to the motor effects of amphetamine has been associated to increased risk of psychostimulant abuse. Here, we show that deletion of Tph2, the gene responsible for brain 5-HT synthesis, enhances the motor effect of amphetamine in mice through the inhibition of striatal NA release. This suggests that Tph2(-/-) mice is a useful preclinical model to assess the role of 5-HT-dependent mechanisms in psychostimulants action. Tph2, tryptophan hydroxylase-2.

  8. Small volume liquid extraction of amphetamines in saliva.

    Science.gov (United States)

    Meng, Pinjia; Wang, Yanyan

    2010-04-15

    The present study introduced a procedure of small volume liquid extraction of amphetamines, including amphetamine (AM); methamphetamine (MA); 3,4-methylenedioxyamphetamine (MDA); 3,4-methylenemethamphtamine (MDMA), in saliva. Extraction efficiencies were compared between the conventional volume liquid phase extraction (LPE) and the small volume one, in which amphetamine abusers, and was proven to be practical for detecting trace amounts of amphetamines in saliva.

  9. Comparative Effects of Methylphenidate and Mixed Salts Amphetamine on Height and Weight in Children with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Pliszka, Steven R.; Matthews, Thomas L.; Braslow, Kenneth J.; Watson, Melissa A.

    2006-01-01

    Objective: To determine whether methylphenidate (MPH) and mixed salts amphetamine (MSA) have different effects on growth in children with attention-deficit/hyperactivity disorder. Method: Patients treated for at least 1 year with MPH or MSA were identified. A linear regression was performed to determine the effect of stimulant type, patient…

  10. 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.

  11. Electrochemical oxidation of amphetamine-like drugs and application to electroanalysis of ecstasy in human serum.

    Science.gov (United States)

    Garrido, E M P J; Garrido, J M P J; Milhazes, N; Borges, F; Oliveira-Brett, A M

    2010-08-01

    Amphetamine and amphetamine-like drugs are popular recreational drugs of abuse because they are powerful stimulants of the central nervous system. Due to a dramatic increase in the abuse of methylenedioxylated derivatives, individually and/or in a mixture, and to the incoherent and contradictory interpretation of the electrochemical data available on this subject, a comprehensive study of the redox properties of amphetamine-like drugs was accomplished. The oxidative behaviour of amphetamine (A), methamphetamine (MA), methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) was studied in different buffer systems by cyclic, differential pulse and square-wave voltammetry using a glassy carbon electrode. A quantitative electroanalytical method was developed and successfully applied to the determination of MDMA in seized samples and in human serum. Validation parameters, such as sensitivity, precision and accuracy, were evaluated. The results found using the developed electroanalytical methodology enabled to gather some information about the content and amount of MDMA present in ecstasy tablets found in Portugal. Moreover, the data found in this study outlook the possibility of using the voltammetric methods to investigate the potential harmful effects of interaction between drugs such as MDMA and methamphetamine and other substances often used together in ecstasy tablets.

  12. Second time around:Corticospinal responses following repeated sports-related concussions within the same season. A transcranial magnetic stimulation study

    Institute of Scientific and Technical Information of China (English)

    Alan J Pearce; Daniel T Corp; Charlotte B Davies; Brendan P Major; Jerome J Maller

    2014-01-01

    Objective:To investigate the degree of neurophysiological and cognitive performance changes resulting from repeat concussions sustained in a single season ofAustralianRules football. Methods:Three amateur football players were recruited after sustainingtwo concussions during a single season of playing.Each player was assessed at multiple time points by transcranial magnetic stimulation(TMS) and electromyography, as well as tested for fine motor and cognitive performance after each concussion.Results:In all three cases, concussions resulted in reduction in fine dexterity and visuomotor reaction time, cognitive attention performance and increase in intracortical inhibition fromTMS.No changes in performance orTMS outcomes were found as a result of the order of the concussions.However, changes observed were dependent on the severity of the concussion.Conclusions:This multiple-case study has demonstrated that concussion result in increased intracortical inhibition and reduction in cognitive and motor performance. Further,TMS, in conjunction with tests of cognitive and motor performance, can be useful as a prognostic technique in assessing recovery from acute concussion injury.

  13. Neurotoxicity of drugs of abuse--the case of methylenedioxyamphetamines (MDMA, ecstasy), and amphetamines.

    Science.gov (United States)

    Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    showed that M(5) receptor knockout (M (5) (-/-) ) mice are less sensitive to the reinforcing properties of addictive drugs. MATERIALS AND METHODS: Here, we investigate the role of M(5) receptors in the effects of amphetamine and cocaine on locomotor activity, locomotor sensitization, and dopamine release...... using M (5) (-/-) mice backcrossed to the C57BL/6NTac strain. STATISTICAL ANALYSES: Sensitization of the locomotor response is considered a model for chronic adaptations to repeated substance exposure, which might be related to drug craving and relapse. The effects of amphetamine on locomotor activity......-induced hyperactivity and dopamine release as well as amphetamine sensitization are enhanced in mice lacking the M(5) receptor. These results support the concept that the M(5) receptor modulates effects of addictive drugs....

  15. 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.

  16. Amphetamines in the Treatment of Hyperkinetic Children

    Science.gov (United States)

    Grinspoon, Lester; Singer, Susan B.

    1973-01-01

    Article is a literature review, but a literature review with definite policy implications. It concerns the widespread use of amphetamines in the nation's schools to control a syndrome which doctors and medical researchers call "hyperkinetic behavior disorder," or "minimal brain dysfunction," and which teachers and parents know as "hyperactivity".…

  17. Monoamine transporter and receptor interaction profiles of novel psychoactive substances: para-halogenated amphetamines and pyrovalerone cathinones.

    Science.gov (United States)

    Rickli, Anna; Hoener, Marius C; Liechti, Matthias E

    2015-03-01

    The pharmacology of novel psychoactive substances is mostly unknown. We evaluated the transporter and receptor interaction profiles of a series of para-(4)-substituted amphetamines and pyrovalerone cathinones. We tested the potency of these compounds to inhibit the norepinephrine (NE), dopamine (DA), and serotonin (5-HT) transporters (NET, DAT, and SERT, respectively) using human embryonic kidney 293 cells that express the respective human transporters. We also tested the substance-induced efflux of NE, DA, and 5-HT from monoamine-loaded cells, binding affinities to monoamine receptors, and 5-HT2B receptor activation. Para-(4)-substituted amphetamines, including 4-methylmethcathinone (mephedrone), 4-ethylmethcathinone, 4-fluoroamphetamine, 4-fluoromethamphetamine, 4-fluoromethcatinone (flephedrone), and 4-bromomethcathinone, were relatively more serotonergic (lower DAT:SERT ratio) compared with their analogs amphetamine, methamphetamine, and methcathinone. The 4-methyl, 4-ethyl, and 4-bromo groups resulted in enhanced serotonergic properties compared with the 4-fluoro group. The para-substituted amphetamines released NE and DA. 4-Fluoramphetamine, 4-flouromethamphetamine, 4-methylmethcathinone, and 4-ethylmethcathinone also released 5-HT similarly to 3,4-methylenedioxymethamphetamine. The pyrovalerone cathinones 3,4-methylenedioxypyrovalerone, pyrovalerone, α-pyrrolidinovalerophenone, 3,4-methylenedioxy-α-pyrrolidinopropiophenone, and 3,4-methylenedioxy-α-pyrrolidinobutiophenone potently inhibited the NET and DAT but not the SERT. Naphyrone was the only pyrovalerone that also inhibited the SERT. The pyrovalerone cathinones did not release monoamines. Most of the para-substituted amphetamines exhibited affinity for the 5-HT2A receptor but no relevant activation of the 5-HT2B receptor. All the cathinones exhibited reduced trace amine-associated receptor 1 binding compared with the non-β-keto-amphetamines. In conclusion, para-substituted amphetamines exhibited

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

    Directory of Open Access Journals (Sweden)

    Andrew John Dudley Nelson

    2013-05-01

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

  19. 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...

  20. High fat diet augments amphetamine sensitization in mice: Role of feeding pattern, obesity, and dopamine terminal changes.

    Science.gov (United States)

    Fordahl, Steve C; Locke, Jason L; Jones, Sara R

    2016-10-01

    High fat (HF) diet-induced obesity has been shown to augment behavioral responses to psychostimulants that target the dopamine system. The purpose of this study was to characterize dopamine terminal changes induced by a HF diet that correspond with enhanced locomotor sensitization to amphetamine. C57BL/6J mice had limited (2hr 3 d/week) or extended (24 h 7 d/week) access to a HF diet or standard chow for six weeks. Mice were then repeatedly exposed to amphetamine (AMPH), and their locomotor responses to an amphetamine challenge were measured. Fast scan cyclic voltammetry was used to identify changes in dopamine terminal function after AMPH exposure. Exposure to a HF diet reduced dopamine uptake and increased locomotor responses to acute, high-dose AMPH administration compared to chow fed mice. Microdialysis showed elevated extracellular dopamine in the nucleus accumbens (NAc) coincided with enhanced locomotion after acute AMPH in HF-fed mice. All mice exhibited locomotor sensitization to amphetamine, but both extended and limited access to a HF diet augmented this response. Neither HF-fed group showed the robust amphetamine sensitization-induced increases in dopamine release, reuptake, and amphetamine potency observed in chow fed animals. However, the potency of amphetamine as an uptake inhibitor was significantly elevated after sensitization in mice with extended (but not limited) access to HF. Conversely, after amphetamine sensitization, mice with limited (but not extended) access to HF displayed reduced autoreceptor sensitivity to the D2/D3 agonist quinpirole. Additionally, we observed reduced membrane dopamine transporter (DAT) levels after HF, and a shift in DAT localization to the cytosol was detected with limited access to HF. This study showed that different patterns of HF exposure produced distinct dopamine terminal adaptations to repeated AMPH, which differed from chow fed mice, and enhanced sensitization to AMPH. Locomotor sensitization in chow fed

  1. The Nonmedical Use of Amphetamines among the College Age Group: Recent Research concerning Epidemiology and Toxicity.

    Science.gov (United States)

    Nicholi, Armand M., Jr.

    1984-01-01

    Amphetamines have a significant role in nontherapeutic drug use by college students. A brief history of amphetamine use by college students is presented. Considerable data implicate amphetamines in producing serious psychological and biological adverse effects. (Author/DF)

  2. Calcium channel antagonists suppress cross-tolerance to the anxiogenic effects of D-amphetamine and nicotine in the mouse elevated plus maze test.

    Science.gov (United States)

    Biala, Grazyna; Kruk, Marta

    2008-01-01

    The purpose of the current experiments was to examine the anxiety-related effects of repeated amphetamine and nicotine administration using the mouse elevated plus maze (EPM). d-amphetamine was administered daily for 8 days (2 mg/kg, i.p.). On the 9th day, mice were challenged with amphetamine (2 mg/kg, i.p.) or nicotine (0.1 mg/kg, s.c.), and were tested 30 min after this last injection. Additionally, a distinct group of mice was pretreated with nicotine (0.1 mg/kg, s.c., 6 days). These mice were subjected to nicotine (0.1 mg/kg, s.c.) or amphetamine (2 mg/kg, i.p.) challenge on the seventh day to see if full crossover effects developed after the pretreatment of both psychostimulant drugs. Moreover, the L-type voltage-dependent calcium channel antagonists nimodipine (5 and 10 mg/kg, i.p.), flunarizine (5 and 10 mg/kg, i.p.), verapamil (5 and 10 mg/kg, i.p.) and diltiazem (5 and 10 mg/kg, i.p.) were injected prior to each injection of chronic d-amphetamine or nicotine. We observed cross-tolerance to the anxiogenic effects of d-amphetamine and nicotine that was blunted by a pretreatment with calcium channel blockers. Overall our findings imply that similar neural calcium-dependent mechanisms are involved in the anxiety-related responses to chronic amphetamine and nicotine injections. As anxiety seems to be an important factor for the development of psychostimulant dependence, the L-type VDCC antagonists can offer an interesting approach for the pharmacotherapy of addiction, including amphetamine and/or nicotine dependence.

  3. Report of leucine-rich repeats (LRRs) from Scylla serrata: Ontogeny, molecular cloning, characterization and expression analysis following ligand stimulation, and upon bacterial and viral infections.

    Science.gov (United States)

    Vidya, R; Makesh, M; Purushothaman, C S; Chaudhari, A; Gireesh-Babu, P; Rajendran, K V

    2016-09-15

    Leucine-rich repeat (LRR) proteins are present in all living organisms, and their participation in signal transduction and defense mechanisms has been elucidated in humans and mosquitoes. LRRs possibly involve in protein-protein interactions also and show differential expression pattern upon challenge with pathogens. In the present study, a new LRR gene was identified in mud crab, Scylla serrata. LRR gene mRNA levels in different developmental stages and various tissues of S. serrata were analysed. Further, the response of the gene against different ligands, Gram-negative bacterium, and white spot syndrome virus (WSSV) was investigated in vitro and in vivo. Full-length cDNA sequence of S. serrata LRR (SsLRR) was found to be 2290 nucleotide long with an open reading frame of 1893bp. SsLRR encodes for a protein containing 630 deduced amino acids with 17 conserved LRR domains and exhibits significant similarity with crustacean LRRs so that these could be clustered into a branch in the phylogenetic tree. SsLRR mRNA transcripts were detected in all the developmental stages (egg, Zoea1-5, megalopa and crab instar), haemocytes and various tissues such as, stomach, gill, muscle, hepatopancreas, hematopoietic organ, heart, epithelial layer and testis by reverse-transcriptase PCR. SsLRR transcripts in cultured haemocytes showed a 2-fold increase in expression at 1.5 and 12h upon Poly I:C induction. WSSV challenge resulted in significant early up-regulation at 3h in-vitro and late up-regulation at 72h in-vivo. Peptidoglycan (PGN)-induction resulted in marginal up-regulation of SsLRR at timepoints, 6, 12 and 24h (fold change below 1.5) and no significant change in the expression at early timepoints. LPS-stimulation, on the other hand, showed either down-regulation or normal level of expression at all timepoints. However, a delayed 5-fold up-regulation was observed in vivo against Vibrio parahaemolyticus infection at 72hpi. The constitutive expression of the LRR gene in all the

  4. The role of BDNF/TrkB signaling in acute amphetamine-induced locomotor activity and opioid peptide gene expression in the rat dorsal striatum

    Directory of Open Access Journals (Sweden)

    Jacqueline F McGinty

    2011-07-01

    Full Text Available Exposure to psychostimulants increases brain-derived neurotrophic factor (BDNF mRNA and protein levels in the cerebral cortex and subcortical structures. Because BDNF is co-localized with dopamine and glutamate in afferents to the striatum of rats, it may be co-released with those neurotransmitters upon stimulation. Further, there may be an interaction between the intracellular signaling cascades activated by dopamine, glutamate, and TrkB receptors in medium spiny striatal neurons. In the present study, the effect of acute amphetamine administration on TrkB phosphorylation (p-TrkB, as an indirect indicator of activation, and striatal gene expression, was evaluated. In Experiment 1, 15 minutes or 2 hours after a single saline or amphetamine (2.5 mg/kg, i.p. injection, the caudate-putamen (CPu, nucleus accumbens (NAc, and dorsomedial prefrontal cortex (dmPFC were extracted and processed for phospho (p-TrkB immunoreactivity. Immunoprecipitation analyses indicated that neither the tyrosine phosphorylation (p-Tyr or autophosphorylation sites of TrkB (706 were changed in NAc, CPu, or dmPFC 15 min after amphetamine administration. In contrast, p-Tyr and the PLCγ phosphorylation site of TrkB (816 were increased in the NAc and CPu 2 hrs after amphetamine. In Experiment 2, intra-striatal infusion of the tyrosine kinase inhibitor, K252a, increased amphetamine-induced vertical activity but not total distance traveled. In addition, K252a inhibited amphetamine -induced preprodynorphin, but not preproenkephalin, mRNA expression in the striatum. These data indicate that acute amphetamine administration induces p-TrkB activation and signaling in a time- and brain region-dependent manner and that TrkB/BDNF signaling plays an important role in amphetamine-induced behavior and striatal gene expression.

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

    Science.gov (United States)

    Meyer, Andrew C; Bardo, Michael T

    2015-07-01

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

  6. Central nervous system stimulants.

    Science.gov (United States)

    George, A J

    2000-03-01

    Three major types of CNS stimulant are currently abused in sport: amphetamine, cocaine and caffeine. Each drug type has its own characteristic mechanism of action on CNS neurones and their associated receptors and nerve terminals. Amphetamine is widely abused in sports requiring intense anaerobic exercise where it prolongs the tolerance to anaerobic metabolism. It is addictive, and chronic abuse causes marked behavioural change and sometimes psychosis. Major sports abusing amphetamine are cycling, American football, ice-hockey and baseball. Cocaine increases tolerance to intense exercise, yet most of its chronic effects on energy metabolism are negative. Its greatest effects seem to be as a central stimulant and the enhancement of short-term anaerobic exercise. It is highly addictive and can cause cerebral and cardiovascular fatalities. Caffeine enhances fatty acid metabolism leading to glucose conservation, which appears to benefit long-distance endurance events such as skiing. Caffeine is also addictive, and chronic abuse can lead to cardiac damage. Social abuse of each of the three drugs is often difficult to distinguish from their abuse in sport.

  7. 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

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

    Science.gov (United States)

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

    2014-01-01

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

  9. HIV risks for women drug injectors: heroin and amphetamine users compared.

    Science.gov (United States)

    Klee, H

    1993-08-01

    The incidence of HIV infection among women in Europe and the US is growing rapidly. Women who inject drugs are particularly vulnerable--they may acquire the infection through sharing injecting equipment and through sexual contact with an infected male. Opioids and stimulants are reputed to have different effects upon sexual activity and a sex life enhanced by drugs may increase the risk further. In the context of two larger studies of HIV-related risk behaviours among opioid and amphetamine users in the North West of England, the sexual behaviour and sharing of two groups of female injectors were compared, one whose primary use was heroin, the other amphetamine. Reported incidence of sharing was similar and high. Marked differences were observed in sexual behaviour, amphetamine injectors reporting greater interest in sex and greater frequency of intercourse. However, more of them perceived their personal risk to infection through unprotected sex as negligible. Over 80% in both groups had engaged in unprotected sex in the 6 months prior to interview. Women injectors tend to have injecting partners--more research is needed if health education strategies are to be devised that will protect them.

  10. 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.

  11. Rapid GC-MS confirmation of amphetamines in urine by extractive acylation.

    Science.gov (United States)

    Marais, Adriaan A S; Laurens, Johannes B

    2009-01-10

    Amphetamine and related derivatives are widely abused central- and psychostimulants. Detection of certain derivatives, such as methcathinone, by commonly available immunoassay screening techniques is insufficient. Multi-analyte confirmations for amphetamine type stimulants are therefore required, but traditional gas chromatography-mass spectrometry methods necessitate lengthy analytical procedures with prolonged sample turn-around times. A validated rapid GC-MS assay for urinary confirmation of amphetamine, methamphetamine, methcathinone, ephedrine, norephedrine, methylenedioxyamphetamine, methylenedioxymethamphetamine, methylenedioxyethylamphetamine and N-methyl-1-(3,4 methylenedioxyphenyl)-2-butanamine is reported. The method entailed in situ derivatization of urine specimens by extractive acylation with pentafluoropropionic anhydride, followed by rapid chromatography on a microbore capillary column. Analytes were separated in less than 3 min and quantified simultaneously by selected-ion monitoring using stable isotope substituted internal standards. The total instrument cycle-time was 6 min per sample. The limits of detection were between 1.5 ng/mL and 6.25 ng/mL for the various analytes. Intermediate precision and accuracy were in the range of 6.3-13.8% and 90.5-107.3% for the respective analytes at the lower limit of quantitation, and between 5.8-12.6% and 95.4-103.1% for the high control. Long-term storage of methcathinone positive specimens at -20 degrees C proved insufficient stability of this analyte. The proposed assay is precise and accurate for confirmation of amphetamine and derivatives in urine. The complementary approach of extractive-derivatization and fast GC-MS analysis is especially applicable in routine clinical settings where reduced sample turn-around times are required. Further investigation of cathinone as a possible metabolite of methcathinone is warranted, based on results from analyzed authentic urine samples.

  12. Requirement for the POZ/BTB protein NAC1 in acute but not chronic psychomotor stimulant response.

    Science.gov (United States)

    Mackler, Scott; Pacchioni, Alejandra; Degnan, Ryan; Homan, Ying; Conti, Alana C; Kalivas, Peter; Blendy, Julie A

    2008-02-11

    NAC1 is a novel member of the POZ/BTB (Pox virus and Zinc finger/Bric-a-bracTramtrack Broad complex) but varies from other proteins of this class in that it lacks the characteristic DNA-binding motif, suggesting a novel role. We have employed constitutive gene deletion to elucidate the role of NAC1 in vivo. Nac1 mutant mice are viable with no obvious developmental or physiological impairments. Previous studies suggest a role for NAC1 in cocaine-mediated behaviors. Therefore, we evaluated a variety of behaviors associated with psychomotor stimulant effects in Nac1 mutant mice. Acute locomotor activating effects of cocaine or amphetamine are absent in Nac1 mutant mice, however longer exposure to these psychomotor stimulants result in the development of behavioral sensitization. Acute rewarding properties of cocaine and amphetamine are also blunted in mutant mice, yet repeated exposure resulted in conditioned place preference similar to that observed in wild-type mice. Lastly, increases in extracellular dopamine in the nucleus accumbens, which accompany acute cocaine administration, are blunted in mutant mice, but following chronic cocaine extracellular dopamine levels are increased to the same extent as in wild-type mice. Together these data indicate involvement of NAC1 in the acute behavioral and neurochemical responses to psychomotor stimulants.

  13. [Amphetamine use by truck drivers on highways of Sao Paulo State: a risk for the occurrence of traffic accidents?].

    Science.gov (United States)

    Takitane, Juliana; de Oliveira, Lucio Garcia; Endo, Ligia Góes; de Oliveira, Keziah Cristina Barbosa Gruber; Muñoz, Daniel Romero; Yonamine, Mauricio; Leyton, Vilma

    2013-05-01

    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 traffic accidents and the related effects.

  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. Narcolepsy Treated with Racemic Amphetamine during Pregnancy and Breastfeeding.

    Science.gov (United States)

    Öhman, Inger; Wikner, Birgitta Norstedt; Beck, Olof; Sarman, Ihsan

    2015-08-01

    This case report describes a woman with narcolepsy treated with racemic amphetamine (rac-amphetamine) during pregnancy and breastfeeding with follow-up on the infant's development up to 10 months of age. The pregnancy outcome and the pharmacokinetics of rac-amphetamine were studied during breastfeeding. The pregnancy and the delivery were uneventful. Concentrations of rac-amphetamine were determined in the plasma of the mother and infant, and in the breast milk with a liquid chromatography-mass spectrometry method. Samples were obtained at 2, 5, and 9 weeks postpartum. The transfer of rac-amphetamine to the breast milk was extensive (mean milk/maternal plasma concentration ratio approximately 3). The breastfed infant had a low plasma concentration of rac-amphetamine (about 9% of the maternal plasma level) and the calculated relative infant dose was low (2%). No adverse effects were observed in the breastfed infant. The infant's somatic and psychomotor development up to 10 months of age was normal. Further studies of amphetamine prescribed for medical reasons during pregnancy and lactation are needed.

  16. Amphetamine in adolescence disrupts the development of medial prefrontal cortex dopamine connectivity in a DCC-dependent manner.

    Science.gov (United States)

    Reynolds, Lauren M; Makowski, Carolina S; Yogendran, Sandra V; Kiessling, Silke; Cermakian, Nicolas; Flores, Cecilia

    2015-03-13

    Initiation of drug use during adolescence is a strong predictor of both the incidence and severity of addiction throughout the lifetime. Intriguingly, adolescence is a period of dynamic refinement in the organization of neuronal connectivity, in particular medial prefrontal cortex (mPFC) dopamine circuitry. The guidance cue receptor, DCC (deleted in colorectal cancer), is highly expressed by dopamine neurons and orchestrates their innervation to the mPFC during adolescence. Furthermore, we have shown that amphetamine in adolescence regulates DCC expression in dopamine neurons. Drugs in adolescence may therefore induce their enduring behavioral effects via DCC-mediated disruption in mPFC dopamine development. In this study, we investigated the impact of repeated exposure to amphetamine during adolescence on both the development of mPFC dopamine connectivity and on salience attribution to drug context in adulthood. We compare these effects to those induced by adult exposure to an identical amphetamine regimen. Finally, we determine whether DCC signaling within dopamine neurons is necessary for these events. Exposure to amphetamine in adolescence, but not in adulthood, leads to an increase in the span of dopamine innervation to the mPFC, but a reduction of presynaptic sites present on these axons. Amphetamine treatment in adolescence, but not in adulthood, also produces an increase in salience attribution to a previously drug-paired context in adulthood. Remarkably, DCC signaling within dopamine neurons is required for both of these effects. Drugs of abuse in adolescence may therefore induce their detrimental behavioral consequences by disrupting mesocortical dopamine development through alterations in the DCC signaling cascade.

  17. Benzodiazepines and amphetamine on avoidance behaviour in mice.

    Science.gov (United States)

    Sansone, M

    1975-11-01

    Six benzodiazepine derivatives, given alone or in combination with amphetamine, were tested in mice subjected to five 100-trial avoidance sessions in the shuttle-box. All derivatives, execpt bromazepam, showed some facilitating effects on avoidance responding when given alone. Facilitation was particularly evident following the administration of chlordiazepoxide (2.5 mg/kg), medazepam (10 mg/kg) and nitrazepam (0.25, 0.5 and 1 mg/kg). Favourable effects were obtained by combining each benzodiazepine compound with amphetamine. The levels of avoidance respinses were usually higher under benzodiazepine-amphetamine combinations than under benzodiazepines alone.

  18. Microinjection of CART (cocaine- and amphetamine-regulated transcript) peptide into the nucleus accumbens inhibits the cocaine-induced upregulation of dopamine receptors and locomotor sensitization.

    Science.gov (United States)

    Peng, Qinghua; Sun, Xi; Liu, Ziyong; Yang, Jianghua; Oh, Ki-Wan; Hu, Zhenzhen

    2014-09-01

    Repeated exposure to addictive drugs enhances dopamine receptor (DR) signaling and the ultimate phosphorylation of the cyclic adenosine 5'-monophosphate (cAMP)-response element-binding protein (CREB)-regulated cocaine- and amphetamine-regulated transcript (CART) expression in the nucleus accumbens (NAcc). These effects are known to contribute to the expression of behavioral sensitization. CART peptides are neuropeptides that modulate drug reward and reinforcement. The present experiments investigated the effects of CART 55-102 microinjection into the NAcc on (1) the phosphorylation of CREB, (2) cAMP/protein kinase A (PKA) signaling and (3) extracellular signal-regulated kinase (ERK) phosphorylated kinase signaling. Here, we show that repeated microinjections into the NAcc of CART 55-102 peptides (1.0 or 2.5μg, 0.5μl/side) attenuates cocaine-induced enhancements of D1R, D2R and D3R phosphorylation in this sites. Furthermore, the microinjection of CART 55-102 followed by repeated injections of cocaine (15mg/kg) dose-dependently blocked the enhancement of cAMP levels, PKA activity and pERK and pCREB levels on the fifth day of cocaine administration. The cocaine-induced locomotor activity and behavioral sensitization in rats were also inhibited by the 5-day-microinjection of CART peptides. These results suggest that the phosphorylation of CREB by cocaine in the NAcc was blocked by the CART 55-102 peptide via the inhibition of D1R and D2R stimulation, D3R phosphorylation, cAMP/PKA signaling and ERK phosphorylated kinase signaling. These effects may have played a compensatory inhibitory role in the behavioral sensitization of rats that received microinjections of CART 55-102.

  19. GBR12909 attenuates amphetamine-induced striatal dopamine release as measured by [(11)C]raclopride continuous infusion PET scans.

    Science.gov (United States)

    Villemagne, V L; Wong, D F; Yokoi, F; Stephane, M; Rice, K C; Matecka, D; Clough, D J; Dannals, R F; Rothman, R B

    1999-09-15

    Major neurochemical effects of methamphetamine include release of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) via a carrier-mediated exchange mechanism. Preclinical research supports the hypothesis that elevations of mesolimbic DA mediate the addictive and reinforcing effects of methamphetamine and amphetamine. This hypothesis has not been adequately tested in humans. Previous in vivo rodent microdialysis demonstrated that the high affinity DA uptake inhibitor, GBR12909, attenuates cocaine- and amphetamine-induced increases in mesolimbic DA. The present study determined the ability of GBR12909 to attenuate amphetamine-induced increases in striatal DA as measured by [(11)C]raclopride continuous infusion positron emission tomography (PET) scans in two Papio anubis baboons. [(11)C]Raclopride was given in a continuous infusion paradigm resulting in a flat volume of distribution vs. time for up to 45 min postinjection. At that time, a 1.5 mg/kg amphetamine i.v. bolus was administered which caused a significant (30.3%) reduction in the volume of distribution (V(3)"). The percent reduction in the volume of distribution and, hence, a measure of the intrasynaptic DA release ranged between 22-41%. GBR12909 (1 mg/kg, slow i.v. infusion) was administered 90 min before the administration of the radiotracer. The comparison of the volume of distribution before and after administration of GBR12909 showed that GBR12909 inhibited amphetamine-induced DA release by 74%. These experiments suggest that GBR12909 is an important prototypical medication to test the hypothesis that stimulant-induced euphoria is mediated by DA and, if the DA hypothesis is correct, a potential treatment agent for cocaine and methamphetamine abuse. Furthermore, this quantitative approach demonstrates a way of testing various treatment medications, including other forms of GBR12909 such as a decanoate derivative.

  20. The Expression of Fos, Jun and AP-1 DNA Binding Activity in Rat Supraoptic Nucleus Neurons Following Acute Versus Repeated Osmotic Stimulation

    Science.gov (United States)

    1995-06-22

    stimulation. This pattern has been observed previously in the hippocampus after treatment with the seizure-inducing drug , metrazole (Sonnenberg et al... fosB , and fra-1 and -2. fra refers to ~OS­ ~elated ~ntigen. Western blot experiments and employment of less stringent nucleic acid hybridization...fos, fra-l and fosB , only form heterodimeric complexes with Jun-related proteins (Nakabeppu et al., 1988; Rauscher et al., 1988b) The AP-l site of many

  1. Progressive Seizure Aggravation in the Repeated 6-Hz Corneal Stimulation Model Is Accompanied by Marked Increase in Hippocampal p-ERK1/2 Immunoreactivity in Neurons

    Science.gov (United States)

    Giordano, Carmela; Costa, Anna M.; Lucchi, Chiara; Leo, Giuseppina; Brunel, Luc; Fehrentz, Jean-Alain; Martinez, Jean; Torsello, Antonio; Biagini, Giuseppe

    2016-01-01

    The 6-Hz corneal stimulation test is used to screen novel antiepileptic molecules to overcome the problem of drug refractoriness. Although recognized as a standard test, it has been evaluated only recently in the attempt to characterize the putative neuronal networks involved in seizures caused by corneal stimulation. In particular, by recording from the CA1 region we previously established that the hippocampus participates to propagation of seizure activity. However, these findings were not corroborated by using markers of neuronal activation such as FosB/ΔFosB antigens. In view of this discrepancy, we performed new experiments to characterize the changes in levels of phosphorylated extracellular signal-regulated kinases1/2 (p-ERK1/2), which are also used as markers of neuronal activation. To this aim, mice underwent corneal stimulation up to three different times, in three sessions separated by an interval of 3 days. To characterize a group in which seizures could be prevented by pharmacological treatment, we also considered pretreatment with the ghrelin receptor antagonist EP-80317 (330 μg/kg). Control mice were sham-treated. Video electrocorticographic (ECoG) recordings were obtained from mice belonging to each group of treatment. Animals were finally used to characterize the immunoreactivity for FosB/ΔFosB and p-ERK1/2 in the hippocampus. As previously shown, FosB/ΔFosB levels were highly increased throughout the hippocampus by the first induced seizure but, in spite of the progressively increased seizure severity, they were restored to control levels after the third stimulation. At variance, corneal stimulation caused a progressive increase in p-ERK1/2 immunoreactivity all over the hippocampus, especially in CA1, peaking in the third session. Predictably, EP-80317 administration reduced both duration and severity of seizures, prevented the increase in FosB/ΔFosB levels in the first session, and partially counteracted the increase in p-ERK1/2 levels in

  2. New Repeat Polymorphism in the AKT1 Gene Predicts Striatal Dopamine D2/D3 Receptor Availability and Stimulant-Induced Dopamine Release in the Healthy Human Brain.

    Science.gov (United States)

    Shumay, Elena; Wiers, Corinde E; Shokri-Kojori, Ehsan; Kim, Sung Won; Hodgkinson, Colin A; Sun, Hui; Tomasi, Dardo; Wong, Christopher T; Weinberger, Daniel R; Wang, Gene-Jack; Fowler, Joanna S; Volkow, Nora D

    2017-05-10

    The role of the protein kinase Akt1 in dopamine neurotransmission is well recognized and has been implicated in schizophrenia and psychosis. However, the extent to which variants in the AKT1 gene influence dopamine neurotransmission is not well understood. Here we investigated the effect of a newly characterized variant number tandem repeat (VNTR) polymorphism in AKT1 [major alleles: L- (eight repeats) and H- (nine repeats)] on striatal dopamine D2/D3 receptor (DRD2) availability and on dopamine release in healthy volunteers. We used PET and [(11)C]raclopride to assess baseline DRD2 availability in 91 participants. In 54 of these participants, we also measured intravenous methylphenidate-induced dopamine release to measure dopamine release. Dopamine release was quantified as the difference in specific binding of [(11)C]raclopride (nondisplaceable binding potential) between baseline values and values following methylphenidate injection. There was an effect of AKT1 genotype on DRD2 availability at baseline for the caudate (F(2,90) = 8.2, p = 0.001) and putamen (F(2,90) = 6.6, p = 0.002), but not the ventral striatum (p = 0.3). For the caudate and putamen, LL showed higher DRD2 availability than HH; HL were in between. There was also a significant effect of AKT1 genotype on dopamine increases in the ventral striatum (F(2,53) = 5.3, p = 0.009), with increases being stronger in HH > HL > LL. However, no dopamine increases were observed in the caudate (p = 0.1) or putamen (p = 0.8) following methylphenidate injection. Our results provide evidence that the AKT1 gene modulates both striatal DRD2 availability and dopamine release in the human brain, which could account for its association with schizophrenia and psychosis. The clinical relevance of the newly characterized AKT1 VNTR merits investigation.SIGNIFICANCE STATEMENT The AKT1 gene has been implicated in schizophrenia and psychosis. This association is likely to reflect modulation of dopamine signaling by Akt1 kinase

  3. Amphetamine-related ischemic colitis causing gastrointestinal bleeding

    OpenAIRE

    Panikkath, Ragesh; Panikkath, Deepa

    2016-01-01

    A 43-year-old woman presented with acute lower intestinal bleeding requiring blood transfusion. Multiple initial investigations did not reveal the cause of the bleeding. Colonoscopy performed 2 days later showed features suggestive of ischemic colitis. On detailed history, the patient admitted to using amphetamines, and her urine drug screen was positive for them. She was managed conservatively and advised not to use amphetamines again. She did not have any recurrence on 2-year follow-up.

  4. Amphetamine-related ischemic colitis causing gastrointestinal bleeding

    Science.gov (United States)

    Panikkath, Deepa

    2016-01-01

    A 43-year-old woman presented with acute lower intestinal bleeding requiring blood transfusion. Multiple initial investigations did not reveal the cause of the bleeding. Colonoscopy performed 2 days later showed features suggestive of ischemic colitis. On detailed history, the patient admitted to using amphetamines, and her urine drug screen was positive for them. She was managed conservatively and advised not to use amphetamines again. She did not have any recurrence on 2-year follow-up. PMID:27365888

  5. Occurrence and Potential Biological Effects of Amphetamine on Stream Communities.

    Science.gov (United States)

    Lee, Sylvia S; Paspalof, Alexis M; Snow, Daniel D; Richmond, Erinn K; Rosi-Marshall, Emma J; Kelly, John J

    2016-09-06

    The presence of pharmaceuticals, including illicit drugs in aquatic systems, is a topic of environmental significance because of their global occurrence and potential effects on aquatic ecosystems and human health, but few studies have examined the ecological effects of illicit drugs. We conducted a survey of several drug residues, including the potentially illicit drug amphetamine, at 6 stream sites along an urban to rural gradient in Baltimore, Maryland, U.S.A. We detected numerous drugs, including amphetamine (3 to 630 ng L(-1)), in all stream sites. We examined the fate and ecological effects of amphetamine on biofilm, seston, and aquatic insect communities in artificial streams exposed to an environmentally relevant concentration (1 μg L(-1)) of amphetamine. The amphetamine parent compound decreased in the artificial streams from less than 1 μg L(-1) on day 1 to 0.11 μg L(-1) on day 22. In artificial streams treated with amphetamine, there was up to 45% lower biofilm chlorophyll a per ash-free dry mass, 85% lower biofilm gross primary production, 24% greater seston ash-free dry mass, and 30% lower seston community respiration compared to control streams. Exposing streams to amphetamine also changed the composition of bacterial and diatom communities in biofilms at day 21 and increased cumulative dipteran emergence by 65% and 89% during the first and third weeks of the experiment, respectively. This study demonstrates that amphetamine and other biologically active drugs are present in urban streams and have the potential to affect both structure and function of stream communities.

  6. Amphetamine self-administration attenuates dopamine D2 autoreceptor function.

    Science.gov (United States)

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

    2014-07-01

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

  7. Amphetamine Self-Administration Attenuates Dopamine D2 Autoreceptor Function

    Science.gov (United States)

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

    2014-01-01

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

  8. Diet-induced obesity and diet-resistant rats: differences in the rewarding and anorectic effects of D-amphetamine.

    Science.gov (United States)

    Valenza, Marta; Steardo, Luca; Cottone, Pietro; Sabino, Valentina

    2015-09-01

    Obesity is a leading public health problem worldwide. Multiple lines of evidence associate deficits in the brain reward circuit with obesity. Whether alterations in brain reward sensitivity precede or are a consequence of obesity is unknown. This study aimed to investigate both innate and obesity-induced differences in the sensitivity to the effects of an indirect dopaminergic agonist. Rats genetically prone to diet-induced obesity (DIO) and their counterpart diet-resistant (DR) were fed a chow diet, and their response to D-amphetamine on intracranial self-stimulation and food intake were assessed. The same variables were then evaluated after exposing the rats to a high-fat diet, after DIO rats selectively developed obesity. Finally, gene expression levels of dopamine receptors 1 and 2 as well as tyrosine hydroxylase were measured in reward-related brain regions. In a pre-obesity state, DIO rats showed innate decreased sensitivity to the reward-enhancing and anorectic effects of D-amphetamine, as compared to DR rats. In a diet-induced obese state, the insensitivity to the potentiating effects of D-amphetamine on intracranial self-stimulation (ICSS) threshold persisted and became more marked in DIO rats, while the anorectic effects were comparable between genotypes. Finally, innate and obesity-induced differences in the gene expression of dopamine receptors were observed. Our results demonstrate that brain reward deficits antedate the development of obesity and worsen after obesity is fully developed, suggesting that these alterations represent vulnerability factors for its development. Moreover, our data suggests that the reward-enhancing and anorectic effects of D-amphetamine are dissociable in the context of obesity.

  9. The neurotoxicity of hallucinogenic amphetamines in primary cultures of hippocampal neurons.

    Science.gov (United States)

    Capela, João Paulo; da Costa Araújo, Silvana; Costa, Vera Marisa; Ruscher, Karsten; Fernandes, Eduarda; Bastos, Maria de Lourdes; Dirnagl, Ulrich; Meisel, Andreas; Carvalho, Félix

    2013-01-01

    3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) are hallucinogenic amphetamines with addictive properties. The hippocampus is involved in learning and memory and seems particularly vulnerable to amphetamine's neurotoxicity. We evaluated the neurotoxicity of DOI and MDMA in primary neuronal cultures of hippocampus obtained from Wistar rat embryos (E-17 to E-19). Mature neurons after 10 days in culture were exposed for 24 or 48 h either to MDMA (100-800 μM) or DOI (10-100 μM). Both the lactate dehydrogenase (LDH) release and the tetrazolium-based (MTT) assays revealed a concentration- and time-dependent neuronal death and mitochondrial dysfunction after exposure to both drugs. Both drugs promoted a significant increase in caspase-8 and caspase-3 activities. At concentrations that produced similar levels of neuronal death, DOI promoted a higher increase in the activity of both caspases than MDMA. In the mitochondrial fraction of neurons exposed 24h to DOI or MDMA, we found a significant increase in the 67 kDa band of apoptosis inducing factor (AIF) by Western blot. Moreover, 24h exposure to DOI promoted an increase in cytochrome c in the cytoplasmatic fraction of neurons. Pre-treatment with an antibody raised against the 5-HT(2A)-receptor (an irreversible antagonist) greatly attenuated neuronal death promoted by 48 h exposure to DOI or MDMA. In conclusion, hallucinogenic amphetamines promoted programmed neuronal death involving both the mitochondria machinery and the extrinsic cell death key regulators. Death was dependent, at least in part, on the stimulation of the 5-HT(2A)-receptors.

  10. Abuse of amphetamines and structural abnormalities in the brain.

    Science.gov (United States)

    Berman, Steven; O'Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D

    2008-10-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques including manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

  11. Association of Leukocytosis with Amphetamine and Cocaine Use

    Directory of Open Access Journals (Sweden)

    John R. Richards

    2014-01-01

    Full Text Available Objective. Determining the etiology of unexplained leukocytosis in asymptomatic patients may incur unnecessary testing, cost, and prolonged emergency department stay. The objective was to delineate if use of amphetamines and/or cocaine is a factor. Methods. For two years we reviewed all psychiatric patients presenting for medical clearance with exclusions for infection, epilepsy, trauma, or other nonpsychiatric medical conditions. Results. With a total of 1,206 patients, 877 (72.7% amphetamines/cocaine-negative drug screen controls had mean WBC 8.4±2.6×103/µL. The 240 (19.9% amphetamines-positive, cocaine-negative, patients had WBC 9.4±3.3×103/µL (P<0.0001. The 72 (6.0% amphetamines-negative, cocaine-positive, patients had WBC 7.1±1.8×103/µL (P<0.0001. The remaining 17 (1.4% amphetamines/cocaine-positive patients had WBC 10.0±4.2×103/µL (P=0.01. Amphetamines-positive patients had a supranormal WBC ratio significantly higher than controls (23.8% versus 14.8%, P=0.001, whereas only one cocaine-positive patient had a supranormal WBC count, with significantly lower ratio (1.4%, P=0.0003. Conclusion. Use of amphetamines, not cocaine, may be associated with idiopathic leukocytosis. This may be explained by unique pharmacologic, neuroendocrine, and immunomodulatory differences.

  12. 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.

  13. Recombinant myxoma virus lacking all poxvirus ankyrin-repeat proteins stimulates multiple cellular anti-viral pathways and exhibits a severe decrease in virulence.

    Science.gov (United States)

    Lamb, Stephanie A; Rahman, Masmudur M; McFadden, Grant

    2014-09-01

    Although the production of single gene knockout viruses is a useful strategy to study viral gene functions, the redundancy of many host interactive genes within a complex viral genome can obscure their collective functions. In this study, a rabbit-specific poxvirus, myxoma virus (MYXV), was genetically altered to disrupt multiple members of the poxviral ankyrin-repeat (ANK-R) protein superfamily, M-T5, M148, M149 and M150. A particularly robust activation of the NF-κB pathway was observed in A549 cells following infection with the complete ANK-R knockout (vMyx-ANKsKO). Also, an increased release of IL-6 was only observed upon infection with vMyx-ANKsKO. In virus-infected rabbit studies, vMyx-ANKsKO was the most extensively attenuated and produced the smallest primary lesion of all ANK-R mutant constructs. This study provides the first insights into the shared functions of the poxviral ANK-R protein superfamily in vitro and in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Terahertz spectroscopic investigation of methylenedioxy amphetamine

    Science.gov (United States)

    Wang, Guangqin; Shen, Jingling

    2008-03-01

    Experimental measurement and theoretical analysis of THz spectrum for methylenedioxy amphetamine are introduced. The refractive index and absorption coefficient of the sample were observed by terahertz time-domain spectroscopy (THz-TDS) technique in the range of 0.2~2.6 THz. It exhibits obvious absorption feature at 1.40 THz and weak THz absorption at around 1.68 and 2.21 THz. The spectral absorption characteristic in THz band was useful for the inspection and identification of drugs using THz-TDS. The theoretical calculation was performed using Density functional theory (DFT) with the GAUSSIAN 03 software package. Fully geometry optimization and frequency analysis of the optimized structure were performed at the B3LYP/6-21G levels. The simulated absorption spectrum was in agreement with the experimental data, and can hence be used for the assignment of observed THz spectrum. The theoretical simulation result showed that absorption peaks mainly result from intra-molecule and inter-molecule vibrations, different absorption peaks are corresponding to different vibrational modes and intensity. So the combination of the THz-TDS and DFT is an effective way to investigate characteristic spectra of illicit drugs.

  15. The effect of repeated administrations of granulocyte colony stimulating factor for blood stem cells mobilization in patients with progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy.

    Science.gov (United States)

    Pezzoli, Gianni; Tesei, Silvana; Canesi, Margherita; Sacilotto, Giorgio; Vittorio, Montefusco; Mizuno, Yoshi; Mochizuki, Hideki; Antonini, Angelo

    2010-01-01

    Granulocyte colony stimulating factor (GCSF) may boost physiological stem cell repair system in patients with cerebral lesions. Atypical parkinsonisms (PSP, CBD, MSA) are characterized by rapidly progressive course without significant benefit from current therapies. We treated 11 patients with atypical parkinsonism (MSA n=4, PSP n=5, CBD n=2) with GCSF (5mcg/kg s.c. daily for 6 days/month) for 3 months. We assessed CBC, CD34+ cells, routine biochemical and coagulation tests, UPDRS motor scores and safety. We did not observe significant adverse events during and following GCSF treatment. One patient withdrew informed consent. Three patients complained about bone pain that improved following steroid treatment. Four patients perceived a subjective benefit after treatment was completed. UPDRS motor score improved in three patients, remained stable in two and worsened in five. GCSF can be safely administered to patients with atypical parkinsonism and potentially meaningful clinical changes may be observed in some patients. These results are encouraging and warrant further studies. 2009 Elsevier B.V. All rights reserved.

  16. Ultra-performance liquid chromatography-tandem mass spectrometry method for the analysis of amphetamines in plasma.

    Science.gov (United States)

    Fernández, María del Mar Ramírez; Samyn, Nele

    2011-10-01

    A fast and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of amphetamines (amphetamine, methamphetamine, methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, ephedrine, and p-methoxyamphetamine) in plasma has been developed and validated. Sample preparation was performed by liquid-liquid extraction using ethyl acetate. For optimized chromatographic performance with repeatable retention times, narrow and symmetrical peaks, and focusing all analytes at the column inlet, a gradient start, with acid mobile phase consisting of 0.1% formic acid and methanol was chosen. Positive electrospray ionization MS-MS detection was performed with two multiple reaction monitoring transitions for each analyte. Deuteriumlabeled internal standards were used for five of the analytes. The limit of detection was in the range 0.25-1.25 ng/mL, and the limit of quantification was fixed at the lowest calibrator of 2.5 ng/mL for all of the compounds. The RSD values of the intra- and interassay precision and accuracy were lower than 11% at four concentration levels, including two external quality controls. No or only minor matrix effects were observed, and the extraction method presented recoveries higher than 93% for all the compounds. Total run time, including equilibration, was 12 min. The method is routinely used at the National Institute of Criminalistics and Criminology for quantitative determination of the main amphetamines in plasma from forensic and driving under the influence cases.

  17. Another look at amphetamine-induced stereotyped locomotor activity in rats using a new statistic to measure locomotor stereotypy.

    Science.gov (United States)

    Mueller, K; Hollingsworth, E M; Cross, D R

    1989-01-01

    Rat open field behavior is often used as a tool to study the behavioral effects of drugs. In this report, drug-induced patterns of locomotion in an open field were studied with the aid of a simple new statistic. Briefly, the animal's path through the open field is converted into a series of trips. Gamma (gamma) estimates the probability that the animal will repeat the trip that it has just exhibited; thus gamma quantifies "locomotor stereotypy". Trip lengths can also be compared across drug groups. Thus caffeine has no effect on gamma even though it produces a dose-related increase in locomotions. Caffeine does not produce amphetamine-like stereotypy. On the other hand, amphetamine produces a dose-related increase in gamma. Although gamma was designed to detect any pattern of locomotor behavior, rats treated with high doses of amphetamine almost always exhibited the same pattern of locomotor behavior - repetitive trips around the perimeter of the open field. Although further characterization of the statistic is necessary, these findings suggest that gamma has potential for quantifying "locomotor stereotypy" and for providing a more subtle description of locomotor behavior in general.

  18. Medico-legal aspect of amphetamine-related deaths

    Directory of Open Access Journals (Sweden)

    Karol Kula

    2014-12-01

    Full Text Available The subject of the work included 41 cases of death in which amphetamine was involved as the direct or indirect cause. Identification and determination of xenobiotics in blood samples collected from post-mortem cases were performed by high-performance liquid chromatography coupled with tandem mass spectrometry with electrospray ionisation (HPLC-ESI-MS-MS. Only for two cases was the cause of death amphetamine poisoning. In most of the investigated cases the death was caused by poisoning due to complex amphetamine and other psychoactive substances (e.g. opiates, benzodiazepines, cocaine. In other cases, multi-organ damage (fall from a height, traffic accident, a puncture wound and wound incised, drowning, or asphyxiation by hanging were reported. It can be explained as risky, murderous, or suicidal actions of people who were under the influence of amphetamines. The presented paper focuses on the interpretation of amphetamine concentration in blood samples from the perspective of direct or indirect cause of death.

  19. The secondary structure of the R region of a murine leukemia virus is important for stimulation of long terminal repeat-driven gene expression.

    Science.gov (United States)

    Cupelli, L; Okenquist, S A; Trubetskoy, A; Lenz, J

    1998-10-01

    In addition to their role in reverse transcription, the R-region sequences of some retroviruses affect viral transcription. The first 28 nucleotides of the R region within the long terminal repeat (LTR) of the murine type C retrovirus SL3 were predicted to form a stem-loop structure. We tested whether this structure affected the transcriptional activity of the viral LTR. Mutations that altered either side of the stem and thus disrupted base pairing were generated. These decreased the level of expression of a reporter gene under the control of viral LTR sequences about 5-fold in transient expression assays and 10-fold in cells stably transformed with the LTR-reporter plasmids. We also generated a compensatory mutant in which both the ascending and descending sides of the stem were mutated such that the nucleotide sequence was different but the predicted secondary structure was maintained. Most of the activity of the wild-type SL3 element was restored in this mutant. Thus, the stem-loop structure was important for the maximum activity of the SL3 LTR. Primer extension analysis indicated that the stem-loop structure affected the levels of cytoplasmic RNA. Nuclear run-on assays indicated that deletion of the R region had a small effect on transcriptional initiation and no effect on RNA polymerase processivity. Thus, the main effect of the R-region element was on one or more steps that occurred after the template was transcribed by RNA polymerase. This finding implied that the main function of the R-region element involved RNA processing. R-region sequences of human immunodeficiency virus type 1 or mouse mammary tumor virus could not replace the SL3 element. R-region sequences from an avian reticuloendotheliosis virus partially substituted for the SL3 sequences. R-region sequences from Moloney murine leukemia virus or feline leukemia virus did function in place of the SL3 element. Thus, the R region element appears to be a general feature of the mammalian type C genus of

  20. 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.

  1. New Psychoactive Substances: Chemistry, Pharmacology, Metabolism, and Detectability of Amphetamine Derivatives With Modified Ring Systems.

    Science.gov (United States)

    Welter-Luedeke, Jessica; Maurer, Hans H

    2016-02-01

    In recent years, new amphetamine derivatives with modified ring systems were sold and consumed as new drugs of abuse. They belong together with other new drugs of abuse classes to the so-called new psychoactive substances (NPS). The chemistry, pharmacology, toxicology, metabolism, and toxicokinetics are shortly discussed of camfetamine, 3 methylphenyl-amphetamines (2-MA, 3-MA, and 4-MA), 2-methiopropamine (2-MPA), and 5-(2-aminopropyl)benzofuran (5-APB), 6-(2-aminopropyl)benzofuran (6-APB, so-called "benzofury") and their N-methyl derivatives 5-MAPB and 6-MAPB. Only a rough assessment of the pharmacology and toxicology NPS can be performed in most cases using published data of analogs, trip reports, and described clinical cases. Accordingly, they all act more or less as central nervous stimulants mainly by increasing the concentration of the neurotransmitters noradrenaline, dopamine, and serotonin (5-HT) by inducing their release and reuptake inhibition. Thus, the acute toxicity is associated with the sympathomimetic effects, such as mydriasis, hyperthermia, hypertension, tachycardia, insomnia, and anxiety. With the exception of 5- and 6-APB, these NPS were extensively metabolized by N-demethylation and/or aromatic hydroxylation catalyzed by various cytochrome P450 isoenzymes followed by partial glucuronidation and/or sulfation. For urinalysis, the unchanged drugs and/or the nor-metabolites are the main targets.

  2. Brain-specific overexpression of trace amine-associated receptor 1 alters monoaminergic neurotransmission and decreases sensitivity to amphetamine.

    Science.gov (United States)

    Revel, Florent G; Meyer, Claas A; Bradaia, Amyaouch; Jeanneau, Karine; Calcagno, Eleonora; André, Cédric B; Haenggi, Markus; Miss, Marie-Thérèse; Galley, Guido; Norcross, Roger D; Invernizzi, Roberto W; Wettstein, Joseph G; Moreau, Jean-Luc; Hoener, Marius C

    2012-11-01

    Trace amines (TAs) such as β-phenylethylamine, p-tyramine, or tryptamine are biogenic amines found in the brain at low concentrations that have been implicated in various neuropsychiatric disorders like schizophrenia, depression, or attention deficit hyperactivity disorder. TAs are ligands for the recently identified trace amine-associated receptor 1 (TAAR1), an important modulator of monoamine neurotransmission. Here, we sought to investigate the consequences of TAAR1 hypersignaling by generating a transgenic mouse line overexpressing Taar1 specifically in neurons. Taar1 transgenic mice did not show overt behavioral abnormalities under baseline conditions, despite augmented extracellular levels of dopamine and noradrenaline in the accumbens nucleus (Acb) and of serotonin in the medial prefrontal cortex. In vitro, this was correlated with an elevated spontaneous firing rate of monoaminergic neurons in the ventral tegmental area, dorsal raphe nucleus, and locus coeruleus as the result of ectopic TAAR1 expression. Furthermore, Taar1 transgenic mice were hyposensitive to the psychostimulant effects of amphetamine, as it produced only a weak locomotor activation and failed to alter catecholamine release in the Acb. Attenuating TAAR1 activity with the selective partial agonist RO5073012 restored the stimulating effects of amphetamine on locomotion. Overall, these data show that Taar1 brain overexpression causes hyposensitivity to amphetamine and alterations of monoaminergic neurotransmission. These observations confirm the modulatory role of TAAR1 on monoamine activity and suggest that in vivo the receptor is either constitutively active and/or tonically activated by ambient levels of endogenous agonist(s).

  3. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine... and the methamphetamine they contain is being used as a substitute for amphetamine...

  4. Amphetamines, new psychoactive drugs and the monoamine transporter cycle.

    Science.gov (United States)

    Sitte, Harald H; Freissmuth, Michael

    2015-01-01

    In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit their actions: most amphetamines are substrates, which pervert the relay to elicit efflux of monoamines into the synaptic cleft. However, some amphetamines act as transporter inhibitors. Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse. Currently, a surge of new psychoactive substances occurs on a global scale. Chemists bypass drug bans by ingenuous structural variations, resulting in a rich pharmacology. A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects.

  5. Amphetamines, new psychoactive drugs and the monoamine transporter cycle

    Science.gov (United States)

    Sitte, Harald H.; Freissmuth, Michael

    2015-01-01

    In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit their actions: most amphetamines are substrates, which pervert the relay to elicit efflux of monoamines into the synaptic cleft. However, some amphetamines act as transporter inhibitors. Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse. Currently, a surge of new psychoactive substances occurs on a global scale. Chemists bypass drug bans by ingenuous structural variations, resulting in a rich pharmacology. A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects. PMID:25542076

  6. Stress-Induced Locomotor Sensitization to Amphetamine in Adult, but not in Adolescent Rats, Is Associated with Increased Expression of ΔFosB in the Nucleus Accumbens

    Science.gov (United States)

    Carneiro de Oliveira, Paulo E.; Leão, Rodrigo M.; Bianchi, Paula C.; Marin, Marcelo T.; Planeta, Cleopatra da Silva; Cruz, Fábio C.

    2016-01-01

    While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively) were restrained for 2 h once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both the adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats. PMID:27672362

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

    Directory of Open Access Journals (Sweden)

    Paulo Eduardo Carneiro de Oliveira

    2016-09-01

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

  8. Bupropion interference with immunoassays for amphetamines and LSD.

    Science.gov (United States)

    Vidal, Christian; Skripuletz, Thomas

    2007-06-01

    A 50-year-old male patient suddenly had lost consciousness, although he had previously been healthy. On arrival at hospital seizures arose. The authors investigated a urine sample of the patient, and performed toxicological drug screening with immunochemical Cloned Enzyme Donor Immunoassay (CEDIA) assays. Positive findings for amphetamines and LSD could not be confirmed. Using gas chromatography/mass spectrometry (GC/MS), and liquid chromatography/mass spectrometry (LC/MS), the authors identified bupropion, a drug used to aid in smoking cessation, as the interfering compound, which may cause false-positive results for amphetamines and LSD using the CEDIA assays.

  9. Oral Fluid with Three Modes of Collection and Plasma Methamphetamine and Amphetamine Enantiomer Concentrations After Controlled Intranasal l-Methamphetamine Administration

    OpenAIRE

    Newmeyer, Matthew N.; Concheiro, Marta; da Costa, Jose Luiz; Flegel, Ronald; Gorelick, David A.; Huestis, Marilyn A.

    2015-01-01

    Methamphetamine is included in drug testing programs due to its high abuse potential. d-Methamphetamine is a scheduled potent central nervous system stimulant, while l-methamphetamine is the unscheduled active ingredient in the over-the-counter nasal decongestant Vicks® VapoInhaler™. No data are available in oral fluid (OF) and few in plasma after controlled Vicks VapoInhaler administration. We quantified methamphetamine and amphetamine enantiomers in OF collected with two different devices a...

  10. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    controlled to great precision, but in a Cubesat , there may be no attitude determination at all. Such a Cubesat might treat sun angle and tumbling rates as...could be sensitive to small differences in motor controller timing. In these cases, the analyst might choose to model the entire deployment path, with...knowledge of the material damage model or motor controller timing precision. On the other hand, if many repeated and environmentally representative

  11. Formation and reverberation of sequential neural activity patterns evoked by sensory stimulation are enhanced during cortical desynchronization.

    Science.gov (United States)

    Bermudez Contreras, Edgar J; Schjetnan, Andrea Gomez Palacio; Muhammad, Arif; Bartho, Peter; McNaughton, Bruce L; Kolb, Bryan; Gruber, Aaron J; Luczak, Artur

    2013-08-07

    Memory formation is hypothesized to involve the generation of event-specific neural activity patterns during learning and the subsequent spontaneous reactivation of these patterns. Here, we present evidence that these processes can also be observed in urethane-anesthetized rats and are enhanced by desynchronized brain state evoked by tail pinch, subcortical carbachol infusion, or systemic amphetamine administration. During desynchronization, we found that repeated tactile or auditory stimulation evoked unique sequential patterns of neural firing in somatosensory and auditory cortex and that these patterns then reoccurred during subsequent spontaneous activity, similar to what we have observed in awake animals. Furthermore, the formation of these patterns was blocked by an NMDA receptor antagonist, suggesting that the phenomenon depends on synaptic plasticity. These results suggest that anesthetized animals with a desynchronized brain state could serve as a convenient model for studying stimulus-induced plasticity to improve our understanding of memory formation and replay in the brain.

  12. Amphetamines modulate prefrontal γ oscillations during attention processing.

    Science.gov (United States)

    Franzen, John D; Wilson, Tony W

    2012-08-22

    Amphetamine-based medications robustly suppress symptoms of attention-deficit/hyperactivity disorder (ADHD), but their exact mechanisms remain poorly understood. Recent hemodynamic imaging studies have suggested that amphetamines may modulate the prefrontal and anterior cingulate brain regions, although few studies have been published and the results have not been entirely consistent. Meanwhile, several electrophysiological studies have shown that abnormal fast oscillations (in the γ range) may be closely linked to inattention and other cardinal symptoms of ADHD. In this study, we utilized magnetoencephalography to examine how amphetamines modulate high-frequency brain activity in adults with ADHD. Participants performed an auditory attention task, which required sustained attention in one block and passive listening in a separate block. Participants completed the task twice in the on-medication and off-medication states. All data were analyzed using beamforming techniques to resolve cortical regions showing event-related synchronizations and desynchronizations. Our primary findings indicated that oral administration of amphetamine decreased γ-band event-related desynchronization activity significantly in the medial prefrontal area and decreased event-related synchronization in bilateral superior parietal areas, left inferior parietal, and the left inferior frontal gyrus. These results suggest that psychostimulants strongly modulate γ activity in frontal and parietal cortical areas, which are known to be central to the brain's core attentional networks.

  13. Amphetamine Containing Dietary Supplements and Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Julio Perez-Downes

    2016-01-01

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

  14. The Effect of Variant Dosages of Amphetamine Upon Endurance.

    Science.gov (United States)

    Williams, Melvin H.; Thompson, John

    The purpose of this study was to provide basic information concerning the acute effects of a small, moderate, and large dose of d-amphetamine sulfate upon muscular endurance; a secondary purpose involved the effect upon resting (R), and submaximal, and maximal (MAX) heart rate (HR). Twelve male university students underwent four separate trials of…

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

    Directory of Open Access Journals (Sweden)

    Elham Bazmi

    2017-03-01

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

  16. PRESYNAPTIC DOPAMINE MODULATION BY STIMULANT SELF ADMINISTRATION

    Science.gov (United States)

    España, Rodrigo A.; Jones, Sara R.

    2013-01-01

    The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine. PMID:23277050

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

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Thanos, P.K.; Bermeo, C.; Rubinstein, M.; Suchland, K.L.; Wang, G.-J.; Grandy, D.K.; Volkow, N.D.

    2010-05-01

    Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs

  18. Influence of benzodiazepine tranquilizers on scopolamine-induced locomotor stimulation in mice.

    Science.gov (United States)

    Sansone, M

    1980-01-01

    Four benzodiazepine tranquilizers have been tested, alone or in combination with scopolamine, on the spontaneous locomotor activity of BALB/c mice. Scopolamine-induced locomotor stimulation was enhanced by chlordiazepoxide, diazepam, and medazepam, but not by bromazepam. These effects are similar to those exerted by the four benzodiazepines on amphetamine-induced locomotor stimulation and allow the same differentiation between the four derivatives.

  19. Augmented reinforcer value and accelerated habit formation after repeated amphetamine treatment.

    NARCIS (Netherlands)

    Nordquist, R.E.; Voorn, P.; de Mooij-van Malsen, J.G.; Joosten, R.N.J.M.A.; Pennartz, C.M.A.; Vanderschuren, L.J.M.J.

    2007-01-01

    Various processes might explain the progression from casual to compulsive drug use underlying the development of drug addiction. Two of these, accelerated stimulus-response (S-R) habit learning and augmented assignment of motivational value to reinforcers, could be mediated via neuroadaptations asso

  20. Meth/amphetamine use and associated HIV: Implications for global policy and public health.

    Science.gov (United States)

    Degenhardt, Louisa; Mathers, Bradley; Guarinieri, Mauro; Panda, Samiran; Phillips, Benjamin; Strathdee, Steffanie A; Tyndall, Mark; Wiessing, Lucas; Wodak, Alex; Howard, John

    2010-09-01

    Amphetamine type stimulants (ATS) have become the focus of increasing attention worldwide. There are understandable concerns over potential harms including the transmission of HIV. However, there have been no previous global reviews of the extent to which these drugs are injected or levels of HIV among users. A comprehensive search of the international peer-reviewed and grey literature was undertaken. Multiple electronic databases were searched and documents and datasets were provided by UN agencies and key experts from around the world in response to requests for information on the epidemiology of use. Amphetamine or methamphetamine (meth/amphetamine, M/A) use was documented in 110 countries, and injection in 60 of those. Use may be more prevalent in East and South East Asia, North America, South Africa, New Zealand, Australia and a number of European countries. In countries where the crystalline form is available, evidence suggests users are more likely to smoke or inject the drug; in such countries, higher levels of dependence may be occurring. Equivocal evidence exists as to whether people who inject M/A are at differing risk of HIV infection than other drug injectors; few countries document HIV prevalence/incidence among M/A injectors. High risk sexual behaviour among M/A users may contribute to increased risk of HIV infection, but available evidence is not sufficient to determine if the association is causal. A range of possible responses to M/A use and harm are discussed, ranging from supply and precursor control, to demand and harm reduction. Evidence suggests that complex issues surround M/A, requiring novel and sophisticated approaches, which have not yet been met with sufficient investment of time or resources to address them. Significant levels of M/A in many countries require a response to reduce harms that in many cases remain poorly understood. More active models of engagement with M/A users and provision of services that meet their specific needs

  1. Amphetamine Positive Urine Toxicology Screen Secondary to Atomoxetine

    OpenAIRE

    Fenderson, Joshua L.; Stratton, Amy N; Domingo, Jennifer S.; Matthews, Gerald O.; Tan, Christopher D.

    2013-01-01

    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 substan...

  2. Maternal separation altered behavior and neuronal spine density without influencing amphetamine sensitization.

    Science.gov (United States)

    Muhammad, Arif; Kolb, Bryan

    2011-09-30

    We studied the long-term influence of maternal separation (MS) on periadolescent behavior, adult amphetamine (AMPH) sensitization, and structural plasticity in the corticolimbic regions in rats. Male and female pups, separated daily for 3h from the dam during postnatal day 3-21, were tested for periadolescent exploratory, emotional, cognitive, and social behaviors. The development and persistence of drug-induced behavioral sensitization were tested by repeated AMPH administration and a challenge, respectively. The spine density was examined in the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and the orbital frontal cortex (OFC) from Golgi-Cox stained neurons. The results showed that MS enhanced anxiety-like behavior in males. MS abolished the sex difference in playful attacks observed in controls with resultant feminization of male play behavior. Furthermore, the probability of complete rotation defense to face an attack was decreased in females. AMPH administration resulted in the development of behavioral sensitization that persisted at least for two weeks. Sensitization was not influenced by MS. MS increased the spine density in the NAc, the mPFC, and the OFC. Repeated AMPH administration increased the spine density in the NAc and the mPFC, and decreased it in the OFC. MS blocked the drug-induced alteration in these regions. In sum, MS during development influenced periadolescent behavior in males, and structurally reorganized cortical and subcortical brain regions without affecting AMPH-induced behavioral sensitization.

  3. The Basal Ganglia as a Substrate for the Multiple Actions of Amphetamines

    OpenAIRE

    Natarajan, Reka; Yamamoto, Bryan K.

    2011-01-01

    Amphetamines are psychostimulant drugs with high abuse potential. Acute and chronic doses of amphetamines affect dopamine (DA) neurotransmission in the basal ganglia. The basal ganglia are a group of subcortical nuclei that are anatomically positioned to integrate cognitive, motor and sensorimotor inputs from the cortex. Amphetamines can differentially alter the functioning of specific BG circuits to produce neurochemical changes that affect cognition, movement, and drug seeking behavior thro...

  4. Cross-reactivity of stimulants found in sports drug testing by two fluorescence polarization immunoassays.

    Science.gov (United States)

    de la Torre, R; Badia, R; Gonzàlez, G; García, M; Pretel, M J; Farré, M; Segura, J

    1996-01-01

    We investigated the usefulness of immunological methods for presumptive detection of stimulants found in sports drug testing. The ingestion of substances that show no cross-reactivity in tests commercially available for the detection of amphetamines can produce positive results in the urine. Human metabolism contributes to the positive results of some urine samples when the parent compound does not cross-react with the antibodies of the assay. Urine samples from healthy volunteers given stimulants were tested by chromatographic methods and by two different fluorescence polarization immunoassays (FPIA) from Abbott Laboratories for the analysis of amphetamines. According to the results obtained, we classified stimulants into four groups: detectable stimulants that gave rise to amphetamine by human metabolism (group 1); detectable ephedrines and related compounds, appearing in the urine either as parent compounds or originated by metabolism (group 2); detectable stimulants that displayed actual cross-reactivity with amphetamine tests (group 3); and stimulants not detected by FPIA (group 4). Most of the true doping cases due to the ingestion of stimulants may be detected by FPIA. The specificity of the results may be increased by combining immunological assays with different antibodies.

  5. Misdiagnosed Pruritus; Formication due to Chronic Amphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Maryam Vahabzadeh

    2016-03-01

    Full Text Available Amphetamine abusers are shown to have significant cognitive impairments as well as delusional disorders. We present a 17-year-old man who was admitted to the toxicology emergency department with amphetamine overdose. Along with the classic signs and symptoms of overdose including mydriasis, tachycardia, hypertension, sweating and severe agitation, his urine toxicology screen test was found to be positive for 3,4-methylenedioxy-methamphetamine. In physical examination, widespread round-to-oval cutaneous lesions were observed all over his limbs and chest, notably the most easily reached sites of skin to be scratched. After regaining consciousness, the patient complained of pruritus and sensing the movement of insects under his skin. Further medical history showed that he had abused amphetamines for more than two years along with persistent pruritus, for which he had visited different physicians who mainly had made the diagnosis of allergy or dermatitis for him. He had been treated with antihistamines (hydroxyzine for a long period. He also had been diagnosed with scabies and treated with topical permethrin and lindane lotion. Despite receiving these treatments, he continued to have pruritus particularly on his forearms and hands. He was finally diagnosed with “Ekbom’s syndrome” and referred to psychological rehabilitation and psychosomatic outpatient clinic.

  6. 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.

  7. Automated identification of novel amphetamines using a pure neural network and neural networks coupled with principal component analysis

    Science.gov (United States)

    Gosav, S.; Praisler, M.; Dorohoi, D. O.; Popa, G.

    2005-06-01

    A pure neural network (NN) and several neural networks coupled with principal component analysis (PC-NN) have been developed in order to identify illicit amphetamines necessary in the investigation of drugs of abuse for epidemiological, clinical, and forensic purposes. The NN system has as input variables 260 spectral data, representing absorption intensities measured for each normalized infrared spectrum at 260 wavenumbers 10 cm -1 apart. In the case of PC-NN systems, the original spectral data (absorption intensities) have been compressed with the principal component analysis method (PCA), the scores of the principal components (PCs) being the inputs of these systems. We have built nine PC-NN systems, which have a different number of input variables: 3PCs, 4PCs, 5PCs, 6PCs, 7PCs, 8PCs, 9PCs, 10PCs and 15PCs. All systems are specialized to distinguish between stimulant amphetamines (class code M), hallucinogenic amphetamines (class code T) and nonamphetamines (class code N). We are now presenting a comparison of the validation results obtained for the NN system and for the best PC-NN system based on the scores of the first nine PCs (9PC-NN). The NN system correctly classifies all the positive samples, as opposed to the 9PC-NN system, which is characterized by a true positive rate (TP) of 90.91%. The true negative rate (TN) obtained for the first system (83.33%) is slightly higher than in the case of the later system (82.71%). Thus, the NN system is more sensitive and selective than the 9PC-NN system. We are also presenting a spectroscopic analysis of the false negative samples obtained in the case of 9PC-NN system.

  8. Amphetamine, cocaine and cannabinoids use among truck drivers on the roads in the State of Sao Paulo, Brazil.

    Science.gov (United States)

    Leyton, V; Sinagawa, D M; Oliveira, K C B G; Schmitz, W; Andreuccetti, G; De Martinis, B S; Yonamine, M; Munoz, D R

    2012-02-10

    Drugs are important risk factors for traffic accidents. In Brazil, truck drivers report using amphetamines to maintain their extensive work schedule and stay awake. These drugs can be obtained without prescription easily on Brazilian roads. The use of these stimulants can result in health problems and can be associated with traffic accidents. There are Brazilian studies that show that drivers use drugs. However, these studies are questionnaire-based and do not always reflect real-life situations. The purpose of this study was to demonstrate the prevalence of drug use by truck drivers on the roads of Sao Paulo State, Brazil, during 2009. Drivers of large trucks were randomly stopped by police officers on the interstate roads during morning hours. After being informed of the goals of the study, the drivers gave written informed consent before providing a urine sample. In addition, a questionnaire concerning sociodemographic characteristics and health information was administered. Urine samples were screened for amphetamines, cocaine, and cannabinoids by immunoassay and the confirmation was performed using gas chromatography-mass spectrometry (GC-MS). Of the 488 drivers stopped, 456 (93.4%) provided urine samples, and 9.3% of them (n=42) tested positive for drugs. Amphetamines were the most commonly found (n=26) drug, representing 61.9% of the positive samples. Ten cases tested positive for cocaine (23.8%), and five for cannabinoids (11.9%). All drivers were male with a mean age of 40 ± 10.8 years, and 29.3% of them reported some health problem (diabetes, high blood pressure and/or stress). A high incidence of truck drivers who tested positive for drug use was found, among other reported health problems. Thus, there is an evident need to promote a healthier lifestyle among professional drivers and a need for preventive measures aimed at controlling the use of drugs by truck drivers in Brazil.

  9. Performance-based testing for drugs of abuse: dose and time profiles of marijuana, amphetamine, alcohol, and diazepam.

    Science.gov (United States)

    Kelly, T H; Foltin, R W; Emurian, C S; Fischman, M W

    1993-09-01

    The time courses of the effects of acute doses of amphetamine (5 and 10 mg/70 kg), alcohol (0.3 and 0.6 g/kg), diazepam (5 and 10 mg/70 kg), and marijuana (2.0% and 3.5% delta 9-THC) on performance engendered by each of four computerized behavioral tasks were evaluated in six human subjects. These performance-based tasks have potential commercial utility for drug-use detection in the workplace. Alcohol and marijuana effects were reliably detected for up to three hours following dose administration with most procedures. Amphetamine and diazepam effects were also detected, but the dose effects and time courses were variable. The profile of behavioral effects varied across drugs, suggesting that performance-based testing procedures might be useful in discriminating which drug was administered and the time course of the drug's effects. Results indicate that repeated measurement with performance-based drug detection procedures can provide immediate indications of performance impairment in a cost-effective and noninvasive manner and, as such, would be a useful supplement to biological sample testing for drug-use detection.

  10. 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.

  11. Prescription Stimulants and the Development of Post-Traumatic Stress Disorder among U.S. Service Members

    Science.gov (United States)

    2013-08-13

    prescription stimulants were defined as a prescription for methylphenidate , dextroamphetamine, amphetamine, modafinil, armodafinil, methamphetamine...personal exposure to least one of the following: witnessing death, physical abuse , dead and/or decomposing bodies, maimed soldiers or civilians, or...stimulant initially prescribed was modafinil (n=99, 39%), followed by methylphenidate (n=83, 32%), dextroamphetamine (n=41, 16%), and other

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

    Science.gov (United States)

    Advokat, Claire

    2007-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

    Boer, S. de; Bohus, B.

    1990-01-01

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

  15. Effects of amphetamine and beta-endorphin fragments on maze performance in rats

    NARCIS (Netherlands)

    Bohus, B; de Boer, S.F.

    1990-01-01

    Fragments of beta-endorphin and amphetamine cause similar effects in some tests of maze behavior in rats. The present study served to compare the influence of amphetamine and two beta-endorphin fragments [beta-endorphin (beta E)-(2-9) and beta E-(2-16)] on maze behavior in more detail. In Experiment

  16. 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

    . 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...

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

    Science.gov (United States)

    2010-10-01

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

  18. 75 FR 69088 - Determination That Amphetamine Sulfate, 5 and 10 Milligram Tablets, Was Not Withdrawn From Sale...

    Science.gov (United States)

    2010-11-10

    ... HUMAN SERVICES Food and Drug Administration Determination That Amphetamine Sulfate, 5 and 10 Milligram... Amphetamine sulfate, 5 and 10 milligram (mg) tablets, was not withdrawn from sale for reasons of safety or... Amphetamine sulfate, 5 mg and 10 mg tablets, if all other legal and regulatory requirements are met....

  19. Methamphetamine, amphetamine, MDMA ('ecstasy'), MDA and mCPP modulate electrical and cholinergic input in PC12 cells.

    Science.gov (United States)

    Hondebrink, Laura; Meulenbelt, Jan; Rietjens, Saskia J; Meijer, Marieke; Westerink, Remco H S

    2012-03-01

    Reversal of the dopamine (DA) membrane transporter is the main mechanism through which many drugs of abuse increase DA levels. However, drug-induced modulation of exocytotic DA release by electrical (depolarization) and neurochemical inputs (e.g., acetylcholine (ACh)) may also contribute. We therefore investigated effects of methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and meta-chlorophenylpiperazine (mCPP) (1-1000 μM) on these inputs by measuring drug-induced changes in basal, depolarization- and ACh-evoked intracellular calcium concentrations ([Ca(2+)](i)) using a dopaminergic model (PC12 cells) and Fura 2 calcium imaging. The strongest drug-induced effects were observed on cholinergic input. At 0.1mM all drugs inhibited the ACh-evoked [Ca(2+)](i) increases by 40-75%, whereas ACh-evoked [Ca(2+)](i) increases were nearly abolished following higher drug exposure (1mM, 80-97% inhibition). Additionally, high MDMA and mCPP concentrations increased basal [Ca(2+)](i), but only following prior stimulation with ACh. Interestingly, low concentrations of methamphetamine or amphetamine (10 μM) potentiated ACh-evoked [Ca(2+)](i) increases. Depolarization-evoked [Ca(2+)](i) increases were also inhibited following exposure to high drug concentrations, although drugs were less potent on this endpoint. Our data demonstrate that at high drug concentrations all tested drugs reduce stimulation-evoked increases in [Ca(2+)](i), thereby probably reducing dopaminergic output through inhibition of electrical and cholinergic input. Furthermore, the increases in basal [Ca(2+)](i) at high concentrations of MDMA and mCPP likely increases dopaminergic output. Similarly, the increases in ACh-evoked [Ca(2+)](i) upon cholinergic stimulation following exposure to low concentrations of amphetamines can contribute to drug-induced increases in DA levels observed in vivo. Finally, this study shows that mCPP, which is regularly found in

  20. The pharmacology and clinical outcomes of amphetamines to treat ADHD: does composition matter?

    Science.gov (United States)

    Hodgkins, Paul; Shaw, Monica; McCarthy, Suzanne; Sallee, Floyd R

    2012-03-01

    Attention-deficit hyperactivity disorder (ADHD) treatment options include pharmacological and nonpharmacological approaches. In North America, psychostimulants (amphetamine and methylphenidate) are considered first-line pharmacological treatments for patients (children, adolescents and adults) with ADHD. However, in the UK, National Institute for Health and Clinical Excellence (NICE) guidelines have placed short-acting d-amphetamine as a third-line treatment option due to a lack of contemporary, published clinical trials on its efficacy and the concerns from clinical and patient experts regarding the potential for increased abuse and/or misuse compared with methylphenidate. These guidelines do not account for some of the more recent amphetamine products that have been developed to alleviate some of these concerns, but that are not currently approved in the UK or other European countries. The purpose of this review is to describe the pharmacology and clinical efficacy of various amphetamine compositions, as well as to explore the apparent differences in these compositions and their associated risks and benefits. A PubMed literature search was conducted to investigate amphetamine pharmacology, clinical efficacy and safety and ADHD outcomes in the published literature from 1980 through March 2011. Search terms included the keywords 'ADHD' or 'ADD' or 'hyperkinetic disorder' and any of the following keywords combined with 'or': 'amphetamine', 'dexamphetamine', 'mixed amphetamine salts', 'lisdexamfetamine' and 'methamphetamine'. The search included English-language primary research articles and review articles but excluded editorial articles and commentaries. The literature search resulted in 330 articles. Pertinent articles relating to amphetamine pharmacology, compositions, clinical efficacy and safety, effectiveness and tolerability, ADHD outcomes and abuse liability were included in this review. The different delivery profiles of amphetamine compositions result in

  1. 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.

  2. Raman Optical Activity and Raman Spectra of Amphetamine Species

    DEFF Research Database (Denmark)

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

    2012-01-01

    are employed for identification purposes. The DFT calculations show that the most stable conformations are those allowing for close contact between the aromatic ring and the amine hydrogen atoms. The internal rotational barrier within the same amphetamine enanti- omer has a considerable influence on the Raman......-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....

  3. The discriminative stimulus effects of midazolam are resistant to modulation by morphine, amphetamine, dizocilpine and γ-butyrolactone in rhesus monkeys

    Science.gov (United States)

    Bai, Xiang; France, Charles P.; Gerak, Lisa R.

    2011-01-01

    Rationale Although abuse of benzodiazepines alone is uncommon, it is high in polydrug abusers, including those who abuse primarily opioids or stimulants. Objectives This study investigated whether drugs that are abused (e.g., amphetamine) or have mechanisms of action similar to abused drugs (e.g., morphine) alter the discriminative stimulus effects of the benzodiazepine midazolam. Methods Three rhesus monkeys discriminated 0.56 mg/kg of midazolam while responding under a fixed ratio 10 schedule of food presentation. Dose-effect curves were determined for midazolam alone and in the presence of morphine (opioid receptor agonist), amphetamine (dopamine receptor indirect agonist), dizocilpine (N-methyl-D-aspartic acid receptor antagonist), or γ-butyrolactone (prodrug of γ-hydroxybutyrate, which acts primarily at GABAB receptors). Results Doses of midazolam larger than 0.32 mg/kg produced ≥80% midazolam-lever responding. When administered alone, morphine, amphetamine, dizocilpine and γ-butyrolactone did not produce midazolam-lever responding, although large doses of each drug eliminated responding; when administered in combination with midazolam, they did not alter the discriminative stimulus effects of midazolam up to doses that markedly decreased response rates. Conclusions The current study demonstrates a lack of modulation of the discriminative stimulus effects of midazolam by morphine, amphetamine, dizocilpine, and γ-butyrolactone. Other effects of benzodiazepines, such as their reinforcing effects, might be altered by these other drugs, or benzodiazepines might modulate the discriminative stimulus or reinforcing effects of the other drugs, which might contribute to the relatively high incidence of benzodiazepine abuse among polydrug abusers. PMID:21503606

  4. Amphetamine withdrawal differentially affects hippocampal and peripheral corticosterone levels in response to stress.

    Science.gov (United States)

    Bray, Brenna; Scholl, Jamie L; Tu, Wenyu; Watt, Michael J; Renner, Kenneth J; Forster, Gina L

    2016-08-01

    Amphetamine withdrawal is associated with heightened anxiety-like behavior, which is directly driven by blunted stress-induced glucocorticoid receptor-dependent serotonin release in the ventral hippocampus. This suggests that glucocorticoid availability in the ventral hippocampus during stress may be reduced during amphetamine withdrawal. Therefore, we tested whether amphetamine withdrawal alters either peripheral or hippocampal corticosterone stress responses. Adult male rats received amphetamine (2.5mg/kg, ip) or saline for 14 days followed by 2 weeks of withdrawal. Contrary to our prediction, microdialysis samples from freely-moving rats revealed that restraint stress-induced corticosterone levels in the ventral hippocampus are enhanced by amphetamine withdrawal relative to controls. In separate groups of rats, plasma corticosterone levels increased immediately after 20min of restraint and decreased to below stress-naïve levels after 1h, indicating negative feedback regulation of corticosterone following stress. However, plasma corticosterone responses were similar in amphetamine-withdrawn and control rats. Neither amphetamine nor stress exposure significantly altered protein expression or enzyme activity of the steroidogenic enzymes 11β-hydroxysteroid dehydrogenase (11β-HSD1) or hexose-6-phosphate dehydrogenase (H6PD) in the ventral hippocampus. Our findings demonstrate for the first time that amphetamine withdrawal potentiates stress-induced corticosterone in the ventral hippocampus, which may contribute to increased behavioral stress sensitivity previously observed during amphetamine withdrawal. However, this is not mediated by either changes in plasma corticosterone or hippocampal steroidogenic enzymes. Establishing enhanced ventral hippocampal corticosterone as a direct cause of greater stress sensitivity may identify the glucocorticoid system as a novel target for treating behavioral symptoms of amphetamine withdrawal. Copyright © 2016 Elsevier B

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-04-25

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

  6. Dimethylamylamine: a drug causing positive immunoassay results for amphetamines.

    Science.gov (United States)

    Vorce, Shawn P; Holler, Justin M; Cawrse, Brian M; Magluilo, Joseph

    2011-04-01

    The Department of Defense (DoD) operates six forensic urine drug-testing laboratories that screen close to 5 million urine samples for amphetamines yearly. Recently, the DoD laboratories have observed a significant decrease in the confirmation rates for amphetamines because of specimens screening positive by two separate immunoassays and confirming negative by gas chromatography-mass spectrometry (GC-MS). Previous studies conducted by the Division of Forensic Toxicology, Armed Force Institute of Pathology (AFIP) utilizing a GC-MS basic drug screen and a designer drug screen revealed no common compound or compound classes as to the cause of the immunoassay-positive results. Additional information obtained from an immunoassay vendor suggested the anorectic compound dimethylamylamine (DMAA) may be the cause of the false-positive screens. An additional 134 false-positive samples were received and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS-MS) for DMAA. LC-MS-MS analysis revealed the presence of DMAA in 92.3% of the false-positive samples at a concentration of approximately 6.0 mg/L DMAA, causing a positive screen on both immunoassay kits.

  7. Miniaturized sample preparation method for determination of amphetamines in urine.

    Science.gov (United States)

    Nishida, Manami; Namera, Akira; Yashiki, Mikio; Kimura, Kojiro

    2004-07-16

    A simple and miniaturized sample preparation method for determination of amphetamines in urine was developed using on-column derivatization and gas chromatography-mass spectrometry (GC-MS). Urine was directly applied to the extraction column that was pre-packed with Extrelut and sodium carbonate. Amphetamine (AP) and methamphetamine (MA) in urine were adsorbed on the surface of Extrelut. AP and MA were then converted to a free base and derivatized to N-propoxycarbonyl derivatives using propylchloroformate on the column. Pentadeuterated MA was used as an internal standard. The recoveries of AP and MA from urine were 100 and 102%, respectively. The calibration curves showed linearity in the range of 0.50-50 microg/mL for AP and MA in urine. When urine samples containing two different concentrations (0.50 and 5.0 microg/mL) of AP and MA were determined, the intra-day and inter-day coefficients of variation were 1.4-7.7%. This method was applied to 14 medico-legal cases of MA intoxication. The results were compared and a good agreement was obtained with a HPLC method.

  8. 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.

  9. The trazodone metabolite meta-chlorophenylpiperazine can cause false-positive urine amphetamine immunoassay results.

    Science.gov (United States)

    Baron, Jason M; Griggs, David A; Nixon, Andrea L; Long, William H; Flood, James G

    2011-07-01

    Amphetamines and methamphetamines are part of an important class of drugs included in most urine drugs of abuse screening panels, and a common assay to detect these drugs is the Amphetamines II immunoassay (Roche Diagnostics). To demonstrate that meta-chlorophenylpiperazine (m-CPP), a trazodone metabolite, cross-reacts in the Amphetamines II assay, we tested reference standards of m-CPP at various concentrations (200 to 20,000 g/L). We also tested real patient urine samples containing m-CPP (detected and quantified by HPLC) with no detectable amphetamine, methamphetamine, or MDMA (demonstrated by GC MS). In both the m-CPP standards and the patient urine samples, we found a strong association between m-CPP concentration and Amphetamines II immunoreactivity (r = 0.990 for the urine samples). Further, we found that patients taking trazodone can produce urine with sufficient m-CPP to result in false-positive Amphetamines II results. At our institution, false-positive amphetamine results occur not infrequently in patients taking trazodone with at least 8 trazodone-associated false-positive results during a single 26-day period. Laboratories should remain cognizant of this interference when interpreting results of this assay.

  10. Repeat-until-success quantum repeaters

    Science.gov (United States)

    Bruschi, David Edward; Barlow, Thomas M.; Razavi, Mohsen; Beige, Almut

    2014-09-01

    We propose a repeat-until-success protocol to improve the performance of probabilistic quantum repeaters. Conventionally, these rely on passive static linear-optics elements and photodetectors to perform Bell-state measurements (BSMs) with a maximum success rate of 50%. This is a strong impediment for entanglement swapping between distant quantum memories. Every time a BSM fails, entanglement needs to be redistributed between the corresponding memories in the repeater link. The key ingredients of our scheme are repeatable BSMs. Under ideal conditions, these turn probabilistic quantum repeaters into deterministic ones. Under realistic conditions, our protocol too might fail. However, using additional threshold detectors now allows us to improve the entanglement generation rate by almost orders of magnitude, at a nominal distance of 1000 km, compared to schemes that rely on conventional BSMs. This improvement is sufficient to make the performance of our scheme comparable to the expected performance of some deterministic quantum repeaters.

  11. 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…

  12. 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.

  13. PI3K signaling supports amphetamine-induced dopamine efflux.

    Science.gov (United States)

    Lute, Brandon J; Khoshbouei, Habibeh; Saunders, Christine; Sen, Namita; Lin, Richard Z; Javitch, Jonathan A; Galli, Aurelio

    2008-08-01

    The dopamine (DA) transporter (DAT) is a major molecular target of the psychostimulant amphetamine (AMPH). AMPH, as a result of its ability to reverse DAT-mediated inward transport of DA, induces DA efflux thereby increasing extracellular DA levels. This increase is thought to underlie the behavioral effects of AMPH. We have demonstrated previously that insulin, through phosphatidylinositol 3-kinase (PI3K) signaling, regulates DA clearance by fine-tuning DAT plasma membrane expression. PI3K signaling may represent a novel mechanism for regulating DA efflux evoked by AMPH, since only active DAT at the plasma membrane can efflux DA. Here, we show in both a heterologous expression system and DA neurons that inhibition of PI3K decreases DAT cell surface expression and, as a consequence, AMPH-induced DA efflux.

  14. The shapes of neurotransmitters by millimetrewave spectroscopy: amphetamine

    Science.gov (United States)

    Godfrey, Peter D.; McGlone, Shane J.; Brown, Ronald D.

    2001-12-01

    We have studied the amphetamine molecule both experimentally by rotational spectroscopy and theoretically by ab initio molecular orbital calculations at the MP2/6-31G(d,p) level. Two species x and y of amphetamine detected by millimetre wave argon free jet expansion spectroscopy are identifiable from values of their rotational constants together with the quadrupole hyperfine patterns of some spectral lines. The more abundant conformer x is amp(1) and the less abundant y is amp(2) corresponding to the theoretical conformers I and II [see Fig. 2]. The identity of conformer x as amp(1) is supported by amino-hydrogen coordinate data obtained from detection of the N-deutero isotopomer of this conformer. Both amp(1) and amp(2) appear to be stabilized by non-classical hydrogen bonds from an amino hydrogen to the aromatic π-electron cloud, and have the methyl group trans to the phenyl substituent. Calculations of the relative energies of the conformers at the MP2/6-31 G(d,p) level suggest that the corresponding gauche-methyl conformers V and VI may be of energy similar to II. However, calculations of details of the potential energy surface at levels of theory higher than that used in the present work will be needed to clarify this question. By analogy with smaller disubstituted ethanes, we would expect the barriers to rotation about the C-C bond to be too high to enable relaxation of one conformer to another during the jet expansion.

  15. Differential Effect of Amphetamine Optical Isomers on Bender Gestalt Performance of the Minimally Brain Dysfunctioned

    Science.gov (United States)

    Arnold, L. Eugene; And Others

    1978-01-01

    The differential effect of amphetamine optical isomers on Bender Gestalt performance was examined in 31 hyperkinetic minimally brain dysfunctioned children between the ages of 4 and 12 years, using a double-blind Latin-square crossover comparison. (Author)

  16. 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...... terminus in mediating the action of amphetamines by focusing initially on the highly conserved threonine residue at position 81, a candidate site for phosphorylation by protein kinase C. Molecular dynamics simulations of the wild type SERT, compared with its mutations SERT(T81A) and SERT(T81D), suggested......, SERT(T81A) (and the homologous mutations in noradrenaline and dopamine) failed to support amphetamine-induced efflux, and this was not remedied by aspartate at this position. Amphetamine-induced currents through SERT(T81A) were comparable with those through the wild type transporter. Both abundant Na...

  17. 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.

  18. In vivo amphetamine action is contingent on αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Mus, Liudmilla; Eisenrauch, Birgit

    2014-01-01

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

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

    OpenAIRE

    J Gordon Millichap

    2009-01-01

    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.

  20. Antipsychotic pathway genes with expression altered in opposite direction by antipsychotics and amphetamine.

    Science.gov (United States)

    Ko, Françoise; Tallerico, Teresa; Seeman, Philip

    2006-08-01

    To develop a new strategy for identifying possible psychotic- or antipsychotic-related pathway genes, rats were treated with clinical doses of haloperidol and clozapine for 4 days, and the altered expression of genes was compared with the genes altered in expression after amphetamine sensitization. The objective was to identify genes with expression altered in the same direction by haloperidol and clozapine but in the opposite direction in the amphetamine-sensitized rat striatum. These criteria were met by 21 genes, consisting of 15 genes upregulated by amphetamine, and 6 genes downregulated by amphetamine. Of the 21 genes, 15 are not presently identified, and only 3 genes (cathepsin K, GRK6, and a gene with accession number AI177589) are located in chromosome regions known to be associated with schizophrenia.

  1. Case Reports of Aripiprazole Causing False-Positive Urine Amphetamine Drug Screens in Children.

    Science.gov (United States)

    Kaplan, Justin; Shah, Pooja; Faley, Brian; Siegel, Mark E

    2015-12-01

    Urine drug screens (UDSs) are used to identify the presence of certain medications. One limitation of UDSs is the potential for false-positive results caused by cross-reactivity with other substances. Amphetamines have an extensive list of cross-reacting medications. The literature contains reports of false-positive amphetamine UDSs with multiple antidepressants and antipsychotics. We present 2 cases of presumed false-positive UDSs for amphetamines after ingestion of aripiprazole. Case 1 was a 16-month-old girl who accidently ingested 15 to 45 mg of aripiprazole. She was lethargic and ataxic at home with 1 episode of vomiting containing no identifiable tablets. She remained sluggish with periods of irritability and was admitted for observation. UDS on 2 consecutive days came back positive for amphetamines. Case 2 was of a 20-month-old girl who was brought into the hospital after accidental ingestion of an unknown quantity of her father's medications which included aripiprazole. UDS on the first day of admission came back positive only for amphetamines. Confirmatory testing with gas chromatography-mass spectrometry (GC-MS) on the blood and urine samples were also performed for both patients on presentation to detect amphetamines and were subsequently negative. Both patients returned to baseline and were discharged from the hospital. To our knowledge, these cases represent the first reports of false-positive amphetamine urine drug tests with aripiprazole. In both cases, aripiprazole was the drug with the highest likelihood of causing the positive amphetamine screen. The implications of these false-positives include the possibility of unnecessary treatment and monitoring of patients.

  2. Frequency of False Positive Amphetamine Screens due to Bupropion Using the Syva Emit II Immunoassay

    OpenAIRE

    Casey, Erica R; Scott, Mitchell G.; Tang, Schirin; Mullins, Michael E.

    2010-01-01

    Bupropion is a commonly prescribed, monocyclic antidepressant often used as an aid for smoking cessation. Several case reports have described false positive amphetamine urine drug screens (UDS) associated with bupropion. We sought to determine whether false positive amphetamine UDS due to the use of bupropion would be a frequent occurrence. We conducted an IRB-approved, retrospective chart review of all emergency department patients who underwent UDS between 1 January 2006 and 31 July 2007. A...

  3. Methamphetamine and Amphetamine Isomer Concentrations in Human Urine Following Controlled Vicks VapoInhaler Administration

    OpenAIRE

    Smith, Michael L.; Nichols, Daniel C.; Underwood, Paula; Fuller, Zachary; Moser, Matthew A.; Flegel, Ron; Gorelick, David A.; Newmeyer, Matthew N.; Concheiro, Marta; HUESTIS, MARILYN A.

    2014-01-01

    Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography–mass spectrometry (GC–MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended do...

  4. Use of amphetamines to improve the academic performance in students of the University of Manizales, 2008

    OpenAIRE

    Acevedo Urrego, Marcela; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Arango Orozco, Lisa; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Blandón Montoya, Liliana; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Buelvas Soto, Liz; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Carmona Velasquez, Daybeth Vanesa; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Castaño Castrillón, Jose Jaime; Profesor Titular, Director Centro de Investigaciones, Facultad de Medicina, Universidad de Manizales. Cra 9 # 19-03, Manizales, Caldas, Colombia. Correo electrónico .; Castro Rocha, Betsy Carolina; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Serna, Juan Camilo; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Trujillo Sandoval, Karol Susana; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Arango, César; Docente Pediatría Facultad de Medicina, Universidad de Manizales Remitido para publicación: 16-02-2009. Aprobado para publicación: 11-03-2009

    2009-01-01

    Objective: Identify the frequency of use of non-medicated amphetamines and othersubstances to improve academic performance in students of the University of Manizales(Manizales, Colombia).Materials and methods: A cross sectional study was realized. The population was of3616 students of all the faculties of the University of Manizales, with a representativesample of 309 students. An anonymous sur5vey was made in order to collect informationwhich allowed to identify the consumption of amphetamin...

  5. 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.

  6. Evaluation of ephedrine, pseudoephedrine and phenylpropanolamine concentrations in human urine samples and a comparison of the specificity of DRI amphetamines and Abuscreen online (KIMS) amphetamines screening immunoassays.

    Science.gov (United States)

    Stout, Peter R; Klette, Kevin L; Horn, Carl K

    2004-01-01

    The purpose of this study was to evaluate the ability of two amphetamine class screening reagents to exclude ephedrine (EPH), pseudoephedrine (PSEPH), and phenylpropanolamine (PPA) from falsely producing positive immunoassay screening results. The study also sought to characterize the prevalence and concentration distributions of EPH, PSEPH, and PPA in samples that produced positive amphetamine screening results. Approximately 27,400 randomly collected human urine samples from Navy and Marine Corps members were simultaneously screened for amphetamines using the DRI and Abuscreen online immunoassays at a cutoff concentration of 500 ng/mL. All samples that screened positive were confirmed for amphetamine (AMP), methamphetamine (MTH), 3,4-Methylenedioxyamphetamine (MDA), 3,4-Methylenedioxymethamphetamine (MDMA), EPH, PSEPH, and PPA by gas chromatography/mass spectrometry (GC/MS). The DRI AMP immunoassay identified 1,104 presumptive amphetamine positive samples, of which only 1.99% confirmed positive for the presence of AMP, MTH, MDA, or MDMA. In contrast, the online AMP reagent identified 317 presumptive amphetamine positives with a confirmation rate for AMP, MTH, MDA, or MDMA of 7.94%. The presence of EPH, PSEPH, or PPA was confirmed in 833 of the 1,104 samples that failed to confirm positive for AMP, MTH, MDA, or MDMA; all of the 833 samples contained PSEPH. When compared to the entire screened sample set, PSEPH was present in approximately 3%, EPH in 0.9%, and PPA in 0.8% of the samples. The results indicate that cross reactivities for EPH, PSEPH, and PPA are greater than reported by the manufacturer of these reagents. The distribution of concentrations indicates that very large concentrations of EPH, PSEPH, and PPA are common.

  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. Comparison of the sensitivity and specificity of six immunoassays for the detection of amphetamines in urine.

    Science.gov (United States)

    Verstraete, Alain G; Heyden, Fien V

    2005-01-01

    We analyzed 225 urine samples with FPIA (Abbott Amphetamine/Methamphetamine II on ADx and AxSYM), EMIT (Emit II Plus Monoclonal Amphetamine/Metamphetamine assay and EMIT II Plus Amphetamines assay, EMIT N), and KIMS (standard protocol and MDMA protocol, KIMS and KIMS X, respectively) immunoassays and compared their sensitivity and specificity. All assays were calibrated and used semi-quantitatively. All samples that screened positive by any amphetamine screening method and 15% of the negative samples were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS-MS). A sample was considered positive for amphetamines if amphetamine, methamphetamine, methylenedioxymethamphetamine, methylenedio-xyethylamphetamine, or methylenedioxyamphetamine was present at 250 ng/mL. Ninety (40%) of the samples were positive by LC-MS-MS. The areas under the receiver operating characteristic curve varied between 0.972 (KIMS X) and 1.000 (ADx). The optimal cut-off concentrations varied between 271 ng/mL (EMIT N) and 723 ng/mL (AxSYM). The sensitivity was 100% for ADx and between 93 and 95% for the other assays. The specificity varied between 88% (KIMS) and 100% (EMIT N). Use of a 500 ng/mL screening cut-off would have resulted in identical or very similar results for ADx and KIMS X and large increases in the false positives for AxSYM and EMIT and the false negatives for EMIT N and KIMS.

  9. Food consumption and weight gain after cessation of chronic amphetamine administration.

    Science.gov (United States)

    Orsini, Caitlin A; Ginton, Guy; Shimp, Kristy G; Avena, Nicole M; Gold, Mark S; Setlow, Barry

    2014-07-01

    Cessation of drug use often coincides with increased food consumption and weight gain in recovering addicts. However, it is not known whether this phenomenon (particularly the weight gain) is uniquely human, or whether it represents a consequence of drug cessation common across species. To address this issue, rats (n = 10/group) were given systemic injections of D-amphetamine (3 mg/kg) or an equal volume of saline vehicle for 9 consecutive days. Beginning 2 days after the final injection, rats were given free access to a highly palatable food mixture (consisting of sugar and butter) along with their standard chow diet, and food consumption and body weight were measured every 48 h for 30 days. Consistent with clinical observations, amphetamine-treated rats showed a greater increase in body weight over the course of the 30 days relative to vehicle-treated rats. Surprisingly, there was no difference in highly palatable food consumption between amphetamine- and vehicle-treated groups, but the amphetamine-treated group consumed significantly more standard chow than the control group. The finding that a history of chronic amphetamine exposure increases food consumption is consistent with previous work in humans showing that withdrawal from drugs of abuse is associated with overeating and weight gain. The current findings may reflect amphetamine-induced sensitization of mechanisms involved in reward motivation, suggesting that weight gain following drug cessation in humans could be due to similar mechanisms.

  10. Amphetamine affects the behavioral outcome of lateral fluid percussion brain injury in the rat.

    Science.gov (United States)

    Prasad, R M; Dose, J M; Dhillon, H S; Carbary, T; Kraemer, P J

    1995-01-01

    This study examined the effects of (D)-amphetamine, methoxamine (an al-adrenergic receptor agonist), and prazosin (an al-adrenergic receptor antagonist) on the behavioral outcome of lateral fluid percussion brain injury. Rats trained to perform a beam walking task were subjected to brain injury of moderate severity (2.1-2.2 atm). At 10 min after injury, rats were treated with amphetamine, methoxamine or prazosin at two different dose levels. Amphetamine-treated animals displayed significantly lower impairment in beam walking ability from days 1 to 5 after brain injury. Neither methoxamine nor prazosin significantly affected the impairment in beam walking ability from day 1 to day 7 after injury. However, prazosin treatment at both dose levels increased the post-injury mortality and the incidences of failure to recovery from hemiplegia. Amphetamine-treatment at 4 mg/kg, but not at 2 mg/kg, improved the spatial learning abilities of the injured animals. Neither methoxamine nor prazosin affected the spatial learning abilities. These results indicate that amphetamine facilitated beam walking recovery and improved cognitive function after concussive fluid percussion injury. Although the methoxamine experiments suggest that the norepinephrine-α1-adrenergic receptor system may not be involved in the pathophysiology of fluid percussion brain injury, our results with amphetamine (beneficial effects) and prazosin (deleterious effects) and the results observed in other models of brain injury point out that further investigations are necessary to understand the role of a1-adrenergic receptors in brain injury.

  11. Amphetamine and methamphetamine induced psychosis: toxicological findings, comparison with acute symptoms of schizophrenia and transition of diagnoses. A clinical investigation

    OpenAIRE

    Medhus, Sigrid

    2014-01-01

    Background: There is a long-standing debate about the relationship between amphetamines and psychoses. While some have found psychoses induced by amphetamines to be indistinguishable from schizophrenia, others have found that psychoses induced by amphetamines, in contrast to schizophrenia, were characterized by visual hallucinations and lack of thought disorder. It has also been discusses whether there really are sharp boundaries between the two diagnoses, and whether there is a transition be...

  12. Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism.

    Science.gov (United States)

    Moy, Sheryl S; Riddick, Natallia V; Nikolova, Viktoriya D; Teng, Brian L; Agster, Kara L; Nonneman, Randal J; Young, Nancy B; Baker, Lorinda K; Nadler, Jessica J; Bodfish, James W

    2014-02-01

    Restricted repetitive behaviors are core symptoms of autism spectrum disorders (ASDs). The range of symptoms encompassed by the repetitive behavior domain includes lower-order stereotypy and self-injury, and higher-order indices of circumscribed interests and cognitive rigidity. Heterogeneity in clinical ASD profiles suggests that specific manifestations of repetitive behavior reflect differential neuropathology. The present studies utilized a set of phenotyping tasks to determine a repetitive behavior profile for the C58/J mouse strain, a model of ASD core symptoms. In an observational screen, C58/J demonstrated overt motor stereotypy, but not over-grooming, a commonly-used measure for mouse repetitive behavior. Amphetamine did not exacerbate motor stereotypy, but had enhanced stimulant effects on locomotion and rearing in C58/J, compared to C57BL/6J. Both C58/J and Grin1 knockdown mice, another model of ASD-like behavior, had marked deficits in marble-burying. In a nose poke task for higher-order repetitive behavior, C58/J had reduced holeboard exploration and preference for non-social, versus social, olfactory stimuli, but did not demonstrate cognitive rigidity following familiarization to an appetitive stimulus. Analysis of available high-density genotype data indicated specific regions of divergence between C58/J and two highly-sociable strains with common genetic lineage. Strain genome comparisons identified autism candidate genes, including Cntnap2 and Slc6a4, located within regions divergent in C58/J. However, Grin1, Nlgn1, Sapap3, and Slitrk5, genes linked to repetitive over-grooming, were not in regions of divergence. These studies suggest that specific repetitive phenotypes can be used to distinguish ASD mouse models, with implications for divergent underlying mechanisms for different repetitive behavior profiles.

  13. A Preliminary Investigation of Individual Differences in Subjective Responses to D-Amphetamine, Alcohol, and Delta-9-Tetrahydrocannabinol Using a Within-Subjects Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Margaret C Wardle

    Full Text Available Polydrug use is common, and might occur because certain individuals experience positive effects from several different drugs during early stages of use. This study examined individual differences in subjective responses to single oral doses of d-amphetamine, alcohol, and delta-9-tetrahydrocannabinol (THC in healthy social drinkers. Each of these drugs produces feelings of well-being in at least some individuals, and we hypothesized that subjective responses to these drugs would be positively correlated. We also examined participants' drug responses in relation to personality traits associated with drug use. In this initial, exploratory study, 24 healthy, light drug users (12 male, 12 female, aged 21-31 years, participated in a fully within-subject, randomized, counterbalanced design with six 5.5-hour sessions in which they received d-amphetamine (20mg, alcohol (0.8 g/kg, or THC (7.5 mg, each paired with a placebo session. Participants rated the drugs' effects on both global measures (e.g. feeling a drug effect at all and drug-specific measures. In general, participants' responses to the three drugs were unrelated. Unexpectedly, "wanting more" alcohol was inversely correlated with "wanting more" THC. Additionally, in women, but not in men, "disliking" alcohol was negatively correlated with "disliking" THC. Positive alcohol and amphetamine responses were related, but only in individuals who experienced a stimulant effect of alcohol. Finally, high trait constraint (or lack of impulsivity was associated with lower reports of liking alcohol. No personality traits predicted responses across multiple drug types. Generally, these findings do not support the idea that certain individuals experience greater positive effects across multiple drug classes, but instead provide some evidence for a "drug of choice" model, in which individuals respond positively to certain classes of drugs that share similar subjective effects, and dislike other types

  14. Does COMT genotype influence the effects of d-amphetamine on executive functioning?

    Science.gov (United States)

    Wardle, M C; Hart, A B; Palmer, A A; de Wit, H

    2013-02-01

    In a widely cited study, Mattay et al. reported that amphetamine (0.25 mg/kg oral, or 17 mg for a 68 kg individual) impaired behavioral and brain indices of executive functioning, measured using the Wisconsin Card Sorting Task (WCST) and N-Back working memory task, in 6 individuals homozygous for the met allele of the val158met polymorphism in the catechol-O-methyltransferase (COMT) gene, whereas it improved executive functioning in 10 individuals homozygous for the more active val allele. We attempted to replicate their behavioral findings in a larger sample, using similar executive functioning tasks and a broader range of amphetamine doses. Over four sessions, n = 200 healthy normal adults received oral placebo, d-amphetamine 5, 10, and 20 mg (average of 0.07, 0.15 and 0.29 mg/kg), under counterbalanced double-blind conditions and completed WCST and N-back tests of executive functioning. Amphetamine had typical effects on blood pressure and processing speed but did not affect executive functioning. COMT genotype (val158met) was not related to executive functioning under placebo or amphetamine conditions, even when we compared only the homozygous val/val and met/met genotypes at the highest dose of amphetamine (20 mg). Thus, we were not able to replicate the behavioral interaction between COMT and amphetamine seen in Mattay et al. We discuss possible differences between the studies and the implications of our findings for the use of COMT genotyping to predict clinical responses to dopaminergic drugs, and the use of intermediate phenotypes in genetic research.

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

    Science.gov (United States)

    McKenna, Stacey A

    2011-11-01

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

  16. Response of CEDIA amphetamines assay after a single dose of bitter orange.

    Science.gov (United States)

    Nguyen, DiemThuy T; Bui, Linda T; Ambrose, Peter J

    2006-04-01

    Bitter orange has recently been substituted as an ingredient in many "ephedra-free" dietary supplements used for weight loss. The primary active ingredient in bitter orange is synephrine. Previous reports have documented false-positive results from ephedrine with urine amphetamine assays. Because of the similarity in chemical structure of ephedrine and synephrine, it is hypothesized that ingestion of a bitter orange supplement may have the potential to cause false-positive results with urine amphetamine assays. The purpose of this study was to determine the response of the CEDIA Amphetamines Assay after ingestion of bitter orange. Six healthy adult male volunteers were administered a single oral dose of Nature's Way Bitter Orange, a 900-mg dietary supplement extract standardized to 6% synephrine. Urine specimens were collected at baseline and 3 and 6 hours post-administration. Additional urine specimens were collected from 1 subject at 9, 12, and 15 hours after administration. All specimens were analyzed by the CEDIA Amphetamines Assay. Urine specific gravity and pH also were measured. All urine specimens demonstrated a negative response to the CEDIA Amphetamines Assay. Urine specific gravity ranged from 1.007 to 1.028, and pH ranged from 5.0 to 7.0; thus, reducing the possibility that the negative results were caused by diluted specimens or reduced excretion of synephrine into alkaline urine. This information will be of value when health care providers or those who interpret drug screens are asked to provide consultation regarding the interference of bitter orange supplements with the CEDIA Amphetamines Assay. A single-dose of Nature's Way Bitter Orange was not found to cause a false-positive response to the CEDIA Amphetamines Assay in 6 healthy adult male volunteers.

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

    Science.gov (United States)

    Sucic, Sonja; Dallinger, Stefan; Zdrazil, Barbara; Weissensteiner, René; Jørgensen, Trine N; Holy, Marion; Kudlacek, Oliver; Seidel, Stefan; Cha, Joo Hwan; Gether, Ulrik; Newman, Amy H; Ecker, Gerhard F; Freissmuth, Michael; Sitte, Harald H

    2010-04-02

    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 terminus in mediating the action of amphetamines by focusing initially on the highly conserved threonine residue at position 81, a candidate site for phosphorylation by protein kinase C. Molecular dynamics simulations of the wild type SERT, compared with its mutations SERT(T81A) and SERT(T81D), suggested structural changes in the inner vestibule indicative of an opening of the inner vestibule. Predictions from this model (e.g. the preferential accumulation of SERT(T81A) in the inward conformation, its reduced turnover number, and a larger distance between its N and C termini) were verified. Most importantly, SERT(T81A) (and the homologous mutations in noradrenaline and dopamine) failed to support amphetamine-induced efflux, and this was not remedied by aspartate at this position. Amphetamine-induced currents through SERT(T81A) were comparable with those through the wild type transporter. Both abundant Na(+) entry and accumulation of SERT(T81A) in the inward facing conformation ought to favor amphetamine-induced efflux. Thus, we surmised that the N terminus must play a direct role in driving the transporter into a state that supports amphetamine-induced efflux. This hypothesis was verified by truncating the first 64 amino acids and by tethering the N terminus to an additional transmembrane helix. Either modification abolished amphetamine-induced efflux. We therefore conclude that the N terminus of monoamine transporters acts as a lever that sustains reverse transport.

  18. Development and evaluation of an improved method for screening of amphetamines.

    Science.gov (United States)

    Shindelman, J; Mahal, J; Hemphill, G; Pizzo, P; Coty, W A

    1999-10-01

    We developed a homogeneous immunoassay method to eliminate false-positive amphetamine results caused by cross-reactive substances, including over-the-counter allergy and cold medications. This method uses a neutralizing antibody that binds to amphetamines but does not bind to the labeled amphetamine conjugate used in the assay. The amount of neutralizing antibody is sufficient to reduce the assay signal resulting from authentic amphetamine and methamphetamine, but not the signal resulting from cross-reactants. This concept was implemented using the CEDIA DAU Amphetamines assay on Hitachi 747 and 717 clinical chemistry analyzers. Urine samples were tested using the standard, unmodified reagents in one channel and reagents containing the neutralizing antibody in a second channel. The difference in rate between the two tests was calculated by the analyzer; true-positive samples showed a significantly greater decrease in assay signal in response to neutralizing antibody as compared with false-positive samples. The neutralization method was evaluated in two studies using 448 samples that tested positive in the initial CEDIA DAU Amphetamines screening test. The samples were separated into categories of 154 true-positive samples and 294 false-positive samples based upon a secondary screen with the Abbott FPIA Amphetamines assay followed by gas chromatography-mass spectrometry (GC-MS) testing using the HHS (SAMHSA) cutoff criteria. The CEDIA neutralization test successfully identified all 154 of the GC-MS confirmed positive samples. The test successfully identified as false positive 251 out of the 294 (85.4%) samples that failed to confirm by GC-MS.

  19. Effects of amphetamine on pro-social ultrasonic communication in juvenile rats: Implications for mania models.

    Science.gov (United States)

    Engelhardt, K-Alexander; Fuchs, Eberhard; Schwarting, Rainer K W; Wöhr, Markus

    2017-03-01

    Communication is the act of information transfer between sender and receiver. In rats, vocal communication can be studied through ultrasonic vocalizations (USV). 50-kHz USV occur in appetitive situations, most notably juvenile play, likely expressing the sender׳s positive affective state. Such appetitive 50-kHz USV serve important pro-social communicative functions and elicit social exploratory and approach behavior in the receiver. Emission of 50-kHz USV can be induced pharmacologically by the administration of psychostimulant drugs, such as amphetamine. However, it is unknown whether amphetamine affects the pro-social communicative function of 50-kHz USV in the receiver. We therefore assessed dose-response effects of amphetamine (0.0mg/kg, 0.5mg/kg, 1.0mg/kg, 2.5mg/kg, 5.0mg/kg) on pro-social ultrasonic communication on both, sender and receiver, in juvenile rats. We found an inverted U-shaped effect of amphetamine on 50-kHz USV emission, with 50-kHz USV levels being strongly enhanced by moderate doses, yet less prominent effects were seen following the highest dose. Likewise, amphetamine exerted inverted U-shaped effects on social exploratory and approach behavior induced by playback of appetitive 50-kHz USV. Social approach was enhanced by moderate amphetamine doses, but completely abolished following the highest dose. Amphetamine further dose-dependently promoted the emission of 50-kHz USV following playback of appetitive 50-kHz USV, indicating more vigorous attempts to establish social proximity. Our results support an important role of dopamine in closing a perception-and-action-loop through linking mechanisms relevant for detection and production of social vocalizations. Moreover, our approach possibly provides a new means to study mania-like aberrant social interaction and communication in animal models for bipolar disorder.

  20. Determination of enantiomeric amphetamines as metabolites of illicit amphetamines and selegiline in urine by capillary electrophoresis using modified beta-cyclodextrin.

    Science.gov (United States)

    Heo, Y J; Whang, Y S; In, M K; Lee, K J

    2000-05-12

    The determination of enantiomeric amphetamine and methamphetamine in urine samples is important in order to distinguish use of the prescription drug selegiline (metabolized to R(-)-A and R(-)-MA) from the illicit use of S(+)-A and S(+)-MA. For the analysis of enantiomeric amphetamine (A) and methamphetamine (MA) in biological samples, the optimization of analytical condition was performed by capillary electrophoresis using chiral selectors including beta-cyclodextrin, carboxymethyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin. We have examined the factors to obtain the best chiral resolutions, separation efficiency and sensitivity, and wide concentration linearity. Optimum resolutions were achieved using 100 mM phosphate buffer, pH 2.5, containing 10 mM of carboxymethyl-beta-cyclodextrin. This method was applied for the quantitative determination of enantiomeric amphetamine and methamphetamine in urine samples obtained from patients taking illicit amphetamines or from rats and patients taking selegiline. Acceptable quantitative results in terms of resolution, precision, sensitivity and linearity were obtained from the real urine samples containing wide-ranging concentrations of A and MA by using two concentrations of internal standards, alpha(+)- (1 microg/ml) and beta-phenylethylamine (50 microg/ml).

  1. Amphetamines promote mitochondrial dysfunction and DNA damage in pulmonary hypertension

    Science.gov (United States)

    Chen, Pin-I; Cao, Aiqin; Miyagawa, Kazuya; Tojais, Nancy F.; Hennigs, Jan K.; Li, Caiyun G.; Sweeney, Nathaly M.; Inglis, Audrey S.; Wang, Lingli; Li, Dan; Ye, Matthew; Feldman, Brian J.

    2017-01-01

    Amphetamine (AMPH) or methamphetamine (METH) abuse can cause oxidative damage and is a risk factor for diseases including pulmonary arterial hypertension (PAH). Pulmonary artery endothelial cells (PAECs) from AMPH-associated-PAH patients show DNA damage as judged by γH2AX foci and DNA comet tails. We therefore hypothesized that AMPH induces DNA damage and vascular pathology by interfering with normal adaptation to an environmental perturbation causing oxidative stress. Consistent with this, we found that AMPH alone does not cause DNA damage in normoxic PAECs, but greatly amplifies DNA damage in hypoxic PAECs. The mechanism involves AMPH activation of protein phosphatase 2A, which potentiates inhibition of Akt. This increases sirtuin 1, causing deacetylation and degradation of HIF1α, thereby impairing its transcriptional activity, resulting in a reduction in pyruvate dehydrogenase kinase 1 and impaired cytochrome c oxidase 4 isoform switch. Mitochondrial oxidative phosphorylation is inappropriately enhanced and, as a result of impaired electron transport and mitochondrial ROS increase, caspase-3 is activated and DNA damage is induced. In mice given binge doses of METH followed by hypoxia, HIF1α is suppressed and pulmonary artery DNA damage foci are associated with worse pulmonary vascular remodeling. Thus, chronic AMPH/METH can induce DNA damage associated with vascular disease by subverting the adaptive responses to oxidative stress. PMID:28138562

  2. Quantum repeated games revisited

    CERN Document Server

    Frackiewicz, Piotr

    2011-01-01

    We present a scheme for playing quantum repeated 2x2 games based on the Marinatto and Weber's approach to quantum games. As a potential application, we study twice repeated Prisoner's Dilemma game. We show that results not available in classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games.

  3. Reinforcer magnitude affects delay discounting and influences effects of d-amphetamine in rats.

    Science.gov (United States)

    Krebs, Christopher A; Reilly, William J; Anderson, Karen G

    2016-09-01

    Impulsive choice in humans can be altered by changing reinforcer magnitude; however, this effect has not been found in rats. Current levels of impulsive choice can also influence effects of d-amphetamine. This study used a within-subject assessment to determine if impulsive choice is sensitive to changes in reinforcer magnitude, and whether effects of d-amphetamine are related to current levels of impulsive choice. A discounting procedure in which choice was for a smaller reinforcer available immediately or a larger reinforcer available after a delay that increased within session was used. Reinforcer magnitude was manipulated between conditions and impulsive choice was quantified using area under the curve (AUC). In the Smaller-Magnitude (SM) Condition, choice was between one food pellet and three food pellets. In the Larger-Magnitude (LM) Condition, choice was between two food pellets and six food pellets. Impulsive choice was greater in the SM Condition compared to the LM Condition. Further, effects of d-amphetamine (0.1-1.8mg/kg) were related to differences in impulsive choice. d-Amphetamine increased impulsive choice in the LM Condition, but had no effect on impulsive choice in the SM Condition. Overall, these results show that impulsive choice in rats is sensitive to changes in reinforcer magnitude, and that effects of d-amphetamine are influenced by current levels of impulsive choice.

  4. Determination of ketamine and amphetamines in hair by LC/MS/MS.

    Science.gov (United States)

    Tabernero, María Jesús; Felli, Maria Linda; Bermejo, Ana María; Chiarotti, Marcello

    2009-12-01

    A liquid chromatography-tandem mass spectrometry method was developed for the determination of ketamine (with its metabolite norketamine) and some amphetamines (amphetamine, methamphetamine, methylenedioxyamphetamine, and 3,4-methylenedioxymethamphetamine). This method was developed to determine these compounds in hair and is able to simultaneously quantify all of them in human hair. Hair samples (20 mg) were washed and pulverized, and an extraction with formic acid (0.01%) and ultrasonication for 4 h was used. Deuterated analogs of the analytes were used as internal standards for quantification. Linearity from 0.5 to 25 ng/mg was obtained for both ketamine (and norketamine) and amphetamines with correlation coefficients exceeding 0.99. The limit of detection and the limit of quantification obtained were 0.1 and 0.5 ng/mg, respectively, for ketamine and amphetamines. A total of 25 hair samples from known drug abusers (relating to designer drug consumption or consumption of amphetamines) were examined by this validated method. The results show that the proposed method is suitable for testing these drugs in a single sample of hair. In addition, it is simpler and faster than analysis by conventional methods such as gas chromatography-mass spectrometry, which usually require a more laborious extraction procedure and, in most of cases, an additional derivatization process.

  5. A rapid method for the extraction, enantiomeric separation and quantification of amphetamines in hair.

    Science.gov (United States)

    Strano-Rossi, Sabina; Botrè, Francesco; Bermejo, Ana Maria; Tabernero, Maria Jesús

    2009-12-15

    This paper presents a rapid and sensitive method for the determination and chiral separation of amphetamines and related designer drugs in hair samples. The substances are extracted from hair matrix by a 30 min treatment with a saturated carbonate buffer at pH 10 under ultrasonication. A commercial chiral derivatizing agent, trifluoroacetyl-prolyl chloride, is then added to the solution that is directly extracted with hexane and subsequently analyzed by GC/MS in SIM mode. R and S isomers of amphetamine, methamphetamine, MDA, MDMA and MDEA can be separated and detected with a limit of detection of 0.1 ng/mg for amphetamine, methamphetamine and MDA, and of 0.2 ng/mg for MDMA and MDEA. The method was then applied to 12 samples from suspected amphetamines abusers, showing the presence of both isomers of amphetamine and MDMA in one sample (27 and 1.5 ng/mg, respectively) and of MDMA in further eight samples, in concentrations ranging from traces to 2.7 ng/mg. No differences were observed in the disposition of different isomers in hair.

  6. The risky cocktail: what combination effects can we expect between ecstasy and other amphetamines?

    Science.gov (United States)

    Dias da Silva, Diana; Carmo, Helena; Silva, Elisabete

    2013-01-01

    The recreational and illicit use of amphetaminic designer compounds, specially 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), is of concern worldwide. Such psychostimulating drugs are frequently present as complex mixtures in 'rave' pills, making concomitant polysubstance use a common trend. However, the understanding of possible combination effects with these substances is still scarce. The present study was aimed at predicting the cytotoxic effects of mixtures of four amphetaminic derivatives: MDMA, methamphetamine, 4-methylthioamphetamine and d-amphetamine in a human hepatoma cell line. Concentration-response curves for all single-mixture components were recorded by the MTT assay. Data obtained for individual agents were then used to compute the additivity expectations for mixtures of definite composition, using the pharmacological models of concentration addition (CA) and independent action. By comparing the predicted calculations with the experimentally observed effects, we concluded that CA accurately predicts the combination of amphetamines, which act together to generate additive effects over a large range of concentrations. Notably, we observed substantial mixture effects even when each drug was present at low concentrations, which individually produced unnoticeable effects. Nonetheless, for all tested mixtures, a small deviation from additivity was observed towards higher concentrations, particularly at high effect levels. A possible metabolic interaction, which could explain such deviation, was investigated, and it was observed that at higher mixture concentrations increased MDMA metabolism could be contributing to divergences from additivity. In conclusion, the present work clearly demonstrates that potentially harmful interactions among amphetaminic drugs are expected when these drugs are taken concomitantly.

  7. Frontline immunochromatographic device for on-site urine testing of amphetamines: laboratory validation using authentic specimens.

    Science.gov (United States)

    Beck, O; Kraft, M; Moeller, M R; Smith, B L; Schneider, S; Wennig, R

    2000-03-01

    We evaluated a new test device for amphetamines and methamphetamines (Frontline, cut-off limit 300 ng/mL) using authentic clinical and forensic specimens. The device is based on immunochromatography and is dipped into urine and read visually by comparison with a colour scale after a few minutes. A total of 658 specimens were tested by comparing results of the screening procedure with established immunoassays. Discordant results were further investigated by gas chromatography mass spectrometry or gas chromatography (with flame ionization detector). The Frontline device had a sensitivity of 93% and a specificity of 98%. When specimens were classified by urine amphetamine concentration, close agreement was obtained at concentrations below 150 ng/mL and above 1000 ng/mL. A small number of specimens with amphetamine concentrations between 300 and 1000 ng/mL tested negative in the Frontline test. This finding could to some extent be explained by the enantioselectivity of the antibodies in the Frontline test to d-amphetamine. We conclude that the performance of the Frontline test device for amphetamines is adequate for presumptive clinical and forensic screening.

  8. Determination of amphetamines in human urine by headspace solid-phase microextraction and gas chromatography.

    Science.gov (United States)

    Raikos, Nikolaos; Christopoulou, Klio; Theodoridis, Georgios; Tsoukali, Heleni; Psaroulis, Dimitrios

    2003-06-05

    Solid-phase microextraction (SPME) is under investigation for its usefulness in the determination of a widening variety of volatile and semivolatile analytes in biological fluids and materials. Semivolatiles are increasingly under study as analytical targets, and difficulties with small partition coefficients and long equilibration times have been identified. Amphetamines were selected as semivolatiles exhibiting these limitations and methods to optimize their determination were investigated. A 100- micro m polydimethylsiloxane (PDMS)-coated SPME fiber was used for the extraction of the amphetamines from human urine. Amphetamine determination was made using gas chromatography (GC) with flame-ionization detection (FID). Temperature, time and salt saturation were optimized to obtain consistent extraction. A simple procedure for the analysis of amphetamine (AMP) and methamphetamine (MA) in urine was developed and another for 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methamphetamine (MDMA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA) using headspace solid-phase microextraction (HS-SPME) and GC-FID. Higher recoveries were obtained for amphetamine (19.5-47%) and methamphetamine (20-38.1%) than MDA (5.1-6.6%), MDMA (7-9.6%) and MDEA (5.4-9.6%).

  9. delta(13)C and delta(2)H isotope ratios in amphetamine synthesized from benzaldehyde and nitroethane.

    Science.gov (United States)

    Collins, Michael; Salouros, Helen; Cawley, Adam T; Robertson, James; Heagney, Aaron C; Arenas-Queralt, Andrea

    2010-06-15

    Previous work in these laboratories and by Butzenlechner et al. and Culp et al. has demonstrated that the delta(2)H isotope value of industrial benzaldehyde produced by the catalytic oxidation of toluene is profoundly positive, usually in the range +300 per thousand to +500 per thousand. Synthetic routes leading to amphetamine, methylamphetamine or their precursors and commencing with such benzaldehyde may be expected to exhibit unusually positive delta(2)H values. Results are presented for delta(13)C and delta(2)H isotope values of 1-phenyl-2-nitropropene synthesized from an industrial source of benzaldehyde, having a positive delta(2)H isotope value, by a Knoevenagel condensation with nitroethane. Results are also presented for delta(13)C and delta(2)H isotope values for amphetamine prepared from the resulting 1-phenyl-2-nitropropene. The values obtained were compared with delta(13)C and delta(2)H isotope values obtained for an amphetamine sample prepared using a synthetic route that did not involve benzaldehyde. Finally, results are presented for samples of benzaldehyde, 1-phenyl-2-nitropropene and amphetamine that had been seized at a clandestine amphetamine laboratory.

  10. Oral fluid with three modes of collection and plasma methamphetamine and amphetamine enantiomer concentrations after controlled intranasal l-methamphetamine administration.

    Science.gov (United States)

    Newmeyer, Matthew N; Concheiro, Marta; da Costa, Jose Luiz; Flegel, Ronald; Gorelick, David A; Huestis, Marilyn A

    2015-10-01

    Methamphetamine is included in drug testing programmes due to its high abuse potential. d-Methamphetamine is a scheduled potent central nervous system stimulant, while l-methamphetamine is the unscheduled active ingredient in the over-the-counter nasal decongestant Vicks® VapoInhaler™. No data are available in oral fluid (OF) and few in plasma after controlled Vicks® VapoInhaler™ administration. We quantified methamphetamine and amphetamine enantiomers in OF collected with two different devices and plasma via a fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Additionally, OF were analyzed with an on-site screening device. Sixteen participants received 7 Vicks® VapoInhaler™ doses according to manufacturer's recommendations. Specimens were collected before and up to 32 h after the first dose. No d-methamphetamine or d-amphetamine was detected in any sample. All participants had measurable OF l-methamphetamine with median maximum concentrations 14.8 and 16.1 μg/L in Quantisal™ and Oral-Eze® devices, respectively, after a median of 5 doses. One participant had measurable OF l-amphetamine with maximum concentrations 3.7 and 5.5 μg/L after 6 doses with the Quantisal™ and Oral-Eze® devices, respectively. There were no positive DrugTest® 5000 results. In the cutoff range 20-50 μg/L methamphetamine with amphetamine ≥limit of detection, 3.1-10.1% of specimens were positive; first positive results were observed after 1-4 doses. Two participants had detectable plasma l-methamphetamine, with maximum observed concentrations 6.3 and 10.0 μg/L after 2 and 5 doses, respectively. Positive OF and plasma methamphetamine results are possible after Vicks® VapoInhaler™ administration. Chiral confirmatory analyses are necessary to rule out VapoInhaler™ intake. Implementing a selective d-methamphetamine screening assay can help eliminate false-positive OF results.

  11. Neurotoxicity of β-Keto Amphetamines: Deathly Mechanisms Elicited by Methylone and MDPV in Human Dopaminergic SH-SY5Y Cells.

    Science.gov (United States)

    Valente, Maria João; Bastos, Maria de Lourdes; Fernandes, Eduarda; Carvalho, Félix; Guedes de Pinho, Paula; Carvalho, Márcia

    2017-04-19

    Synthetic cathinones (β-keto amphetamines) act as potent CNS stimulants similarly to classical amphetamines, which raise concerns about their potential neurotoxic effects. The present in vitro study aimed to explore and compare the mechanisms underlying the neurotoxicity of two commonly abused cathinone derivatives, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV), with those of 3,4-methylenedioxymethamphetamine (MDMA), using undifferentiated and differentiated SH-SY5Y cells. Following a 24 h exposure period, methylone and MDPV induced loss of cell viability in a concentration-dependent manner, in the following order of potency: MDPV ≈ MDMA > methylone. Dopaminergic differentiated cells evidenced higher sensitivity to the neurotoxic effects of both cathinones and MDMA than the undifferentiated ones, but this effect was not inhibited by the DAT inhibitor GBR 12909. Intracellular oxidative stress mediated by methylone and MDPV was demonstrated by the increase in reactive oxygen and nitrogen species (ROS and RNS) production, depletion of intracellular reduced glutathione and increased oxidized glutathione levels. All three drugs elicited mitochondrial impairment, characterized by the mitochondrial membrane potential (Δψm) dissipation and intracellular ATP depletion. Apoptosis was found to be a common mechanism of cell death induced by methylone and MDPV, with evident chromatin condensation and formation of pyknotic nuclei, and activation of caspases 3, 8, and 9. In conclusion, the present data shows that oxidative stress and mitochondrial dysfunction play a role in cathinones-induced neuronal damage, ultimately leading to cell death by apoptosis.

  12. 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

    inhibit (-)-apomorphine-induced behaviours in non-human primates at doses that do not cause EPS. When (-)-OSU6162 was tested against d-amphetamine-induced behaviours a separation between dose levels that inhibit d-amphetamine effects and cause EPS was not observed. The data further substantiate a role...... for low affinity DA D2 antagonists in the pharmacological treatment of psychosis....

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  14. A case story, involving the use of maltitol, a sugar alcohol, as a cutting agent in amphetamine and cocaine powders

    DEFF Research Database (Denmark)

    Reitzel, Lotte Ask; Holm, Niels Bjerre; Linnet, Kristian

    2016-01-01

    In a criminal case involving cutting and resale of amphetamine and cocaine in the Copenhagen area of Denmark, maltitol was used as a cutting agent. The analysis of maltitol in seizures of pure diluents as well as in amphetamine and cocaine powders was carried out using reversed-phase high perform...

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

    Science.gov (United States)

    Hafizi, Hamid; Najafi Chermahini, Alireza; Mohammadnezhad, Gholamhossein; Teimouri, Abbas

    2015-02-01

    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.

  16. Amphetamine-related drugs neurotoxicity in humans and in experimental animals: Main mechanisms.

    Science.gov (United States)

    Moratalla, Rosario; Khairnar, Amit; Simola, Nicola; Granado, Noelia; García-Montes, Jose Ruben; Porceddu, Pier Francesca; Tizabi, Yousef; Costa, Giulia; Morelli, Micaela

    2017-08-01

    Amphetamine-related drugs, such as 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH), are popular recreational psychostimulants. Several preclinical studies have demonstrated that, besides having the potential for abuse, amphetamine-related drugs may also elicit neurotoxic and neuroinflammatory effects. The neurotoxic potentials of MDMA and METH to dopaminergic and serotonergic neurons have been clearly demonstrated in both rodents and non-human primates. This review summarizes the species-specific cellular and molecular mechanisms involved in MDMA and METH-mediated neurotoxic and neuroinflammatory effects, along with the most important behavioral changes elicited by these substances in experimental animals and humans. Emphasis is placed on the neuropsychological and neurological consequences associated with the neuronal damage. Moreover, we point out the gap in our knowledge and the need for developing appropriate therapeutic strategies to manage the neurological problems associated with amphetamine-related drug abuse. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Application of solid-phase microextraction combined with derivatization to the enantiomeric determination of amphetamines.

    Science.gov (United States)

    Cháfer-Pericás, C; Campíns-Falcó, P; Herráez-Hernández, R

    2006-03-18

    The utility of combining chiral derivatization and solid-phase microextraction (SPME) for the enantiomeric analysis of primary amphetamines by liquid chromatography has been investigated. Different derivatization/extraction strategies have been evaluated and compared using the chiral reagent o-phthaldialdehyde (OPA)-N-acetyl-l-cysteine (NAC) and fibres with a Carbowax-templated resin coating. Amphetamine, norephedrine and 3,4-methylenedioxyamphetamine (MDA) were used as model compounds. On the basis of the results obtained, a new method is presented based on the derivatization of the analytes in solution followed by SPME of the OPA-NAC derivatives formed. The proposed conditions have been applied to determine the compounds of interest at low ppm levels (urine samples. Data on the linearity, reproducibility, sensitivity and selectivity are given. The utility of the described procedure for the quantification of amphetamine, norephedrine and MDA enantiomers in different kind of samples is also discussed.

  18. 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.

  19. [Death after the intake of amphetamine/ecstasy: two case reports].

    Science.gov (United States)

    Wöllner, Kirsten; Stockhausen, Sarah; Mußhoff, Frank; Madea, Burkhard

    2015-01-01

    Synthetic amphetamines such as 3,4-methylenedioxy-N-methylamphetamine (MDMA, Ecstasy) have become recreational drugs in German discotheques because of their euphoric and mood-brightening effects. However, their consumption involves considerable risks, which may even be lethal under certain circumstances. A 19-year-old man was taken to a university hospital for suspected intoxication with a narcotic drug, where he died the next day. As cause of death "fulminant liver failure" was diagnosed. In blood from the femoral vein, MDMA was found in a concentration of 4.27 mg/l. Histological examination showed acute necrosis of the liver and parenchymatous bleeding. The second case is that of a 39-year-old man who collapsed at his workplace and died in hospital shortly afterwards. In his rucksack, a small bag with 1.6 g of amphetamine was found. Analysis of blood from the femoral vein showed an amphetamine concentration of 1.08 mg/l.

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

    Science.gov (United States)

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

    2013-01-01

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

  1. Repeated Witnessing of Conspecifics in Pain : Effects on Emotional Contagion

    NARCIS (Netherlands)

    Carrillo, Maria; Migliorati, Filippo; Bruls, Rune; Han, Yingying; Heinemans, Mirjam; Pruis, Ilanah; Gazzola, V.; Keysers, C.

    2015-01-01

    Witnessing of conspecifics in pain has been shown to elicit socially triggered freezing in rodents. It is unknown how robust this response is to repeated exposure to a cage-mate experiencing painful stimulation. To address this question, shock-experienced Observer rats repeatedly witnessed familiar

  2. Determination of amphetamines in hair by GC/MS after small-volume liquid extraction and microwave derivatization.

    Science.gov (United States)

    Meng, Pinjia; Zhu, Dan; He, Hongyuan; Wang, Yanyan; Guo, Fei; Zhang, Liang

    2009-09-01

    We report here on the results of a procedure for the determination of amphetamine drugs in hair. The procedure is simple and sensitive. The results from the procedure using small-volume extraction matches perfectly with those either from using the derivatization method or selected ion monitoring (SIM) detection. We validated our method using four different amine drugs, including amphetamine, methamphetamine, methylenedioxy-amphetamine and methylenedioxy-methamphetamine. The detection limit for these drugs is about 50 +/- 7.5 pg/mg in hair and the intra-day and inter-day reproducibility are within 15% at most drug concentrations. Moreover, we also showed the utility of the procedure in analyses of authentic hair samples taken from amphetamine abusers, and demonstrated that the method meets the requirement for the analysis of a trace amounts of amphetamines in human hair.

  3. Differential effects of amphetamines-induced neurotoxicity on appetitive and aversive Pavlovian conditioning in mice.

    Science.gov (United States)

    Achat-Mendes, Cindy; Ali, Syed F; Itzhak, Yossef

    2005-06-01

    The abuse of substituted amphetamines such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy) can result in neurotoxicity, manifested as the depletion of dopamine (DA) and 5-hydroxytriptamine (5-HT; serotonin) axon terminal markers in humans and animal models. Human METH and MDMA users exhibit impairments in memory and executive functions, which may be a direct consequence of the neurotoxic potential of amphetamines. The objective of this study was to investigate the influence of amphetamines-induced neurotoxicity on Pavlovian learning. Using mouse models of selective DA neurotoxicity (METH; 5 mg/kg x 3), selective 5-HT neurotoxicity (fenfluramine /FEN; 25 mg/kg x 4) and dual DA and 5-HT neurotoxicity (MDMA; 15 mg/kg x 4), appetitive and aversive conditioning were investigated. Dopaminergic neurotoxicity significantly impaired METH and cocaine conditioned place preference (CPP), but had no effect on LiCl-induced conditioned place aversion (CPA). In contrast, serotonergic neurotoxicity significantly enhanced CPP, and had no effect on CPA. Dual dopaminergic/serotonergic neurotoxicity had no apparent effect on CPP; however, CPA was significantly attenuated. Postmortem analysis revealed that significantly diminished levels of DA and 5-HT markers persisted in the striatum, frontal cortex, hippocampus, and amygdala. These findings suggest that amphetamines-induced dopaminergic and serotonergic neurotoxicity exert opposing influences on the affective state produced by subsequent drug reward, while dual dopaminergic/serotonergic neurotoxicity impairs associative learning of aversive conditioning. Furthermore, results revealed that amphetamines-induced DA and 5-HT neurotoxicity modulates appetitive Pavlovian conditioning similar to other DA and 5-HT neurotoxins. Modulation of Pavlovian conditioning by amphetamines-induced neurotoxicity may be relevant to compulsive drug-seeking behavior in METH and MDMA abusers.

  4. Methamphetamine and amphetamine isomer concentrations in human urine following controlled Vicks VapoInhaler administration.

    Science.gov (United States)

    Smith, Michael L; Nichols, Daniel C; Underwood, Paula; Fuller, Zachary; Moser, Matthew A; Flegel, Ron; Gorelick, David A; Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

    2014-10-01

    Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography-mass spectrometry (GC-MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended doses. To evaluate these hypotheses, 22 healthy adults were each administered one dose (two inhalations in each nostril) of a Vicks VapoInhaler every 2 h for 10 h on Day 1 (six doses), followed by a single dose on Day 2. Every urine specimen was collected as an individual void for 32 h after the first dose and assayed for d- and l-amphetamines specific isomers with a GC-MS method with >99% purity of R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl derivatives and 10 µg/L lower limits of quantification. No d-methamphetamine or d-amphetamine was detected in any urine specimen by GC-MS. The median l-methamphetamine maximum concentration was 62.8 µg/L (range: 11.0-1,440). Only two subjects had detectable l-amphetamine, with maximum concentrations coinciding with l-methamphetamine peak levels, and always ≤ 4% of the parent's maximum. Three commercial immunoassays for amphetamines EMIT(®) II Plus, KIMS(®) II and DRI(®) had sensitivities, specificities and efficiencies of 100, 97.8, 97.8; 100, 99.6, 99.6 and 100, 100, 100%, respectively. The immunoassays had high efficiencies, but our first hypothesis was not affirmed. The EMIT(®) II Plus assay produced 2.2% false-positive results, requiring an enantiomer-specific confirmation.

  5. 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

  6. Sewer epidemiology mass balances for assessing the illicit use of methamphetamine, amphetamine and tetrahydrocannabinol.

    Science.gov (United States)

    Khan, Usman; Nicell, Jim A

    2012-04-01

    In sewer epidemiology, mass balances are used to back-extrapolate measurements of wastewater influent concentrations of appropriate drug residues to assess the parent illicit drug's level of use in upstream populations. This study focussed on developing and refining mass balances for the use of illicit methamphetamine, amphetamine and tetrahydrocannabinol. As a first step, a multi-criteria evaluation was used to select unchanged methamphetamine, unchanged amphetamine and 11-nor-9-carboxy-tetrahydrocannabinol as the most appropriate drug residues to track a selected population's use of illicit methamphetamine, amphetamine and tetrahydrocannabinol, respectively. For each of these selected drug residues, mass balances were developed by utilizing all disposition data available for their release from all their respective sources, incorporating route-of-administration considerations where relevant, and accounting for variations in the metabolic capacity of users of the various relevant licit and illicit sources. Further, since the selected drug residues for the use of methamphetamine and amphetamine cannot only result from their use but numerous other licit and illicit sources, comprehensive general source models were developed for their enantiomeric-specific release to sewers. The relative importance of the sources identified in the general source model was evaluated by performing national substance flow analyses for a number of countries. Results suggested that licit sources of methamphetamine are expected to be only of significance in populations where its illicit use is minor. Similarly, in populations where the use of illicitly produced amphetamine is currently of relevance, licit contributions to the sewer loads of amphetamine are likely to be of negligible importance. Lastly, the study of tetrahydrocannabinol back-extrapolation mass balances suggested that further research is required to assess the importance of fecal elimination of 11-nor-9-carboxy

  7. 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.

  8. Combination effects of amphetamines under hyperthermia - the role played by oxidative stress.

    Science.gov (United States)

    da Silva, Diana Dias; Silva, Elisabete; Carmo, Helena

    2014-06-01

    Rise in body temperature is a life-threatening consequence of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) abuse. We evaluated the impact of hyperthermia on the cytotoxicity of combinations of MDMA and three other amphetamines, often co-ingested. For this, Hep G2 cells were exposed to MDMA, d-amphetamine, methamphetamine and 4-methylthioamphetamine, individually or combined, at 40.5 °C. The results were compared with normothermia data (37.0 °C). Mixture additivity expectations were calculated by independent action and concentration addition (CA) models. To delineate the mechanism(s) underlying the elicited effects, a range of stress endpoints was evaluated, including quantification of reactive oxygen/nitrogen species (ROS/RNS), lipid peroxidation, reduced/oxidized glutathione (GSH/GSSG), ATP and mitochondrial membrane potential (Δψm) changes. Our data show that, in hyperthermia, amphetamines acted additively and mixture effects were accurately predicted by CA. At 40.5 °C, even slight increases in the concentrations of each drug/mixture promoted significant rises in cytotoxicity, which quickly shifted from roughly undetectable to maximal mortality. Additionally, the increase of RNS/ROS production, decrease of GSH, ATP depletion and mitochondrial impairment were exacerbated under hyperthermia. Importantly, when equieffective cytotoxic concentrations of the mixture and individual amphetamines were compared for all tested stress endpoints, mixture effects did not deviate from those elicited by individual treatments, suggesting that these amphetamines have a similar mode of action, which is not altered in combination. Concluding, our data indicate that amphetamine mixtures produce deleterious effects, even when individual drugs are combined at negligible concentrations. These effects are strongly exacerbated in hyperthermia, emphasizing the potential increased risks of ecstasy intake, especially when hyperthermia occurs concurrently with polydrug abuse.

  9. Amphetamine administration improves neurochemical outcome of lateral fluid percussion brain injury in the rat.

    Science.gov (United States)

    Dhillon, H S; Dose, J M; Prasad, R M

    1998-09-07

    This study examined the effects of the administration of D-amphetamine on the regional accumulation of lactate and free fatty acids (FFAs) after lateral fluid percussion (FP) brain injury in the rat. Rats were subjected to either FP brain injury of moderate severity (1.9 to 2.0 atm) or sham operation. At 5 min after injury, rats were treated with either d-amphetamine (4 mg/kg, i.p.) or saline. At 30 min and 60 min after brain injury, brains were frozen in situ, and cortices and hippocampi were excised at 0 degrees C. In the saline-treated brain injured rats, levels of lactate were increased in the ipsilateral left cortex and hippocampus at 30 min and 60 min after injury. These increases were attenuated by the administration of D-amphetamine at 5 min after lateral FP brain injury. At 30 and 60 min after FP brain injury, increases in the levels of all individual FFAs (palmitic, stearic, oleic and arachidonic acids) and of total FFAs were also observed in the ipsilateral cortex of the saline-treated injured rats. These increases in the ipsilateral cortex and hippocampus were also attenuated by the administration of d-amphetamine. Neither levels of lactate nor levels of FFAs were increased in the contralateral cortex in the saline-treated injured rats at 30 min or 60 min after FP brain injury. The levels of lactate and FFAs in the contralateral cortex were also unaffected by the administration of D-amphetamine. These results suggest that the attenuation of increases in the levels of lactate and FFAs in the ipsilateral cortex and hippocampus may be involved in the amphetamine-induced improvement in behavioral outcome after lateral FP brain injury.

  10. Sulfur compounds in therapy: Radiation-protective agents, amphetamines, and mucopolysaccharide sulfation

    Energy Technology Data Exchange (ETDEWEB)

    Foye, W.O. (Massachusetts College of Pharmacy and Allied Health Sciences, Boston (United States))

    1992-09-01

    Sulfur-containing compounds have been used in the search for whole-body radiation-protective compounds, in the design of amphetamine derivatives that retain appetite-suppressive effects but lack most behavioral effects characteristic of amphetamines, and in the search for the cause of kidney stone formation in recurrently stoneforming patients. Organic synthetic procedures were used to prepare radiation-protective compounds having a variety of sulfur-containing functional groups, and to prepare amphetamine derivatives having electron-attracting sulfur functions. In the case of the kidney stone causation research, isolation of urinary mucopolysaccharides (MPS) from recurrently stoneforming patients was carried out and the extent of sulfation of the MPS was determined by electrophoresis. Whole-body radiation-protective agents with a high degree of protection against lethal doses of gamma-radiation in mice were found in a series of quinolinium and pyridinium bis(methylthio) and methylthio amino derivatives. Mechanism studies showed that the copper complexes of these agents mimicked the beneficial action of superoxide dismutase. Electron-attracting sulfur-containing functions on amphetamine nitrogen, as well as 4'-amino nitrogen provided amphetamine derivatives with good appetite-suppressant effects and few or no adverse behavioral effects. Higher than normal levels of sulfation of the urinary MPS of stone formers suggested a cause for recurrent kidney stone formation. A sulfation inhibitor was found to prevent recurrence of stone formation and inhibit growth of existing stones. The inclusion of various sulfur-containing functions in organic molecules yielded compounds having whole-body radiation protection from lethal doses of gamma-radiation in animals. The presence of electron-attracting sulfur functions in amphetamine gave derivatives that retained appetite-suppressant effects and eliminated most adverse behavioral effects.

  11. 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.

  12. The Impact of Illicit Use of Amphetamine on Male Sexual Functions.

    Science.gov (United States)

    Chou, Nan-Hua; Huang, Yung-Jui; Jiann, Bang-Ping

    2015-08-01

    Data concerning the impact of amphetamine on male sexual functions are limited, although amphetamine has been used as an aphrodisiac. This cross-sectional study was to assess the impact of illicit use of amphetamine on male sexual functions. Male illicit drug users in a Drug Abstention and Treatment Center were recruited to complete a self-administered questionnaire, and data were compared with age-matched controls. The International Index of Erectile Function (IIEF) and global assessment questions were used to assess sexual functions. Of 1,159 amphetamine mono-illicit drug users, the mean age was 31.9 ± 7.5 (18-57) years, and mean duration of drug use was 30.7 ± 52.2 (median 9, range 0.1-252) months. Half of them reported that drug use had no impact on their sexual functions. The other half reported drug impacts as reduced erectile rigidity and sexual life satisfaction, enhanced orgasmic intensity, and prolonged ejaculation latency time more often than the opposite effects, while they reported enhanced or reduced effect equally on sexual desire. Dosing frequency of amphetamine was associated with its impact on sexual functions, but duration of its use had little association with that. Compared with 211 age-matched controls, the amphetamine mono-illicit drug users had lower IIEF scores in the domains of erectile function, orgasmic function, and overall satisfaction, but there are no significant differences in intercourse satisfaction and sexual desire scores. The prevalence of erectile dysfunction (ED) was significantly higher in the drug users than in the controls (29.3% vs. 11.9%). The odds ratio of ED for amphetamine use was 2.1 (95% confidence interval 1.2-3.6) after adjustment for other risk factors. The impact of illicit use of amphetamine on male sexual functions varied among users, and their ED prevalence was higher than the controls. © 2015 International Society for Sexual Medicine.

  13. 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

    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...... and, in spite of only the 0.5mg/kg dose proved statistically significant, the results indicate this to be dose-related. We have demonstrated the phenomenon of PPI of the startle reflex in landrace pigs and its disruption by d-amphetamine. Studies of sensorimotor gating defects could be a valuable...

  14. Selectivity manipulation using nonaqueous capillary electrophoresis. Application to tropane alkaloids and amphetamine derivatives.

    Science.gov (United States)

    Cherkaoui, S; Varesio, E; Christen, P; Veuthey, J L

    1998-11-01

    Non-aqueous capillary electrophoresis was investigated for its potential in the analysis of pharmaceutical compounds, namely tropane alkaloids and amphetamine derivatives. The separation of these drugs was compared in aqueous and organic media such as methanol and/or acetonitrile. Selectivity, migration times and efficiency were critically affected by the composition of the methanol/acetonitrile mixture, as well as by the nature and the concentration of the electrolyte. In particular, the migration orders of two positional isomers, littorine and hyoscyamine, were inverted in the presence of trifluoroacetic acid in the nonaqueous medium. The same behavior was observed for amphetamine-methamphetamine and for two methylenedioxyamphetamine derivatives.

  15. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  16. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  17. Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants.

    Science.gov (United States)

    Weyandt, Lisa L; Oster, Danielle R; Marraccini, Marisa E; Gudmundsdottir, Bergljot Gyda; Munro, Bailey A; Zavras, Brynheld Martinez; Kuhar, Ben

    2014-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity that cause functional impairment. Recent research indicates that symptoms persist into adulthood in the majority of cases, with prevalence estimates of approximately 5% in the school age population and 2.5%-4% in the adult population. Although students with ADHD are at greater risk for academic underachievement and psychosocial problems, increasing numbers of students with ADHD are graduating from high school and pursuing higher education. Stimulant medications are considered the first line of pharmacotherapy for individuals with ADHD, including college students. Although preliminary evidence indicates that prescription stimulants are safe and effective for college students with ADHD when used as prescribed, very few controlled studies have been conducted concerning the efficacy of prescription stimulants with college students. In addition, misuse of prescription stimulants has become a serious problem on college campuses across the US and has been recently documented in other countries as well. The purpose of the present systematic review was to investigate the efficacy of prescription stimulants for adolescents and young adults with ADHD and the nonmedical use and misuse of prescription stimulants. Results revealed that both prostimulant and stimulant medications, including lisdexamfetamine dimesylate, methylphenidate, amphetamines, and mixed-amphetamine salts, are effective at reducing ADHD symptoms in adolescents and adults with ADHD. Findings also suggest that individuals with ADHD may have higher rates of stimulant misuse than individuals without the disorder, and characteristics such as sex, race, use of illicit drugs, and academic performance are associated with misuse of stimulant medications. Results also indicate that individuals both with and without ADHD are more likely to misuse short-acting agents

  18. Amphetamines as potential inducers of fatalities: a review in the district of Ghent from 1976-2004.

    Science.gov (United States)

    De Letter, Els A; Piette, Michel H A; Lambert, Willy E; Cordonnier, Jan A C M

    2006-01-01

    Abuse of amphetamine (AMP) and its derivatives, such as 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), 3,4-methylenedioxyethylamphetamine (MDEA, MDE), and 3,4-methylenedioxyamphetamine (MDA) is an important public issue. Fatalities following ingestion of these substances are not infrequent in current forensic practice. The aim of this study was twofold. Firstly, considering the wide range of blood levels reported in fatalities, to provide insight into the interpretation of a quantified blood level and, secondly, to examine and discuss possible causes, mechanisms and manners of death. All the medico-legal files between January 1976 and December 2004 were skimmed through to investigate whether amphetamine and/or derivatives were involved in the fatal outcome. Particularly, in addition to overdose cases due to or including amphetamines, all amphetamines-related fatalities were examined. In addition to AMP, MDMA, MDEA, and MDA, two other amphetamine derivatives, namely 4-methylthioamphetamine (4-MTA) and para-methoxyamphetamine (PMA) were considered. In 34 fatalities, amphetamines were involved and the majority were men, under the age of 25 years. A wide range of blood levels was found: e.g. MDMA blood concentrations in cases of 'pure' intoxication were found between 0.27 and 13.51 microg/ml. The age and sex distribution as well as the broad range of quantified amphetamines blood levels were in line with those reported in the literature. In our study group, 'pure' intoxications with amphetamines, polydrug overdoses, and the combination of amphetamines use and polytrauma were the most prominent causes of death. Considering the manner of death in these fatalities, unintentional overdoses were most frequent, though suicides, traffic accidents, and criminal offences associated with amphetamines use also accounted for significant percentages. Acute to subacute cardiopulmonary failure was the most frequent mechanism of death, followed by (poly)trauma, mechanical

  19. Recursive quantum repeater networks

    CERN Document Server

    Van Meter, Rodney; Horsman, Clare

    2011-01-01

    Internet-scale quantum repeater networks will be heterogeneous in physical technology, repeater functionality, and management. The classical control necessary to use the network will therefore face similar issues as Internet data transmission. Many scalability and management problems that arose during the development of the Internet might have been solved in a more uniform fashion, improving flexibility and reducing redundant engineering effort. Quantum repeater network development is currently at the stage where we risk similar duplication when separate systems are combined. We propose a unifying framework that can be used with all existing repeater designs. We introduce the notion of a Quantum Recursive Network Architecture, developed from the emerging classical concept of 'recursive networks', extending recursive mechanisms from a focus on data forwarding to a more general distributed computing request framework. Recursion abstracts independent transit networks as single relay nodes, unifies software layer...

  20. Synthesis of polystyrene, poly(styrene/4-vinylpyridine), poly(p-nitrostyrene) and poly(p-aminostyrene)-coated silica and their extraction capabilities for amphetamine

    Energy Technology Data Exchange (ETDEWEB)

    Sun Changmei; Zhang Shuanhong [School of Chemistry and Materials Science, Ludong University, Yantai, Shandong 264025 (China); Qu Rongjun, E-mail: qurongjun@eyou.com [School of Chemistry and Materials Science, Ludong University, Yantai, Shandong 264025 (China); Sun Tao; Zhang Ying; Zhang Xiang; Song Jingyang [School of Chemistry and Materials Science, Ludong University, Yantai, Shandong 264025 (China)

    2010-11-01

    Several novel organic-inorganic hybrid materials, including polystyrene-coated silica (SG-PS), poly(styrene/4-vinylpyridine)-coated silica (SG-PVP), poly(p-nitrostyrene)-coated silica (SG-PS-NO{sub 2}) and poly(p-aminostyrene)-coated silica (SG-PS-NH{sub 2}), were synthesized in order to improve the extraction methods of harmful stimulants via solid phase extraction. The materials were characterized using infrared spectra (IR), scanning electron microscope (SEM), Brunauer-Emmett-Teller (BET) surface area measurement and thermogravimetric analysis (TG). The application of the new materials in solid phase extraction columns to extract methamphetamine revealed that the extraction capability of poly(styrene/4-vinylpyridine)-coated silica is the best among the four materials, which provides novel supporter materials for extracting amphetamine-derived drugs.

  1. Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants

    Directory of Open Access Journals (Sweden)

    Weyandt LL

    2014-09-01

    Full Text Available Lisa L Weyandt, Danielle R Oster, Marisa E Marraccini, Bergljot Gyda Gudmundsdottir, Bailey A Munro, Brynheld Martinez Zavras, Ben Kuhar Department of Psychology, University of Rhode Island, Kingston, RI, USA Abstract: Attention-deficit/hyperactivity disorder (ADHD is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity that cause functional impairment. Recent research indicates that symptoms persist into adulthood in the majority of cases, with prevalence estimates of approximately 5% in the school age population and 2.5%–4% in the adult population. Although students with ADHD are at greater risk for academic underachievement and psychosocial problems, increasing numbers of students with ADHD are graduating from high school and pursuing higher education. Stimulant medications are considered the first line of pharmacotherapy for individuals with ADHD, including college students. Although preliminary evidence indicates that prescription stimulants are safe and effective for college students with ADHD when used as prescribed, very few controlled studies have been conducted concerning the efficacy of prescription stimulants with college students. In addition, misuse of prescription stimulants has become a serious problem on college campuses across the US and has been recently documented in other countries as well. The purpose of the present systematic review was to investigate the efficacy of prescription stimulants for adolescents and young adults with ADHD and the nonmedical use and misuse of prescription stimulants. Results revealed that both prostimulant and stimulant medications, including lisdexamfetamine dimesylate, methylphenidate, amphetamines, and mixed-amphetamine salts, are effective at reducing ADHD symptoms in adolescents and adults with ADHD. Findings also suggest that individuals with ADHD may have higher rates of stimulant misuse than individuals without the disorder, and

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

    Science.gov (United States)

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

    2013-09-01

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

  3. Cloning and characterization of neuropeptide Y (NPY) and cocaine and amphetamine regulated transcript (CART) in Atlantic cod (Gadus morhua).

    Science.gov (United States)

    Kehoe, Amy S; Volkoff, Hélène

    2007-03-01

    Neuropeptide Y (NPY) and cocaine and amphetamine regulated transcript (CART) are two neuropeptides involved in the regulation of feeding in both mammals and fish. NPY stimulates feeding whereas CART inhibits feeding. In this study, we have cloned the full-length cDNA and complete genomic DNA sequences for NPY and CART in Atlantic cod. Atlantic cod preproNPY share a 45-85% identity with preproNPY from other fish whereas preproCART shows a 70% identity to CART peptides from zebrafish and goldfish. RT-PCR revealed that NPY mRNA is expressed in brain, in particular the forebrain, and in peripheral tissues, including intestine and kidney. CART mRNA is expressed throughout the brain and in ovaries. In order to assess the role of these peptides in the regulation of feeding, we examined changes in mRNA expression in the forebrain before, during and after a meal. NPY and CART mRNA both undergo peri-prandial changes in expression, with NPY levels being elevated around meal time and CART showing a decline 2 h after a meal. Food deprivation for 7 days induced a decrease in CART mRNA expression in the brain but did not affect NPY mRNA expression. Overall, our results suggest that NPY and CART are conserved peptides that might be involved in the regulation of feeding and other physiological functions in Atlantic cod.

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

    Science.gov (United States)

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

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

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

    Science.gov (United States)

    Brause, R.; Fricke, H.; Gerhards, M.; Weinkauf, R.; Kleinermanns, K.

    2006-08-01

    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-(H 2O) 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 S 0 → S 1 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-(H 2O) 1,2 are tentatively assigned.

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

    DEFF Research Database (Denmark)

    Binda, Francesca; Dipace, Concetta; Bowton, Erica

    2008-01-01

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

  7. Amphetamines in wastewater of the city Poznań (Poland)--estimation of drug abuse.

    Science.gov (United States)

    Nowicki, Piotr; Klos, Jolanta; Kokot, Zenon J

    2014-01-01

    The aim of the study was to determine the profile of amphetamines consumed by a community in Poland. Amphetamine, methamphetamine and MDMA (ecstasy) were detected in wastewater samples collected from the main Wastewater Treatment Plant in the city of Poznań (about 687 000 people) using liquid chromatography/tandem mass spectrometry (LC-MS-MS). Back-calculations used in the sewage epidemiology approach were applied to estimate the level of consumption of the drugs being analyzed. These types of studies were carried out for the first time in Poland for a considerable period--from June 2009 to December 2010. The analysis of variance (ANOVA) confirmed significant monthly differences in amphetamine consumption. The concentration of amphetamine, methamphetamine and MDMA in wastewater samples and the levels of their consumption were lower than reported in other European countries, but unexpectedly, the ratio of consumed methamphetamine to MDMA and the consumption level of methamphetamine were relatively high. This study shows that sewage epidemiology is a promising tool, especially when combined with classical methods, to estimate illicit drugs use in a particular population. Therefore, efforts should be made to monitor the profiles and consumption levels of drugs and to extend the scope of the research to other illicit substances, especially cannabinoids and cocaine.

  8. [Cardiogenic shock after ingestion of amphetamines on a ground of Mycoplasma myocarditis].

    Science.gov (United States)

    Berger, K; Hérault, M-C; Danel, V; Vincent, F; Jacquot, C

    2008-03-01

    Amphetamines are considered as narcotics in France. Their use induces modifications of the central nervous system and of the cardiovascular, respiratory and urinary systems by a sympathomimetic indirect effect. Here is reported the observation of a young woman who absorbed amphetamines causing a cardiogenic shock on a ground of acute myocarditis. The constitution of haemodynamic, respiratory and neurologic distresses lead to the endotracheal intubation of the patient. The haemodynamic status remaining shaky, despite the use of vasoactive drugs, a circulatory assistance by intra-aortic counter pulsation balloon was carried out. The initial echocardiography showed a left ventricular ejection fraction lower than 20%. Amphetamine's toxicity mechanisms still remain complicated; on cardiovascular plan, some cases of coronary artery spasm have been described. The coronarography, not accomplished immediately, was normal. Toxicological samples revealed an abnormally high amphetamines concentration. The severity of the cardiac attack was amplified by a Mycoplasma pneumoniae myocarditis. There was a positive evolution in eight days. Intoxication and infection can difficultly be dissociated in this case of cardiogenic shock.

  9. Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines.

    Science.gov (United States)

    McBride, Shawna M; Culver, Bruce; Flynn, Francis W

    2008-09-01

    This study examined critical periods in development to determine when offspring were most susceptible to dietary sodium manipulation leading to amphetamine sensitization. Wistar dams (n = 6-8/group) were fed chow containing low (0.12% NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal or early postnatal period (birth to 5 wk). Offspring were fed normal chow thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid intake, salt preference, response to amphetamine, open field behavior, plasma adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal gland weight were measured. BW was similar for all offspring. Offspring from the prenatal and postnatal HN group had increased BP, NaCl intake, and salt preference and decreased water intake relative to NN offspring. Prenatal HN offspring had greater BP than postnatal HN offspring. In response to amphetamine, both prenatal and postnatal LN and HN offspring had increased locomotor behavior compared with NN offspring. In a novel open field environment, locomotion was also increased in prenatal and postnatal LN and HN offspring compared with NN offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland weight measurement were greater in LN and HN offspring compared with NN offspring. These results indicate that early life experience with low- and high-sodium diets, during the prenatal or early postnatal period, is a stress that produces long-term changes in responsiveness to amphetamines and to subsequent stressors.

  10. Acceleration of cardiovascular-biological age by amphetamine exposure is a power function of chronological age

    Science.gov (United States)

    Norman, Amanda; Hulse, Gary Kenneth

    2017-01-01

    Background Amphetamine abuse is becoming more widespread internationally. The possibility that its many cardiovascular complications are associated with a prematurely aged cardiovascular system, and indeed biological organism systemically, has not been addressed. Methods Radial arterial pulse tonometry was performed using the SphygmoCor system (Sydney). 55 amphetamine exposed patients were compared with 107 tobacco smokers, 483 non-smokers and 68 methadone patients (total=713 patients) from 2006 to 2011. A cardiovascular-biological age (VA) was determined. Results The age of the patient groups was 30.03±0.51–40.45±1.15 years. This was controlled for with linear regression. The sex ratio was the same in all groups. 94% of amphetamine exposed patients had used amphetamine in the previous week. When the (log) VA was regressed against the chronological age (CA) and a substance-type group in both cross-sectional and longitudinal models, models quadratic in CA were superior to linear models (both pamphetamine exposure persisted after adjustment for all known cardiovascular risk factors (pamphetamines is associated with an advancement of cardiovascular-organismal age both over age and over time, and is robust to adjustment. That this is associated with power functions of age implies a feed-forward positively reinforcing exacerbation of the underlying ageing process. PMID:28243315

  11. Roche DAT immunoassay: sensitivity and specificity testing for amphetamines, cocaine, and opiates in oral fluid.

    Science.gov (United States)

    Crooks, C Richard; Brown, Sue

    2010-03-01

    Laboratory testing of oral fluid for drugs of abuse continues to expand in the workplace, legal, treatment, and health settings. In this study, we assessed recently developed homogeneous Roche DAT screening assays for amphetamines, cocaine metabolite [benzoylecgonine (BZE)], methamphetamines, and opiates in oral fluid. Precision and accuracy were assessed using control samples at +/-25% of cutoff. Sensitivity, specificity, and agreement compared to liquid chromatography-tandem mass spectrometry (LC-MS-MS) was assessed by analysis of oral fluid specimens collected from 994 subjects enrolled in a drug treatment or probation and parole drug-testing program. An additional 180 research specimens from Kroll Laboratories were analyzed for amphetamine and methamphetamine. Screening cutoff concentrations (ng/mL) were as follows: amphetamines, 40; cocaine metabolite, 3; methamphetamines, 40; and opiates, 10. LC-MS-MS analyses were performed with the following cutoff concentrations (ng/mL): amphetamine, 40; BZE, 2.0; methamphetamine, 40; and codeine or morphine, 10. The percent coefficient of variation ranged from 3.4% to 7.3%. Sensitivity and specificity of the Roche DAT assays compared to LC-MS-MS were > 94%, and agreement was > 96% for the four assays. The performance of the Roche DAT assays suggests these new homogeneous screening assays will be an attractive alternative to existing more labor-intensive enzyme immunoassays.

  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. Brain injury associated with widely abused amphetamines: neuroinflammation, neurogenesis and blood-brain barrier.

    Science.gov (United States)

    Silva, Ana P; Martins, Tânia; Baptista, Sofia; Gonçalves, Joana; Agasse, Fabienne; Malva, João O

    2010-12-01

    Over the course of the 20(th) century, it became increasingly clear that amphetamine-like psychostimulants carried serious abuse liability that has resulted in sociological use patterns that have been described as epidemics. In fact, drug addiction is a brain disease with a high worldwide prevalence, and is considered the most expensive of the neuropsychiatric disorders. This review goes beyond the previously well-documented evidence demonstrating that amphetamines cause neuronal injury. Cellular and molecular mechanisms involved in the neurotoxicity of psychostimulants drugs have been extensively described giving particular attention to the role of oxidative stress and metabolic compromise. Recently, it was shown that the amphetamine class of drugs of abuse triggers an inflammatory process, emerging as a critical concept to understand the toxic effects of these drugs. Moreover, it has been suggested that psychostimulants compromise the capacity of the brain to generate new neurons (neurogenesis), and can also lead to blood-brain barrier (BBB) dysfunction. Together, these effects may contribute to brain damage, allowing the entry of pathogens into the brain parenchyma and thus decreasing the endogenous brain repair resources. The overall objective of this review is to highlight experimental evidence in an attempt to clarify the role of neuroinflammation in amphetamines-induced brain dysfunction and the effect of these drugs on both neurogenesis and BBB integrity.

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

    Energy Technology Data Exchange (ETDEWEB)

    Brause, R. [Institut fuer Physikalische Chemie, Heinrich-Heine-Universitaet, Universitaetsstrasse 1, D-40225 Duesseldorf (Germany); Fricke, H. [Institut fuer Physikalische Chemie, Heinrich-Heine-Universitaet, Universitaetsstrasse 1, D-40225 Duesseldorf (Germany); Gerhards, M. [Institut fuer Physikalische Chemie, Heinrich-Heine-Universitaet, Universitaetsstrasse 1, D-40225 Duesseldorf (Germany); Weinkauf, R. [Institut fuer Physikalische Chemie, Heinrich-Heine-Universitaet, Universitaetsstrasse 1, D-40225 Duesseldorf (Germany); Kleinermanns, K. [Institut fuer Physikalische Chemie, Heinrich-Heine-Universitaet, Universitaetsstrasse 1, D-40225 Duesseldorf (Germany)], E-mail: kleinermanns@uni-duesseldorf.de

    2006-08-21

    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-(H{sub 2}O){sub 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 S{sub 0} {sup {yields}} S{sub 1} 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-(H{sub 2}O){sub 1,2} are tentatively assigned.

  15. 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).

  16. [The detection of amphetamines in urine samples using immunochromatographic test strips].

    Science.gov (United States)

    Shanin, I A; Khan, O Iu; Petukhov, A E; Smirnov, A V; Eremin, S A

    2012-01-01

    This study has demonstrated the possibility of using immunochromatographic test strips for the reliable qualitative detection of amphetamine and methamphetamine in the urine samples at a cut-off level of 300 ng/ml. The test strips obtained from different manufactures are shown to be slightly different in terms of specificity as appears from the frequency of cross-reactions with various pharmaceutical products and narcotic drugs. Also, the use of the immunochromatographic strips makes it possible to determine amphetamine in a range of concentrations from 100 to 1000 ng/ml by measuring the intensity of test-line colour with the help of a TotalLab TL120 programmer and special scanning programs. The analysis for amphetamine using the NrcoStop (Osiris S) immunochromatographic strips failed to confirm the presence of this substance in the urine samples from the subjects who had drunk 0.5 l of energy drinks, such as Adrenaline RUSH, Red Bull, and Burn. It means that the presence of amphetamine in the urine should not be attributed to the consumption of such drinks.

  17. [Application of solid-phase microextraction technique to the detection of amphetamines in urine by GC].

    Science.gov (United States)

    Liu, W; Shen, M

    1999-05-01

    A simple and rapid detection of nine amphetamines co-existing in urine was described. In the test, the method of solid-phase micro-extraction (SPME) by GC technique was used. Urine (1.0 ml), NaCl (0.3 g) and 4-phenylbutylamine (internal standard) were added into a vial (1.5 ml), then the sample was adjusted to pH 12 with 10% NaOH and sealed with a teflon-coated septum. After immersion of the SPME fiber (100 PDME) in the sample for 15 min, the SPME needle was inserted into the injection port of the GC and extruded for 3 min. The result showed that each peak from nine amphetamines compounds and internal standard was clearly separated. The calibration curves were linear from 0.2 to 15 micrograms/ml for most of five amphetamines with r between 0.9928-0.9995. The CV were less 10%. It is concluded that the method is simple, quick, accurate and useful for the practical detection of urine concentration of amphetamines.

  18. Performance of immunoassays in screening for opiates, cannabinoids and amphetamines in post-mortem blood.

    Science.gov (United States)

    Hino, Yukiko; Ojanperä, Ilkka; Rasanen, Ilpo; Vuori, Erkki

    2003-01-28

    Several immunoassay methods for screening of abused drugs in whole blood were evaluated in post-mortem forensic toxicology. Blood samples known to be positive or negative for opiates, cannabinoids or amphetamines by gas chromatography-mass spectrometry (GC-MS) were analysed by EMIT II Plus and EMIT d.a.u., Syva RapidTest and Triage 8 after acetone precipitation. In these experiments, the EMIT immunoassay method was modified by using the Dade Behring VIVA analyser to detect substances more sensitively. Low concentrations of abused drugs were detected in blood samples. The sensitivities of the modified EMIT method for opiates, cannabinoids and amphetamines were 100, 86 and 98%, respectively, whereas the values were below 86% with the other methods. The specificities of all immunoassay methods for opiates and cannabinoids were 83% or above but 51-85% for amphetamines. Sample rejection occurred in a few cases with the EMIT amphetamine assays. The modified EMIT immunoassay system presented here seems to be useful for screening of drugs of abuse in post-mortem blood samples, especially when urine is not available.

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

    Science.gov (United States)

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

    2009-01-01

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

  20. Effects of mescaline and amphetamine on simultaneous visual discrimination in two inbred strains of mice.

    Science.gov (United States)

    Castellano, C

    1979-03-29

    The effects of mescaline and amphetamine were investigated in BALB/cJ (BALB) and C57BL/6J (C57) mice using the five-choice Yerkes--Thompson Bryant--Bovet-Nitti apparatus for patterns discrimination. Two sets of experiments were carried out. In the first set, pretrial administration of mescaline (5, 10, and 20 mg/kg) was followed by performance improvements in the C57 mice, while performances of the BALB strain were impaired by the treatment, as compared with those of the saline-injected (4 ml/kg) controls. The pretrial administration of amphetamine (0.1, 0.25, and 0.5 mg/kg) improved performances of both strains. In a second set of experiments, the same effects as in the pretrial experiments were observed in both strains following administration of mescaline (20 mg/kg) and amphetamine (0.5 mg/kg) immediately after each experimental session. No effect was evident when the drugs were injected 2 h after training, suggesting that effects of the pretrial treatments were due to influences of mescaline and amphetamine on the consolidation processes of the two strains of mice tested.

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

    Energy Technology Data Exchange (ETDEWEB)

    Cody, J.T. (Air Force Drug Testing Laboratory, Brooks AFB, TX (USA))

    1990-01-01

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

  2. 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...

  3. 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...

  4. 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

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

    Science.gov (United States)

    Brunt, Tibor M; van Laar, Margriet; Niesink, Raymond J M; van den Brink, Wim

    2010-09-01

    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 cocaine throughout a period of 17 years (1992-2008). Both cocaine price and quality showed a decrease in The Netherlands during the studied period. We used time-series regression analysis to investigate whether price or quality of the drugs were associated with health care outcomes. Drug seizures were also added to the time-series regressions in order to check for possible effects of drug availability and supply. Price and quality of cocaine were strongly associated with health care outcomes of addiction treatment and hospital admissions. Price of amphetamine also showed a decrease during these 17 years, but was associated with an increase in addiction treatment only. Other amphetamine market variables did not show any relationship with the health care outcomes. It could be stated that following basic market logics does not apply equally to all psychostimulants of abuse. Other factors might play a role, such as the addictiveness or desirability of a specific drug in question. This finding is supportive of the dynamics of the illicit psychostimulant market affecting actual use and thereby health care outcomes. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  6. 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.

  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

    OpenAIRE

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Peltenburg, Hester, E-mail: H.Peltenburg@uu.nl [Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD Utrecht (Netherlands); Groothuis, Floris A.; Droge, Steven T.J. [Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD Utrecht (Netherlands); Bosman, Ingrid J. [Netherlands Forensic Institute, P.O. Box 24044, 2490 AA The Hague (Netherlands); Hermens, Joop L.M. [Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD Utrecht (Netherlands)

    2013-06-11

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

  9. β-Methylphenylethylamines: common fragmentation pathways with amphetamines in electrospray ionization collision-induced dissociation.

    Science.gov (United States)

    Brown, David H; Hansson, Robert; Oosthuizen, Francois; Sumner, Nathan

    2016-01-01

    β-Methylphenylethylamines are positional isomers of amphetamines and have been discovered in sporting supplements. Although the fragmentation of the β-methylphenylethylamine and N-methyl-β-methylphenylethylamine in gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) systems is significantly different to their amphetamine and methylamphetamine isomers, under electrospray ionization commonly used in liquid chromatography-mass spectrometry (LC-MS) systems, the fragmentation of each of the isomeric pairs is almost identical. The similarities in fragmentation make it possible for the misidentification of the β-methylphenylethylamines as the illicit amphetamines. It is proposed that the similarities are due to a fragmentation pathway involving a common phenonium ion intermediate. By careful control of fragmentation energies in liquid chromatography-tandem mass spectrometry (LC-MS/MS) systems and/or close examination of the relative abundances of product ions formed by collision-induced dissociation (qualifier ratios), it is possible to distinguish the β-methylphenylethylamines from the amphetamines, even if significant retention time separation is not achieved. In liquid chromatography-electrospray ionization-quadrupole time of flight (LC-ESI-QTOF) systems the mass spectra of the β-methylphenylethylamines are identical to their amphetamine isomers. In such systems, retention time separation of the isomers is critical to avoid misidentification. During this study β-methylphenylethylamine and N-methyl-β-methylphenylethylamine have been identified in commercially available sporting supplements and oral fluid samples taken during the course of road-side drugs-in-drivers and workplace testing programmes. Copyright © 2015 John Wiley & Sons, Ltd.

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

    Directory of Open Access Journals (Sweden)

    Hedi Schelleman

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  12. 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.

  13. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

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

    Science.gov (United States)

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

    2013-04-01

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

  15. Repeating the Past

    Science.gov (United States)

    Moore, John W.

    1998-05-01

    As part of the celebration of the Journal 's 75th year, we are scanning each Journal issue from 25, 50, and 74 years ago. Many of the ideas and practices described are so similar to present-day "innovations" that George Santayana's adage (1) "Those who cannot remember the past are condemned to repeat it" comes to mind. But perhaps "condemned" is too strong - sometimes it may be valuable to repeat something that was done long ago. One example comes from the earliest days of the Division of Chemical Education and of the Journal.

  16. 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...

  17. All-optical repeater.

    Science.gov (United States)

    Silberberg, Y

    1986-06-01

    An all-optical device containing saturable gain, saturable loss, and unsaturable loss is shown to transform weak, distorted optical pulses into uniform standard-shape pulses. The proposed device performs thresholding, amplification, and pulse shaping as required from an optical repeater. It is shown that such a device could be realized by existing semiconductor technology.

  18. Bidirectional Manchester repeater

    Science.gov (United States)

    Ferguson, J.

    1980-01-01

    Bidirectional Manchester repeater is inserted at periodic intervals along single bidirectional twisted pair transmission line to detect, amplify, and transmit bidirectional Manchester 11 code signals. Requiring only 18 TTL 7400 series IC's, some line receivers and drivers, and handful of passive components, circuit is simple and relatively inexpensive to build.

  19. Withdrawal from Chronic Amphetamine Produces Persistent Anxiety-like Behavior but Temporally-Limited Reductions in Monoamines and Neurogenesis in the Adult Rat Dentate Gyrus.

    Science.gov (United States)

    Barr, Jeffrey L.; Renner, Kenneth J.; Forster, Gina L.

    2010-01-01

    Acute amphetamine administration activates monoaminergic pathways and increases systemic corticosterone, both of which influence anxiety states and adult dentate gyrus neurogenesis. Chronic amphetamine increases anxiety states in rats when measured at 24 hours and at 2 weeks of withdrawal. However, the effects of chronic amphetamine exposure and withdrawal on long term anxiety-like behavior and adult neurogenesis in the dentate gyrus are unknown. Adult male rats were administered amphetamine (2.5 mg/kg, ip.) daily for two weeks. Anxiety-like behaviors were increased markedly in amphetamine-treated rats following four weeks of withdrawal from amphetamine. Plasma corticosterone level was unaltered by amphetamine treatment or withdrawal. However, norepinephrine and serotonin concentrations were selectively reduced in the dentate gyrus 20 hours following amphetamine treatment. This effect did not persist through the four-week withdrawal period. In separate experiments, rats received bromodeoxyuridine to label cells in S-phase, prior to or immediately following amphetamine treatment. Newly generated cells were quantified to measure extent of progenitor cell proliferation and neurogenesis following treatment or withdrawal. Progenitor cell proliferation and neurogenesis were not significantly affected by amphetamine exposure when measured 20 hours following the last amphetamine treatment. However, neurogenesis in the dentate gyrus was reduced after four weeks of withdrawal when compared to saline-pretreated rats. Overall, our findings indicate that withdrawal from chronic amphetamine leads to persistent anxiety-like behavior which may be maintained by reduced neurogenesis in the dentate gyrus at this protracted withdrawal time point. However, neurogenesis is unaffected at earlier withdrawal time points where anxiety states emerge, suggesting different mechanisms may underlie the emergence of anxiety states during amphetamine withdrawal. PMID:20638943

  20. The Efficacy of Amphetamines for 64 Hours of Sustained Operations

    Science.gov (United States)

    2000-03-01

    effects attributable to Dexedrine; functions of polyphasic and ultrashort sleep , however, one subject evidenced increased diastolic 217-244. Boston...the Adaptability to Irregular Rest-Work Rhythms/Status of the Use of Drugs in Sleep -Wakefulness Management [les Differences entre individus concernant...system (CNS) stimulant that improves of the usefulness of dextroamphetamine beyond 40- alertness and postpones the need for sleep . In aviation, hour

  1. A case story, involving the use of maltitol, a sugar alcohol, as a cutting agent in amphetamine and cocaine powders

    DEFF Research Database (Denmark)

    Reitzel, Lotte Ask; Holm, Niels Bjerre; Linnet, Kristian;

    2016-01-01

    In a criminal case involving cutting and resale of amphetamine and cocaine in the Copenhagen area of Denmark, maltitol was used as a cutting agent. The analysis of maltitol in seizures of pure diluents as well as in amphetamine and cocaine powders was carried out using reversed-phase high...... performance liquid chromatography (HPLC) with high-resolution (HR) mass spectrometric detection. Maltitol was identified in four out of nine amphetamine samples and in five out of six cocaine samples from the case in question. The use of maltitol as a cutting agent was considered by the police as a specific...... marker of the particular criminal group under investigation. To support or reject this hypothesis, cocaine and amphetamine samples from a four month period after the involved persons had been arrested were evaluated, also as part of the police investigation. None of these samples contained maltitol...

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  3. Latent inhibition is disrupted by acute and repeated administration of corticosterone.

    Science.gov (United States)

    Shalev, U.; Feldon, J.; Weiner, I.

    1998-12-01

    Latent inhibition (LI), namely, a retardation in conditioning to a stimulus, as a consequence of its prior non- reinforced pre-exposure, is disrupted in amphetamine-treated rats and humans and in some subsets of schizophrenic patients. One factor that has been repeatedly implicated in precipitating and/or exacerbating psychotic episodes is stress. Since a principal biological response to stress is the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, leading, as its end product, to the secretion of corticosterone, the present experiments tested whether increase in corticosterone levels following exogenous corticosterone administration would disrupt LI. Both repeated (Experiment 1) and acute (Experiment 2) administration of corticosterone led to LI disruption, providing evidence for the involvement of the HPA axis alterations in LI and further supporting the viability of disrupted LI as an animal model of psychosis. Both regimens also increased amphetamine-induced activity. We suggest that disrupted LI may reflect a cognitive mechanism whereby prolonged periods of increased corticosterone levels can lead to 'sensory flooding' characteristic of psychosis.

  4. 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...

  5. Amphetamine-related mental disorder%精神活性物质所致精神障碍

    Institute of Scientific and Technical Information of China (English)

    陈晗晖; 何燕玲; 诸索宇; 赵敏

    2011-01-01

    @@ 1 病史摘要 患者,男,35岁,因 "反复使用冰毒4年,易激惹2个月,猜疑,耳闻人语伴失眠10 d" 第二次入住上海市精神卫生中心戒毒科.患者于2006年在朋友影响下,因好奇开始吸食冰毒(甲基苯丙胺),当时人很兴奋,不停地说话.最初1 ~2个月才使用一次.2007年使用频率增加,有时隔几天一次,后来几乎每天使用,每次1 ~6条,剂量不等.%A 35-year-old male with a 4-year history of amphetamine abuse was admitted after l0 days of psychotic symptoms.The symptoms resolved after 10 days of treatment with olanzapine and he remained abstinent from amphetamine use for 5 months after discharge, as verified by urine tests at three clinic visits. This case is used to discuss several related issues: the source and classification of amphetamine drugs, the prevalence of amphetamine abuse in youth, the differential diagnosis in drug abusers, clinical problems in managing amphetamine abuse, and the mechanisms underlying the brain changes associated with amphetamine use.

  6. Routine analysis of amphetamine class drugs as their naphthaquinone derivatives in human urine by high-performance liquid chromatography.

    Science.gov (United States)

    Talwar, D; Watson, I D; Stewart, M J

    1999-12-10

    We describe a simple HPLC method which is suitable for the routine confirmation of immunoassay positive amphetamine urine samples. The precolumn derivisation method employing sodium naphthaquinone-4-sulphonate was found to have adequate sensitivity, selectivity and precision for the measurement of amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxyethylamphetamine (MDEA) at 500 microg/l cutoff level for confirmatory analysis of amphetamines in urine. The specificity of the method is enhanced by detecting the peaks at two different wavelengths. The ratios of the peak heights measured at the two wavelengths were different for each of the 5 amphetamines analysed. There was no interference from other phenylethylamine analogues that are commonly found in "over the counter" preparations. The HPLC method is compared to a commercial TLC system for detecting amphetamines in urine of drug abusers attending drug rehabilitation programmes. The HPLC confirmatory method described is a viable alternative to GC or to the more complex and costly GC-MS techniques for confirming amphetamine, methamphetamine, MDMA, MDA and MDEA in urine of drug abusers especially when used in a clinical care setting.

  7. Individual differences in timing of peak positive subjective responses to d-amphetamine: Relationship to pharmacokinetics and physiology.

    Science.gov (United States)

    Smith, Christopher T; Weafer, Jessica; Cowan, Ronald L; Kessler, Robert M; Palmer, Abraham A; de Wit, Harriet; Zald, David H

    2016-04-01

    Rate of delivery of psychostimulants has been associated with their positive euphoric effects and potential addiction liability. However, information on individual differences in onset of d-amphetamine's effects remains scarce. We examined individual differences in the time to peak subjective and physiological effects and the pharmacokinetics/pharmacodynamics of oral d-amphetamine. We considered two independent studies that used different dosing regimens where subjects completed the drug effects questionnaire at multiple time points post d-amphetamine. Based on the observation of distinct individual differences in time course of drug effects questionnaire "feel", "high", and "like" ratings (DEQH+L+F) in Study 1, subjects in both studies were categorized as early peak responders (peak within 60 minutes), late peak responders (peak > 60 minutes) or nonresponders; 20-25% of participants were categorized as early peak responders, 50-55% as late peak responders and 20-30% as nonresponders. Physiological (both studies) and plasma d-amphetamine (Study 1) were compared among these groups. Early peak responders exhibited an earlier rise in plasma d-amphetamine levels and more sustained elevation in heart rate compared to late peak responders. The present data illustrate the presence of significant individual differences in the temporal pattern of responses to oral d-amphetamine, which may contribute to heightened abuse potential.

  8. Adolescent Female Cannabinoid Exposure Diminishes the Reward-Facilitating Effects of Δ9-Tetrahydrocannabinol and d-Amphetamine in the Adult Male Offspring

    Directory of Open Access Journals (Sweden)

    George Panagis

    2017-04-01

    Full Text Available Marijuana is currently the most commonly abused illicit drug. According to recent studies, cannabinoid use occurring prior to pregnancy can impact brain plasticity and behavior in future generations. The purpose of the present study was to determine whether adolescent exposure of female rats to Δ9-tetrahydrocannabinol (Δ9-THC induces transgenerational effects on the reward-facilitating effects of Δ9-THC and d-amphetamine in their adult male offspring. Female Sprague-Dawley rats received Δ9-THC (0.1 or 1 mg/kg, i.p. or vehicle during postnatal days 28–50. As adults, females were mated with drug-naïve males. We then assessed potential alterations of the Δ9-THC’s (0, 0.1, 0.5, and 1 mg/kg, i.p. and d-amphetamine’s (0, 0.1, 0.5, and 1 mg/kg, i.p. reward-modifying effects using the curve-shift variant of the intracranial self-stimulation (ICSS procedure in their adult male F1 offspring. The reward-facilitating effect of the 0.1 mg dose of Δ9-THC was abolished in the F1 offspring of females that were exposed to Δ9-THC (0.1 or 1 mg/kg, whereas the reward-attenuating effect of the 1 mg dose of Δ9-THC remained unaltered. The reward-facilitating effects of 0.5 and 1 mg of d-amphetamine were significantly decreased in the F1 offspring of females that were exposed to Δ9-THC (1 mg/kg and 0.1 or 1 mg, respectively. The present results reveal that female Δ9-THC exposure during adolescence can diminish the reward-facilitating effects of Δ9-THC and d-amphetamine in the adult male offspring. These transgenerational effects occur in the absence of in utero exposure. It is speculated that Δ9-THC exposure during female adolescence may affect neural mechanisms that are shaping reward-related behavioral responses in a subsequent generation, as indicated by the shifts in the reward-facilitating effects of commonly used and abused drugs.

  9. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

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

    Directory of Open Access Journals (Sweden)

    Tatyana D Sotnikova

    2005-08-01

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

  11. Methylphenidate amplifies the potency and reinforcing effects of amphetamines by increasing dopamine transporter expression.

    Science.gov (United States)

    Calipari, Erin S; Ferris, Mark J; Salahpour, Ali; Caron, Marc G; Jones, Sara R

    2013-01-01

    Methylphenidate (MPH) is commonly diverted for recreational use, but the neurobiological consequences of exposure to MPH at high, abused doses are not well defined. Here we show that MPH self-administration in rats increases dopamine transporter (DAT) levels and enhances the potency of MPH and amphetamine on dopamine responses and drug-seeking behaviours, without altering cocaine effects. Genetic overexpression of the DAT in mice mimics these effects, confirming that MPH self-administration-induced increases in DAT levels are sufficient to induce the changes. Further, this work outlines a basic mechanism by which increases in DAT levels, regardless of how they occur, are capable of increasing the rewarding and reinforcing effects of select psychostimulant drugs, and suggests that individuals with elevated DAT levels, such as ADHD sufferers, may be more susceptible to the addictive effects of amphetamine-like drugs.

  12. Structural elucidation of an uncommon phenylethylamine analogue in urine responsible for discordant amphetamine immunoassay results.

    Science.gov (United States)

    Marson, C; Schneider, S; Meys, F; Wennig, R

    2000-01-01

    The present paper describes investigations following the analysis of a urine specimen containing important amounts of an unknown substance detected by gas chromatography-mass spectrometry (GC-MS) analysis. FPIA analysis was positive (cutoff 0.3 mg/L) and Triage 8 rapid test was negative (cutoff 1 mg/L) for amphetamines. Considering the GC-MS spectrum, two different molecules, for example, N-ethyl-1-(3,4-methylenedioxyphenyl)ethylamine (1) or N-ethyl-4-methoxyamphetamine (2), have been suspected. Synthesis of these two compounds was carried out together with spectral (MS, 1H and 13C NMR, IR, UV) and chromatographic (GC) characterization as well as determination of immunological cross reactivities (FPIA and Triage 8). The unknown compound present in the urine specimen has been finally identified as N-ethyl-4-methoxyamphetamine (2), an uncommon amphetamine analogue.

  13. 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.

  14. Inhibition of glycogen synthase kinase-3 by SB 216763 affects acquisition at lower doses than expression of amphetamine-conditioned place preference in rats.

    Science.gov (United States)

    Wickens, Rebekah H; Quartarone, Susan E; Beninger, Richard J

    2016-12-14

    Dopamine (DA) drives incentive learning, whereby neutral stimuli acquire the ability to elicit responses. DA influences the signaling molecule glycogen synthase kinase-3 (GSK3). Inhibition of GSK3 attenuates the development of behavioral sensitization to stimulant drugs and conditioned place preference (CPP), a measure of incentive learning. We examined the role of GSK3 in the nucleus accumbens (NAc) of rats in CPP produced by amphetamine (1.5 mg/kg, i.p. or 20.0 μg/0.5 μl/side intra-NAc) by administering the inhibitor SB 216763 (1.0, 2.0, and 2.5 mg/kg, i.p. or 0.03, 0.30, 3.00, and 5.00 μg/0.5 μl/side intra-NAc) during acquisition or expression. We hypothesized a dose-dependent effect of SB 216763 and that acquisition would be affected by smaller doses than expression. For the systemic groups, 1.0 mg/kg of SB 216763 did not block CPP; 2.0 mg/kg administered in acquisition but not expression blocked CPP; and 2.5 mg/kg administered in either phase blocked CPP. For the central groups, 0.03 μg/0.5 μl/side of SB 216763 prevented acquisition but not expression, whereas larger doses administered in either phase blocked CPP. Thus, systemic or NAc inhibition of GSK3 by SB 216763 during acquisition or expression blocks amphetamine-produced CPP and acquisition is sensitive to lower doses than expression.

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

    Science.gov (United States)

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

    2014-05-01

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

  16. Keto amphetamine toxicity-focus on the redox reactivity of the cathinone designer drug mephedrone.

    Science.gov (United States)

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

    2014-09-01

    The β-keto amphetamine (cathinone, β-KA) designer drugs such as mephedrone (4-methylmethcathinone, 4-MMC) show a large degree of structural similarity to amphetamines like methamphetamine (METH). However, little is currently known about whether these substances also share the potential neurotoxic properties of their non-keto amphetamine counterparts, or what mechanisms could be involved. Here, we evaluate the cytotoxicity of β-KAs in SH-SY5Y cells using lactate dehydrogenase (LDH) assays, assess the redox potential of a range of β-KAs and non-keto amphetamines using the sensitive redox indicator 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1), and explore the effect of 4-MMC on the formation of protein adducts using ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) and on the mitochondrial respiratory chain using high-resolution respirometry. We show that treatment with β-KAs increases LDH release. Further, we demonstrate that even under physiological pH, β-KAs are effective and selective-as compared with their non-keto analogues-reductants in the presence of electron acceptors. Increased pH (range 7.6-8.0) greatly enhanced the reactivity up to sixfold. We found no evidence of protein adduct formation, suggesting the reactivity is due to direct electron transfer by the β-KAs. Finally, we show that 4-MMC and METH produce dissimilar effects on the respiratory chain. Our results indicate that β-KAs such as 4-MMC possess cytotoxic properties in vitro. Furthermore, in the presence of an electron-accepting redox partner, the ketone moiety of β-KAs is vital for pH-dependent redox reactivity. Further work is needed to establish the importance of β-KA redox properties and its potential toxicological importance in vivo.

  17. Adolescent mice are more vulnerable than adults to single injection-induced behavioral sensitization to amphetamine

    OpenAIRE

    Kameda, Sonia Regina; Fukushiro, Daniela Fukue [UNIFESP; Trombin, Thaís Fernanda [UNIFESP; Procopio-Souza, Roberta [UNIFESP; Patti, Camilla de Lima [UNIFESP; Hollais, André Willian [UNIFESP; Calzavara, Mariana Bendlin [UNIFESP; Abílio, Vanessa Costhek [UNIFESP; Ribeiro, Rosana de Alencar [UNIFESP; Tufik, Sergio; D'Almeida, Vânia; Frussa Filho, Roberto [UNIFESP

    2011-01-01

    Drug-induced behavioral sensitization in rodents has enhanced our understanding of why drugs acquire increasing motivational and incentive value. Compared to adults, human adolescents have accelerated dependence courses with shorter times from first exposure to dependence. We compared adolescent and adult mice in their ability to develop behavioral sensitization to amphetamine following a single injection. Adult (90-day-old) and adolescent (45-day-old) male Swiss mice received an acute intrap...

  18. 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.

  19. Impulsive choice and environmental enrichment: effects of d-amphetamine and methylphenidate.

    Science.gov (United States)

    Perry, Jennifer L; Stairs, Dustin J; Bardo, Michael T

    2008-11-03

    Individual differences in impulsive choice and rearing in differential environments are factors that predict vulnerability to drug abuse. The present study determined if rearing influences impulsive choice, and if d-amphetamine or methylphenidate alters impulsive choice in differentially reared rats. Male Sprague-Dawley rats were raised from 21 days of age in either an enriched condition (EC) or an isolated condition (IC) and were tested as young adults on an adjusting delay task. In this task, two levers were available and a response on one lever yielded one 45mg food pellet immediately, whereas a response on the other yielded three pellets after an adjusting delay. The delay was initially set at 6s, and it decreased or increased by 1s following responses on the immediate or delayed levers, respectively. A mean adjusted delay (MAD) was calculated upon completion of each daily session, and it served as the quantitative measure of impulsivity. Once MADs stabilized, rats were injected with saline, d-amphetamine (0.5, 1.0, or 2.0mg/kg, s.c.), or methylphenidate (2.5, 5.0, or 10.0mg/kg, s.c.) 15min prior to adjusting delay sessions. EC rats had higher baseline MADs (were less impulsive) than IC rats. Additionally, administration of d-amphetamine, but not methylphenidate, dose-dependently increased impulsive choice (decreased MADs) in EC rats. In IC rats, d-amphetamine and methylphenidate dose-dependently decreased impulsivity (increased MADs). These results indicate that rearing environment influences impulsive choice and moderates the effect of psychostimulants on impulsive choice. Specifically, psychostimulants may decrease environment-dependent impulsive choice in individuals with high levels of impulsivity (e.g., those with ADHD), whereas they may increase impulsive choice in individuals with low levels of impulsivity.

  20. Post-training, but not post-reactivation, administration of amphetamine and anisomycin modulates Pavlovian conditioned approach.

    Science.gov (United States)

    Blaiss, Cory A; Janak, Patricia H

    2007-05-01

    The psychostimulant, amphetamine (AMPH), and the protein synthesis inhibitor, anisomycin (ANI), have been shown to modulate the consolidation and reconsolidation of several types of learning. To determine whether Pavlovian conditioned approach (PCA) is modulated in a similar manner, we examined the effects of post-training and post-reactivation administration of both AMPH and ANI on memory for PCA. Male Long-Evans rats received PCA training sessions during which presentations of a CS+ were followed by sucrose delivery. AMPH (1 mg/kg, s.c.) injected immediately but not 6h after the first training session enhanced PCA behavior. ANI (150 mg/kg, s.c.) injected immediately but not 3h after the first training session impaired PCA behavior. This impairment was not due to the development of a conditioned taste aversion. To examine whether PCA can also be modulated by post-reactivation administration of AMPH and ANI, rats were given an injection of AMPH, ANI, or vehicle immediately after a memory reactivation session. Upon testing, the behavior of both the AMPH- and the ANI-treated rats was unaffected. This result remained consistent when the experiment was repeated with changes to various behavioral parameters (i.e., amount of training, length of memory reactivation). These findings indicate that AMPH and ANI act during the post-training but not the post-reactivation period to enhance and impair, respectively, the learning of PCA. This suggests that the consolidation of PCA can be modulated in a manner comparable to other types of learned associations, but once learned, the memory appears to be relatively robust and stable.

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

    Science.gov (United States)

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

    2016-11-01

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

  2. 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.

  3. Determination of amphetamines in biological samples using electro enhanced solid-phase microextraction-gas chromatography.

    Science.gov (United States)

    Zeng, Jingbin; Chen, Jingjing; Li, Min; Subhan, Fazle; Chong, Fayun; Wen, Chongying; Yu, Jianfeng; Cui, Bingwen; Chen, Xi

    2015-09-01

    In this work, an ordered mesoporous carbon (OMC)/Nafion coated fiber for solid-phase microextraction (SPME) was prepared and used as the working electrode for electro-enhanced SPME (EE-SPME) of amphetamines. The EE-SPME strategy is primarily based on the electro-migration and complementary charge interaction between fiber coating and ionic compounds. Compared with traditional SPME, EE-SPME exhibited excellent extraction efficiency for amphetamine (AP) and methamphetamine (MA) with an enhancement factor of 7.8 and 12.1, respectively. The present strategy exhibited good linearity for the determination of AP and MA in urine samples in the range of 10-1000ngmL(-1) and 20-1000ngmL(-1), respectively. The detection limits were found to be 1.2ngmL(-1) for AP and 4.8ngmL(-1) for MA. The relative standard deviations were calculated to be 6.2% and 8.5% for AP and MA, respectively. Moreover, the practical application of the proposed method was demonstrated by analyzing the amphetamines in urine and serum samples with satisfactory results.

  4. Application of solvent microextraction to the analysis of amphetamines and phencyclidine in urine.

    Science.gov (United States)

    Casari, C; Andrews, A R

    2001-09-01

    A fast and simple method to detect some commonly abused illicit drugs, amphetamine, methamphetamine, 3,4-methylendioxy-amphetamine (MDA), 3,4-methylendioxy-methamphetamine (MDMA), 3,4-methylendioxy-N-ethylamphetamine (MDEA) and phencyclidine (PCP) in urine using solvent microextraction (SME) combined with gas chromatography (GC) analysis has been developed. The extraction is conducted by suspending a 2 microl drop of chloroform in a 2 ml urine sample. Following 8 min of extraction, the organic solvent is withdrawn into the syringe and injected into a GC with a pulsed discharge helium ionization detector (PDHID). The effects of different extraction solvents and times, pH and sample preparation were studied. The optimized method was capable of detecting drugs in urine at concentrations below Substance Abuse and Mental Health Services Administration (SAMHSA) established cut-off values for preliminary testing. Good linearity and reproducibility of extraction were obtained. The limits of detection were 0.5 microg/ml for amphetamine, 0.1 microg/ml for methamphetamine and MDA, 0.05 microg/ml for MDMA, 0.025 microg/ml for MDEA and 0.015 microg/ml for PCP. Relative standard deviation (R.S.D.) values ranged between 5 and 20% for the studied drugs.

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

    Science.gov (United States)

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

    2008-03-01

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

  6. DPP IV inhibitor blocks mescaline-induced scratching and amphetamine-induced hyperactivity in mice.

    Science.gov (United States)

    Lautar, Susan L; Rojas, Camilo; Slusher, Barbara S; Wozniak, Krystyna M; Wu, Ying; Thomas, Ajit G; Waldon, Daniel; Li, William; Ferraris, Dana; Belyakov, Sergei

    2005-06-28

    Dipeptidyl peptidase IV (DPP IV) is a ubiquitous membrane-bound enzyme that cleaves the two N-terminal amino acids from peptides with a proline or alanine residue in the second position from the amino end. Potential substrates for DPP IV include several neuropeptides, suggesting a role for DPP IV in neurological processes. We have developed a potent DPP IV inhibitor (IC50 = 30 nM), 1-(2-amino-3-methyl-butyryl)-azetidine-2-carbonitrile (AMAC), which has shown efficacy in two established models of psychosis: mescaline-induced scratching and amphetamine-induced hyperactivity. In the mescaline-induced scratching model, AMAC treatment before mescaline administration reduced the number of scratching paroxysms by 68% (P < 0.01). The compound showed a dose-dependent effect, inhibiting significantly at 6, 20 and 60 mg/kg (37%, 39% and 68%, respectively). In the amphetamine-induced hyperactivity model, 50 and 60 mg/kg AMAC, given before injection of amphetamine, significantly reduced hyper-locomotion by 65% and 76%, respectively. Additionally, AMAC showed no significant activity in binding assays for 20 receptors thought to be involved in the pathology of schizophrenia, including dopamine, serotonin and glutamate. A structurally similar analog, 1-(2-dimethylamino-3-methyl-butyryl)-azetidine-2-carbonitrile (DAMAC), that does not inhibit DPP IV, was inactive in both models. Taken together, these data suggest that the antipsychotic effects of AMAC are the result of DPP IV inhibition.

  7. 大鼠肌紧张带重复低频电刺激后的生物力学及病理学改变%Biomechanical and pathological changes of taut bands in rats after repeated low-frequency electrical stimulation

    Institute of Scientific and Technical Information of China (English)

    王永慧; 孟菲; 丁欣利; 范真真; 王超; 岳寿伟

    2015-01-01

    Objective To investigate the biomechanical and pathological changes in vivo in the taut bands (TB) of biceps femoris in rats after repeated low-frequency electrical stimulation.Methods Twenty-eight Wistar rats were randomly divided into a control group,an electrical intensity-dependent fatigue group,which were subject to electric intensity-dependent fatigue test,and an electrical frequency-dependent fatigue group,which were subject to electrical frequency-dependent fatigue test.After fatigue tests,the taut band of the biceps femoris and the non-taut band of the contralateral biceps femoris were harvested for pathological observation.The maximum contraction force (MCF),electrical intensity-and frequency-dependent fatigue characteristics and any pathological changes in the TBs were assessed and compared to the non-taut band region of the other biceps femoris.Results The MCF at the 15th and 20th stimulation (1.42 ± 0.28 g and 0.93 ± 0.54 g respectively) were significantly lower than that at the 1 st and 5th stimulation of the TBs.High stimulation intensity (HSI) at the 15th and 20th stimulation (3.76 ± 0.71 V and 3.44 ± 0.97 V) were also significantly lower than at the 1st TB stimulation.At the 10th,15th and 20th stimulation of the TBs,MCF and HSI were both significantly lower than in the bands which were not tight.In the frequency-dependent fatigue stimulation tests,the frequency which generated the MCF of the TBs was significantly lower than in the bands which were not tight,while the MCF of the TBs was significantly higher than that of non-TBs.After either intensity or frequency fatigue testing,more severe edema,uneven cytoplasmic death and degeneration of muscle fibers were observed in sections from TBs than from the bands which were not tight.Conclusions Taut muscle bands are significantly less fatigue-resistant than normal muscle fibers.Taut bands may contribute to the fatigue of myofascial pain syndromes.%目的 研究大鼠肌紧张带(TB)重复低频电

  8. 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

    associated with these students consuming amphetamines. Materials and methods. A cross-sectional study was carried out, involving medical students from the Universidad de Manizales. The population consisted of 615 students who participated in probabilistic sampling, leading to 234 students being selected. An anonymous survey was used, leading to stimulant consumption and associated risk factors being identified. Results. 51.9% (44.9%-58.95 95%CI of the sample stated that they had taken amphetamines to improve their academic performance; 70.9% of them mentioned having achieved their objective. No relationship was found with classical risk factors such as anxiety, depression or family functionality. 87.9% of the students had not taken stimulants prior to entering the faculty. Students from the 6th, 7th, 8th and 9th semesters had the highest consumption indices: 73.3%, 60%, 68.8% and 57.7% respectively. The reasons for taking amphetamines included academic motives (32.5% and staying awake (18.7%; 65.8% drank alcohol. Conclusions. The number of medical students from the Universidad de Manizales taking amphetamines to improve their academic performance is really alarming. Intervention is necessary and solutions must be proposed to have a positive impact on consumption indices.

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

    Science.gov (United States)

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

    2016-05-27

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

  10. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-01-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4 whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 16. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  11. Growth Stimulants

    OpenAIRE

    Matthews, Nyle J.

    1989-01-01

    A tiny pellet inserted under the skin of a calf's ear may increase weight gains as much as 15 to 20 percent. This same result would take years to accomplish through breeding and selection. These tiny pellets are growth stimulants. They are made of hormones that are constructed to slowly release minute amounts into the blood stream that stimulate the animal to produce natural body hormones. One of these hormones is a growth hormone. It regulates the rate of growth of the animal. Increasing the...

  12. Amphetamine and morphine may produce acute-withdrawal related hypoactivity by initially activating a common dopamine pathway.

    Science.gov (United States)

    White, Wesley; White, Ilsun M

    2016-10-15

    Rats given drugs of abuse such as amphetamine or morphine show longer-term effects, that is, signs of acute withdrawal, including hypoactivity, hypophagia, and blunted affect, sometime between 12 and 24h after treatment. This research explores the possibility that signs of acute withdrawal produced by different drugs of abuse are instigated by overlapping mechanisms. The specific objectives of the research were to see if amphetamine and morphine produced longer-term hypoactivity, and to see if any longer-term hypoactivity elicited by the drugs could be blocked by SCH23390, a dopamine D1 antagonist. Six groups of rats, with eight rats in each group, were exposed to a series of five-day tests. Near light onset of Test Day 1, each animal was given control administrations, consisting of a saline treatment (1.0ml/kg) followed 30m later by a saline posttreatment, and locomotor activity was monitored for the next 24h. On Test Day 3, each animal was given experimental administrations, and locomotor activity was again monitored for 24h. Each group received only one combination of experimental administrations across tests. Experimental administrations consisted of saline, amphetamine (2.0mg/kg), or morphine (5.0mg/kg), followed by saline or SCH23390 (0.05mg/kg). All administrations were subcutaneous. Amphetamine and morphine produced longer-term hypoactivity, having similar time courses and magnitudes. SCH23390 blocked the longer-term hypoactivity produced by both drugs. Saline and SCH23390 produced no changes in longer-term activity in their own right. The time course of amphetamine-elicited longer-term hypoactivity resembled that of amphetamine-elicited longer-term hypophagia observed in a prior study. Approximately 1/4 of the animals given amphetamine or morphine did not show longer-term hypoactivity ("low withdrawal" rats). Amphetamine and morphine may initiate the cascade of events resulting in signs of acute withdrawal by producing activation in a common pathway that

  13. Estimation of gamma-hydroxybutyrate (GHB) co-consumption in serum samples of drivers positive for amphetamine or ecstasy.

    Science.gov (United States)

    Lott, S; Musshoff, F; Madea, B

    2012-09-10

    There is no toxicological analysis of gamma-hydroxybutyrate (GHB) applied routinely in cases of driving under influence (DUI); therefore the extent of consumption of this drug might be underestimated. Its consumption is described as occurring often concurrently with amphetamine or ecstasy. This study examines 196 serum samples which were collected by police during road side testing for GHB. The samples subject to this study have already been found to be positive for amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and/or 3,4-methylenedioxyethamphetamine (MDEA). Analysis has been performed by LC/MS/MS in the multiple reaction monitoring (MRM) mode. Due to its polarity, chromatographic separation of GHB was achieved by a HILIC column. To differentiate endogenous and exogenous levels of GHB, a cut-off concentration of 4μg/ml was applied. Of the 196 samples, two have been found to be positive for GHB. Of these samples, one sample was also positive for amphetamine and one for MDMA. Whilst other amphetamine derivates were not detected in these samples, both samples were found to be positive for cannabinoids. These results suggest that co-consumption of GHB with amphetamine or ecstasy is relatively low (1%) for the collective of this study.

  14. Repeated administration of adenosine increases its cardiovascular effects in rats.

    Science.gov (United States)

    Vidrio, H; García-Márquez, F; Magos, G A

    1987-01-20

    Hypotensive and negative chronotropic responses to adenosine in anesthetized rats increased after previous administration of the nucleoside. Bradycardia after adenosine in the isolated perfused rat heart was also potentiated after repeated administration at short intervals. This self-potentiation could be due to extracellular accumulation of adenosine and persistent stimulation of receptors caused by saturation or inhibition of cellular uptake of adenosine.

  15. The role of 5-HT(2A) receptor antagonism in amphetamine-induced inhibition of A10 dopamine neurons in vitro

    NARCIS (Netherlands)

    Olijslagers, J.E.; Perlstein, B.; Werkman, T.R.; Mc.Creary, A.C.; Siarey, R.; Kruse, C.G.; Wadman, W.J.

    2005-01-01

    The role of the 5-HT(2A) receptor in modulating amphetamine-induced inhibition of dopamine neuronal firing in A9 and A10 was investigated in rat midbrain slices. The antipsychotic drugs olanzapine and clozapine more potently reversed the amphetamine-induced inhibition in A10 neurons compared to A9 n

  16. Lack of delayed effects of amphetamine, methoxamine, and prazosin (adrenergic drugs) on behavioral outcome after lateral fluid percussion brain injury in the rat.

    Science.gov (United States)

    Dose, J M; Dhillon, H S; Maki, A; Kraemer, P J; Prasad, R M

    1997-05-01

    This study examined the delayed effects of the administration of d-amphetamine, methoxamine (an alpha1-adrenergic receptor agonist), and prazosin (an alpha1-adrenergic receptor antagonist) on the behavioral outcome of lateral fluid-percussion (FP) brain injury. Rats trained to perform a beam-walking task were subjected to brain injury of moderate severity (2.1 to 2.2 atm). Twenty-four hours after injury, rats were treated with amphetamine, methoxamine, or prazosin at two or three different dose levels. Amphetamine-treated animals displayed no significant improvement in beam-walking ability either during or after drug intoxication (from days 3 to 5 after brain injury). Similarly, neither methoxamine nor prazosin significantly affected beam-walking ability during or after drug intoxication. Neither amphetamine treatment at three different doses nor treatment with methoxamine or prazosin at two different doses affected the spatial learning disabilities of brain-injured animals. These results suggest that (1) unlike amphetamine administration after sensorimotor cortex (SMC) ablation or contusion brain injury models, amphetamine administration at 24 h after concussive FP brain injury does not improve beam-walking performance; (2) unlike amphetamine administration 10 min after concussive FP brain injury amphetamine administration 24 h after injury does not improve cognitive function; and (3) unlike prazosin administration after SMC ablation brain injury, prazosin administration 24 h after concussive FP brain injury does not effect beam-walking performance.

  17. Clinical Values of Single or Repeated Triptorelin Stimulating Test in the Differential Diagnosis between Idiopathic Hypogonadotropic Hypogonadism and Constitutional Delayed Puberty%单次或重复曲普瑞林兴奋试验对特发性低促性腺激素性性腺功能减退症和体质性青春发育延迟鉴别诊断的作用

    Institute of Scientific and Technical Information of China (English)

    茅江峰; 伍学焱; 卢双玉; 聂敏

    2011-01-01

    Objective To investigate the values of single or repeated luteinizing hormone ( LH) releasing hormone analogue (triptorelin) stimulating test in the differential diagnosis between idiopathic hypogo-nadotropic hypogonadism (IHH) and constitutional delayed puberty (CDP). Methods Male patients (n -133 ) without puberty onset after the age of 14 were recruited for triptorelin stimulating test and were followed upfor 24 - 48 months until the diagnosis were confirmed: 86 were IHH and the other 47 were CDP. Repeated trip-torelin stimulating tests were conducted in 9 IHH patients and 13 CDP patients one year after the first stimulating tests with an attempt to evaluate the dynamic change of hypothalamus-pituitary-testis axis function. The relationship between the final diagnosis and the peak LH value ( Lhmax) , and the changes of repeated Lhmax were investigated. Results In the single triptorelin stimulating test, Lhmax was (1.9 ±1.2) U/L in IHH group, which was significantly lower than that in CDP group [ (13.7+8.3) U/L] ( P < 0. 01) ; 75 IHH patients (87. 2% ) had a Lhmax lower than 4 U/L, while only 2 CDP patients (4. 3% ) had a Lhmax lower than 4 U/L. When Lhmax <4U/L was used as a criteria for the diagnosis of IHH, the single triptorelin stimulating test had a sensitivity of 87. 2% , a specificity of 95. 1% , and a positive predictive value of 97. 4%. The repeated triptorelin stimulating tests performed one year later showed that the Lhmax in the 9 IHH patients increased from (4. 7 ± 2. 5 ) U/L to (5. 1 ± 3. 3 ) U/L ( P = 0. 78) , while that in the 13 CDP patients increased from (10. 7 + 3. 3) U/L to (24. 5 ± 5. 7) U/L (P < 0. 05). Conclusions A single triptorelin stimulating test is highly effective in differentiating IHH from CDP. For some patients without definitive diagnosis, a repeated triptorelin stimulating test performed one year later may provide more valuable information on the dynamic change of the hypothalamus-pituitary-testis axis function.%目的

  18. Surface-activated chemical ionization ion trap mass spectrometry in the analysis of amphetamines in diluted urine samples.

    Science.gov (United States)

    Cristoni, Simone; Bernardi, Luigi Rossi; Gerthoux, Piermario; Gonella, Elisabetta; Mocarelli, Paolo

    2004-01-01

    A new ionization method, named surface-activated chemical ionization (SACI), was employed for the analysis of five amphetamines (3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDE), amphetamine and methamphetamine) by ion trap mass spectrometry. The results so obtained have been compared with those achieved by using atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) using the same instrument, clearly showing that SACI is the most sensitive of the three. The limit of detection and linearity range for SACI were compared with those obtained using APCI and ESI, showing that the new SACI approach provides the best results for both criteria. SACI was used to analyze MDA, MDMA MDE, amphetamine and methamphetamine in four urine samples, and the quantitation results are compared with those achieved using ESI.

  19. 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

    The aim of this study was to develop a quantitative gas chromatography mass spectrometry (GC-MS) method to determine the classical amphetamines and their methylenedioxylated derivatives in human hair. The procedure involved liquid-liquid extraction of hydrolysed hair spiked with deuterated internal....../mg and of quantification from 0.24 to 0.46 ng/mg, depending on compound. The method was applied on 40 authentic hair samples (segmented or pooled hair), of which 15 cases involved amphetamine and/or ecstasy. The hair concentrations ranged from LOD to 3.2 ng/mg of AM in 7 cases, to 0.4 ng/mg of MDA in 3 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....

  20. 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 adulte......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...

  1. Effects of amphetamine, morphine, and CP 55, 940 on Go/No-Go task performance in rhesus monkeys.

    Science.gov (United States)

    Koek, Wouter; Gerak, Lisa R; France, Charles P

    2015-08-01

    In humans, impulsivity measured as false alarms in a Go/No-Go task is reportedly decreased by amphetamine and is not affected by oxycodone and delta(9)-tetrahydrocannabinol. To model these findings in animals, three rhesus monkeys were trained to perform a food-reinforced Go/No-Go task. In this task, amphetamine was found to decrease false alarms (i.e. responding during No-Go trials), but only at doses that also decreased hits (i.e. responding during Go trials). Morphine generally decreased hits but not false alarms. The cannabinoid receptor agonist CP 55, 940 decreased both false alarms and hits, but only at doses that also decreased the number of trials completed. Additional studies in animals and humans are necessary to delineate the conditions under which amphetamine and other psychoactive drugs affect impulsivity in Go/No-Go tasks.

  2. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters.

    Science.gov (United States)

    Hofmaier, Tina; Luf, Anton; Seddik, Amir; Stockner, Thomas; Holy, Marion; Freissmuth, Michael; Ecker, Gerhard F; Schmid, Rainer; Sitte, Harald H; Kudlacek, Oliver

    2014-07-01

    Psychostimulants such as amphetamine and cocaine are illicitly used drugs that act on neurotransmitter transporters for dopamine, serotonin or norepinephrine. These drugs can by themselves already cause severe neurotoxicity. However, an additional health threat arises from adulterant substances which are added to the illicit compound without declaration. One of the most frequently added adulterants in street drugs sold as cocaine is the anthelmintic drug levamisole. We tested the effects of levamisole on neurotransmitter transporters heterologously expressed in HEK293 cells. Levamisole was 100 and 300-fold less potent than cocaine in blocking norepinephrine and dopamine uptake, and had only very low affinity for the serotonin transporter. In addition, levamisole did not trigger any appreciable substrate efflux. Because levamisole and cocaine are frequently co-administered, we searched for possible allosteric effects; at 30μM, a concentration at which levamisole displayed already mild effects on norepinephrine transport it did not enhance the inhibitory action of cocaine. Levamisole is metabolized to aminorex, a formerly marketed anorectic drug, which is classified as an amphetamine-like substance. We examined the uptake-inhibitory and efflux-eliciting properties of aminorex and found it to exert strong effects on all three neurotransmitter transporters in a manner similar to amphetamine. We therefore conclude that while the adulterant levamisole itself has only moderate effects on neurotransmitter transporters, its metabolite aminorex may exert distinct psychostimulant effects by itself. Given that the half-time of levamisole and aminorex exceeds that of cocaine, it may be safe to conclude that after the cocaine effect "fades out" the levamisole/aminorex effect "kicks in".

  3. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters☆

    Science.gov (United States)

    Hofmaier, Tina; Luf, Anton; Seddik, Amir; Stockner, Thomas; Holy, Marion; Freissmuth, Michael; Ecker, Gerhard F.; Schmid, Rainer; Sitte, Harald H.; Kudlacek, Oliver

    2014-01-01

    Psychostimulants such as amphetamine and cocaine are illicitly used drugs that act on neurotransmitter transporters for dopamine, serotonin or norepinephrine. These drugs can by themselves already cause severe neurotoxicity. However, an additional health threat arises from adulterant substances which are added to the illicit compound without declaration. One of the most frequently added adulterants in street drugs sold as cocaine is the anthelmintic drug levamisole. We tested the effects of levamisole on neurotransmitter transporters heterologously expressed in HEK293 cells. Levamisole was 100 and 300-fold less potent than cocaine in blocking norepinephrine and dopamine uptake, and had only very low affinity for the serotonin transporter. In addition, levamisole did not trigger any appreciable substrate efflux. Because levamisole and cocaine are frequently co-administered, we searched for possible allosteric effects; at 30 μM, a concentration at which levamisole displayed already mild effects on norepinephrine transport it did not enhance the inhibitory action of cocaine. Levamisole is metabolized to aminorex, a formerly marketed anorectic drug, which is classified as an amphetamine-like substance. We examined the uptake-inhibitory and efflux-eliciting properties of aminorex and found it to exert strong effects on all three neurotransmitter transporters in a manner similar to amphetamine. We therefore conclude that while the adulterant levamisole itself has only moderate effects on neurotransmitter transporters, its metabolite aminorex may exert distinct psychostimulant effects by itself. Given that the half-time of levamisole and aminorex exceeds that of cocaine, it may be safe to conclude that after the cocaine effect “fades out” the levamisole/aminorex effect “kicks in”. PMID:24296074

  4. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Stiefel, Gary; Besag, Frank M C

    2010-10-01

    Attention-deficit hyperactivity disorder (ADHD) is a very common condition in children and often extends into the adult years. Drugs such as methylphenidate, amphetamines and atomoxetine are frequently prescribed as part of management. The use of these drugs has been increasing and significant clinical benefit is achieved but safety has been questioned. In this review, the cardiovascular safety of these drugs is examined with regard to effects on blood pressure (BP), heart rate (HR), ECG parameters and the risk of sudden death. Methylphenidate appears to cause minor increases in BP and HR. There are no strong data to suggest that methylphenidate increases the corrected QT interval (QTc). Amphetamines appear to cause minor increases in HR and BP over the long term. There is growing evidence to suggest that amphetamines do not cause statistically or clinically significant increases in QTc. Sudden death remains an extremely rare event and there is no clear evidence to attribute this to methylphenidate. Some data even suggest that the risk of sudden death in treated children may be less common than in the background population. Limited data suggest that atomoxetine may increase BP and HR in the short term; in the long term it appears to increase BP. The effects of atomoxetine on QTc remain uncertain. Use of this drug does not appear to be associated with sudden death. Because the current evidence is based on research that has not been specifically designed to investigate the cardiovascular effects of these drugs it is difficult to draw firm conclusions, and further work is required specifically to address these questions.

  5. [AWMF-guideline: cocaine-, amphetamine-, ecstasy- and hallucinogen-related disorders].

    Science.gov (United States)

    Thomasius, R; Gouzoulis-Mayfrank, E; Karus, C; Wiedenmann, H; Hermle, L; Sack, P M; Zeichner, D; Küstner, U; Schindler, A; Krüger, A; Uhlmann, S; Petersen, K U; Zapletalova, P; Wartberg, L; Schütz, C G; Schulte-Markwort, M; Obrocki, J; Heinz, A; Schmoldt, A

    2004-12-01

    Actually, guidelines for treatment of substance-related disorders were written under the overall control of the DG-Sucht e. V. and the DGPPN e. V. This appears within the framework of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaft (AWMF). The leading objective of these guidelines is the description of the current scientifically proven and evidence-based medicine in addiction to derive recommendations to therapy. In this context, the guideline for treatment of cocaine-, amphetamine-, ecstasy-, and halluzinogen-related disorders is introduced.

  6. -Amphetamine and Antipsychotic Drug Effects on Latent Inhibition in Mice Lacking Dopamine D2 Receptors

    OpenAIRE

    Bay-Richter, C.; O'Callaghan, M J; N Mathur; O'Tuathaigh, C.M.P.; Heery, D M; Fone, K C F; Waddington, J. L.; Moran, P.M.

    2013-01-01

    Drugs that induce psychosis, such as -amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D2 (D2). All antipsychotic drugs are D2 antagonists, but D2 antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D2 is necessary for their behavioral effects. Using D2-null mice (Drd 2 −/−), we first investigated whether D2 is required for AMP disruption ...

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

    Science.gov (United States)

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

    2014-01-01

    A GC-MS method for simultaneous analysis of cocaine (COC), amphetamines (AMPs), opiates, cannabinoids and their metabolites in vitreous humor (VH) was developed and fully validated. VH samples were extracted using solid phase extraction and injected into the GC-MS, using a selected ion monitoring mode. Linearity ranged from 10 to 1000 ng/mL; the exception was anhydroecgonine methyl ester (AEME), for which linearity ranged from 10 to 750 ng/mL. Inter-assay imprecision lay from 1.2 to 10.0%, intra-assay imprecision was opiates and their metabolites.

  8. Delusional Parasitosis in a Female Treated with Mixed Amphetamine Salts: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Martha Buscarino

    2012-01-01

    Full Text Available Objectives. To explore factors underlying the onset of delusional parasitosis; a condition in which an individual has a fixed, false belief that he/she is infested with insects. Case Description. MJ is a 57-year-old female who presents with symptoms of fatigue and AD/HD. Upon treatment with extended release mixed amphetamine salts, the patient displayed symptoms of delusional parasitosis. After eventual discontinuation of this medication, her delusions resolved. Comments. In order to maintain confidentiality, all identifying information was removed. To this end, please note that MJ is a fictitious name.

  9. Determination of amphetamine and methylphenidate in exhaled breath of patients undergoing attention-deficit/hyperactivity disorder treatment.

    Science.gov (United States)

    Beck, Olof; Stephanson, Niclas; Sandqvist, Sören; Franck, Johan

    2014-08-01

    It has been discovered recently that exogenous substances are detectable in exhaled breath after intake. Exhaled breath therefore constitutes a new possible matrix in clinical pharmacology and toxicology. The present work was aimed at exploring this possibility further by a study on patients treated for attention-deficit/hyperactivity disorder with D-amphetamine and methylphenidate. Thirteen patients (age range: 32-61 years; 5 women) were included in the study, and breath and urine samples were collected at different times in the dose interval. Analyses of breath and urine samples were done with liquid chromatography-mass spectrometry methods. Urine was examined for amphetamine, methylphenidate, and its metabolite ritalinic acid. Among the 9 patients who received D-amphetamine medication in daily doses of 20-100 mg, amphetamine was detected in all subjects in amounts ranging from 1200 to 30,800 picogram per filter. Among 8 patients receiving methylphenidate medication in daily doses of 80-400 mg, it was detected and quantified in 7 of the cases in amounts ranging from 150 to 10,400 picogram per filter and ritalinic acid was detected and quantified in 3 of the cases ranging from 35 to 360 picogram per filter. In 1 case, methylphenidate was only detectable in breath and urine, whereas ritalinic acid was quantifiable in urine, which could indicate noncompliance, with the 4 hours of dose regimen prescribed. In a number of cases, the sampling was performed 24 hours after the last dose intake. Identification of amphetamine and methylphenidate was based on correct chromatographic retention time and correct product ion ratio with detection performed in selected reaction monitoring mode. The results confirm that amphetamine is present in exhaled breath after intake and demonstrate for the first time the presence of methylphenidate and ritalinic acid after its intake. This gives further support to the potential use of exhaled breath for detecting drug intake.

  10. Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review

    Directory of Open Access Journals (Sweden)

    Westover Arthur N

    2012-06-01

    Full Text Available Abstract Background There is increasing concern that prescription stimulants may be associated with adverse cardiovascular events such as stroke, myocardial infarction, and sudden death. Public health concerns are amplified by increasing use of prescription stimulants among adults. Methods The objective of this study was to conduct a systematic review of the evidence of an association between prescription stimulant use and adverse cardiovascular outcomes. PUBMED, MEDLINE, EMBASE and Google Scholar searches were conducted using key words related to these topics (MESH: ADHD; Adults; Amphetamine; Amphetamines; Arrhythmias, Cardiac; Cardiovascular Diseases; Cardiovascular System; Central Nervous Stimulants; Cerebrovascular; Cohort Studies; Case–control Studies; Death; Death, Sudden, Cardiac; Dextroamphetamine; Drug Toxicity; Methamphetamine; Methylphenidate; Myocardial Infarction; Stimulant; Stroke; Safety. Eligible studies were population-based studies of children, adolescents, or adults using prescription stimulant use as the independent variable and a hard cardiovascular outcome as the dependent variable. Results Ten population-based observational studies which evaluated prescription stimulant use with cardiovascular outcomes were reviewed. Six out of seven studies in children and adolescents did not show an association between stimulant use and adverse cardiovascular outcomes. In contrast, two out of three studies in adults found an association. Conclusions Findings of an association between prescription stimulant use and adverse cardiovascular outcomes are mixed. Studies of children and adolescents suggest that statistical power is limited in available study populations, and the absolute risk of an event is low. More suggestive of a safety signal, studies of adults found an increased risk for transient ischemic attack and sudden death/ventricular arrhythmia. Interpretation was limited due to differences in population, cardiovascular outcome

  11. Histone deacetylase complexes promote trinucleotide repeat expansions.

    Directory of Open Access Journals (Sweden)

    Kim Debacker

    2012-02-01

    Full Text Available Expansions of DNA trinucleotide repeats cause at least 17 inherited neurodegenerative diseases, such as Huntington's disease. Expansions can occur at frequencies approaching 100% in affected families and in transgenic mice, suggesting that specific cellular proteins actively promote (favor expansions. The inference is that expansions arise due to the presence of these promoting proteins, not their absence, and that interfering with these proteins can suppress expansions. The goal of this study was to identify novel factors that promote expansions. We discovered that specific histone deacetylase complexes (HDACs promote CTG•CAG repeat expansions in budding yeast and human cells. Mutation or inhibition of yeast Rpd3L or Hda1 suppressed up to 90% of expansions. In cultured human astrocytes, expansions were suppressed by 75% upon inhibition or knockdown of HDAC3, whereas siRNA against the histone acetyltransferases CBP/p300 stimulated expansions. Genetic and molecular analysis both indicated that HDACs act at a distance from the triplet repeat to promote expansions. Expansion assays with nuclease mutants indicated that Sae2 is one of the relevant factors regulated by Rpd3L and Hda1. The causal relationship between HDACs and expansions indicates that HDACs can promote mutagenesis at some DNA sequences. This relationship further implies that HDAC3 inhibitors being tested for relief of expansion-associated gene silencing may also suppress somatic expansions that contribute to disease progression.

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

    Science.gov (United States)

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

    2003-03-01

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

  13. Alterations in ventral and dorsal striatal allosteric A2AR-D2R receptor-receptor interactions after amphetamine challenge: Relevance for schizophrenia.

    Science.gov (United States)

    Pintsuk, Julia; Borroto-Escuela, Dasiel O; Lai, Terence K Y; Liu, Fang; Fuxe, Kjell

    2016-10-29

    Striatal dopamine D2R homodimerization is increased in the dorsal striatum after acute amphetamine challenge and in the amphetamine-induced sensitized state, a well-known animal model of schizophrenia. Therefore, it was tested if the increase in D2R homoreceptor complexes found after acute amphetamine challenge in the saline or the amphetamine sensitized state leads to changes in the antagonistic adenosine A2AR-D2R interactions in the striatum. [(3)H]-raclopride binding was performed in membrane preparations from the ventral and dorsal striatum involving competition with the D2R like agonist quinpirole. In the ventral striatum CGS 21680 produced a significant increase of the KiH values (pvalues in saline sensitized rats after amphetamine challenge. However, in the dorsal striatum a significant change did not develop in the KiH values when expressed in percent of the corresponding values in saline sensitized rats after amphetamine challenge. In fact, the non-significant change was in the opposite direction towards a reduction of the KiH values. Taken together, a reduced affinity of the high affinity D2 agonist binding site (KiH value) developed in the ventral but not in the dorsal striatum as a result of increased antagonistic allosteric A2AR-D2R interactions in the amphetamine-induced sensitized state versus the saline sensitized state after an acute amphetamine challenge. The selective reappearance of antagonistic A2AR-D2R receptor-receptor interactions in the ventral striatum after amphetamine challenge in the amphetamine sensitized rat may give one possible mechanism for the atypical antipsychotic-like actions of A2AR receptor agonists.

  14. 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 adulte......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...

  15. 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...... in 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....

  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...... in 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. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  18. DWI Repeaters and Non-Repeaters: A Comparison.

    Science.gov (United States)

    Weeber, Stan

    1981-01-01

    Discussed how driving-while-intoxicated (DWI) repeaters differed signigicantly from nonrepeaters on 4 of 23 variables tested. Repeaters were more likely to have zero or two dependent children, attend church frequently, drink occasionally and have one or more arrests for public intoxication. (Author)

  19. To Repeat or Not to Repeat a Course

    Science.gov (United States)

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  20. Bursting behaviours in cascaded stimulated Brillouin scattering

    Institute of Scientific and Technical Information of China (English)

    Liu Zhan-Jun; He Xian-Tu; Zheng Chun-Yang; Wang Yu-Gang

    2012-01-01

    Stimulated Brillouin scattering is studied by numerically solving the Vlasov-Maxwell system.A cascade of stimulated Brillouin scattering can occur when a linearly polarized laser pulse propagates in a plasma.It is found that a stimulated Brillouin scattering cascade can reduce the scattering and increase the transmission of light,as well as introduce a bursting behaviour in the evolution of the laser-plasma interaction.The bursting time in the reflectivity is found to be less than half the ion acoustic period.The ion temperature can affect the stimulated Brillouin scattering cascade,which can repeat several times at low ion temperatures and can be completely eliminated at high ion temperatures.For stimulated Brillouin scattering saturation,higher-harmonic generation and wave-wave interaction of the excited ion acoustic waves can restrict the amplitude of the latter.In addition,stimulated Brillouin scattering cascade can restrict the amplitude of the scattered light.

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

    Science.gov (United States)

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

    2013-03-01

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

  2. The Histaminergic Tuberomamillary Nucleus Is Involved in Appetite for Sex, Water and Amphetamine.

    Science.gov (United States)

    Contreras, Marco; Riveros, María E; Quispe, Maricel; Sánchez, Cristián; Perdomo, Guayec; Torrealba, Fernando; Valdés, José L

    2016-01-01

    The histaminergic system is one component of the ascending arousal system which is involved in wakefulness, neuroendocrine control, cognition, psychiatric disorders and motivation. During the appetitive phase of motivated behaviors the arousal state rises to an optimal level, thus giving proper intensity to the behavior. Previous studies have demonstrated that the histaminergic neurons show an earlier activation during the appetitive phase of feeding, compared to other ascending arousal system nuclei, paralleled with a high increase in arousal state. Lesions restricted to the histaminergic neurons in rats reduced their motivation to get food even after 24 h of food deprivation, compared with intact or sham lesioned rats. Taken together, these findings indicate that the histaminergic system is important for appetitive behavior related to feeding. However, its role in other goal-directed behaviors remains unexplored. In the present work, male rats rendered motivated to obtain water, sex, or amphetamine showed an increase in Fos-ir of histaminergic neurons in appetitive behaviors directed to get those reinforcers. However, during appetitive tests to obtain sex, or drug in amphetamine-conditioned rats, Fos expression increased in most other ascending arousal system nuclei, including the orexin neurons in the lateral hypothalamus, dorsal raphe, locus coeruleus and laterodorsal tegmental neurons, but not in the ventral tegmental area, which showed no Fos-ir increase in any of the 3 conditions. Importantly, all these appetitive behaviors were drastically reduced after histaminergic cell-specific lesion, suggesting a critical contribution of histamine on the intensity component of several appetitive behaviors.

  3. 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.

  4. Increasing food deprivation relative to baseline influences D-amphetamine dose-response gradients.

    Science.gov (United States)

    Lotfizadeh, Amin D; Zimmermann, Zachary J; Watkins, Erin E; Edwards, Timothy L; Poling, Alan

    2014-10-01

    Several studies using non-pharmacological discriminative stimuli have found that stimulus control, as evident in generalization gradients, changes when motivation for (i.e., deprivation of) the relevant reinforcer is altered. Drug-discrimination studies, however, have not consistently revealed such an effect. A procedural detail that may account for the lack of a reliable effect in drug-discrimination studies is that motivation was characteristically reduced relative to the training condition in these studies. The present experiment examined how substantially increasing motivation affects D-amphetamine discrimination. Rats initially were trained to discriminate D-amphetamine (1.0 mg/kg) from vehicle (0 mg/kg) injections under 22-h food deprivation conditions. Dose-response gradients were then obtained under 22-h and 46-h deprivation levels. The ED50 was significantly higher with greater deprivation. This finding suggests that increasing motivation relative to the training condition may reduce stimulus control by drugs, while decreasing it may sharpen stimulus control. Copyright © 2014. Published by Elsevier Inc.

  5. Effects of indorenate on food intake: a comparison with fenfluramine and amphetamine.

    Science.gov (United States)

    Velázquez Martínez, D N; Valencia Flores, M; López Cabrera, M; Villarreal, J E

    1995-01-01

    Indorenate (TR3369, 5-methoxytryptamine b-methylcarboxylate HCl) is a 5-HT1-like receptor agonist with hypotensive activity. Here, we describe that indorenate also decreases food intake (ED50 26.1 mg/kg) without an appreciable effect in water intake (the estimated ED50 for water was 589.8 mg/kg). The anorectic activity of indorenate was compared to the effects of amphetamine and other serotonin agonists; the effect of indorenate was smaller than those of the other compounds; however, the effect of indorenate was specific to food, whereas all the other drugs also produced significant decrements in water intake. The serotonin antagonists cinanserin, cyproheptadine, methergoline and methysergide effectively prevented the decrease in food intake produced by indorenate and fenfluramine. Haloperidol, a dopaminergic antagonist, was ineffective in preventing the effect of indorenate although it prevented the anorectic effect of amphetamine. The present results suggest the participation of serotoninergic, but not dopaminergic mechanisms, in the decrease in food intake produced by indorenate.

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

    Science.gov (United States)

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

    2014-01-01

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

  7. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  8. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  9. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  10. Spinal cord stimulation exerts neuroprotective effects against experimental Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Aiko Shinko

    Full Text Available In clinical practice, deep brain stimulation (DBS is effective for treatment of motor symptoms in Parkinson's disease (PD. However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS. We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz with an epidural electrode at C1-2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the

  11. The influence of acoustic and tactile stimulation on vegetative parameters and EEG in persistent vegetative state.

    Science.gov (United States)

    Keller, Ingo; Hülsdunk, Angelika; Müller, Friedemann

    2007-01-01

    In the present study, we investigated whether different kinds of stimulation in the persistent vegetative state (PVS) lead to specific patterns of physiological reactions. In addition, a possible effect of stimulating drugs was explored by comparing recordings with and without pharmacological stimulation. Eighteen patients in the PVS were submitted to tactile or acoustic stimulation. The latter consisted of white noise and of the voices of close relatives delivered via a digital voice recorder. Additionally, half of the patients were pharmacologically stimulated with amantadine, L-dopa or amphetamine. The effect of stimulation was assessed by recording the electroencephalogram (EEG), electromyogram (EMG), skin conductance response (SCR) and heart rate (HR). Tactile stimulation was associated with statistically significant increases in EEG and EMG parameters, SCR and HR. White noise stimulation led to significant increases in SCR and EMG parameters. The physiological responses to relatives? voices did not differ from baseline activity. Pharmacological stimulation increased the baseline level of activation, but showed no interaction with sensory stimulation. The data presented indicate that the level of arousal in patients in the PVS can be adequately monitored by measuring SCR, HR and EMG parameters.

  12. Co-occurring amphetamine use and associated medical and psychiatric comorbidity among opioid-dependent adults: results from the Clinical Trials Network

    Directory of Open Access Journals (Sweden)

    Blazer DG

    2011-07-01

    Full Text Available Daniel J Pilowsky1, Li-Tzy Wu2, Bruce Burchett2, Dan G Blazer2, George E Woody3, Walter Ling41Departments of Epidemiology and Psychiatry, Columbia University, and the New York State Psychiatric Institute, New York City, NY; 2Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University Medical Center, Durham, NC; 3Department of Psychiatry, School of Medicine, University of Pennsylvania and Treatment Research Institute, Philadelphia, PA; 4David Geffen School of Medicine, NPI/Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USABackground: In response to the rising rate of treatment admissions related to illicit use of amphetamines (eg, methamphetamine, we examined the prevalence of amphetamine use among treatment-seeking, opioid-dependent adults, explored whether amphetamine users were as likely as nonamphetamine users to enroll in opioid-dependence treatment trials, and determined whether amphetamine users manifested greater levels of medical and psychiatric comorbidity than nonusers.Methods: The sample included 1257 opioid-dependent adults screened for participation in threemultisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN001-003, which studied the effectiveness of buprenorphine for opioid detoxification under varying treatment conditions. Patients were recruited from 23 addiction treatment programs across the US. Medical and psychiatric comorbidity were examined by past-month amphetamine use (current vs former and route of administration. Five mutually exclusive groups were examined, ie, nonusers, current amphetamine injectors, current amphetamine noninjectors, former amphetamine injectors, and former amphetamine noninjectors.Results: Of the sample (n = 1257, 22.3% had a history of regular amphetamine use. Of the 280 amphetamine users, 30.3% reported injection as their primary route. Amphetamine users were more likely than nonusers to be white and use more

  13. Cardiovascular effects of 0.5 milligrams per kilogram oral d-amphetamine and possible attenuation by haloperidol.

    Science.gov (United States)

    Angrist, B; Sanfilipo, M; Wolkin, A

    2001-01-01

    In a series of earlier studies, an oral dose of 0.5 mg/kg d-amphetamine was administered to 81 patients with schizophrenia and eight normal control subjects. Seven more subjects with schizophrenia received placebo. Blood pressure and pulse rate were monitored before and 3 hours after drug administration. Blood pressure increased in both amphetamine groups, whereas placebo had no effect. However, pulse rate did not change in the schizophrenic group and only increased after 3 hours in normal control subjects as blood pressure began to decrease. Significant negative correlations between systolic blood pressure and pulse rate occurred at 2 and 3 hours, suggesting that the early cardiovascular response to amphetamine is an increase in blood pressure that recruits reflex control of heart rate. Eighteen of these subjects had hypertensive responses. Six subjects received 5 mg haloperidol intramuscularly, and 12 others had their blood pressure monitored until normalization. Haloperidol led to a more rapid decline of some but not all indices of blood pressure, suggesting that amphetamine-induced hypertension may have a dopaminergic component.

  14. Application of solid-phase microextraction combined with derivatization to the determination of amphetamines by liquid chromatography.

    Science.gov (United States)

    Cháfer-Pericás, C; Campíns-Falcó, P; Herráez-Hernández, R

    2004-10-15

    This work evaluates the utility of solid-phase microextraction (SPME) in the analysis of amphetamines by liquid chromatography (LC) after chemical derivatization of the analytes. Two approaches have been tested and compared, SPME followed by on-fiber derivatization of the extracted amphetamines, and solution derivatization followed by SPME of the derivatives formed. Both methods have been applied to measure amphetamine (AP), methamphetamine (MA), and 3,4-methylenedioxymethamphetamine (MDMA), using the fluorogenic reagent 9-fluorenylmethyl chloroformate (FMOC) and carbowax-templated resin (CW-TR)-coated fibers. Data on the application of the proposed methods for the analysis of different kind of samples are presented. When analyzing aqueous solutions of the analytes, both approaches gave similar analytical performance, but the sensitivity attainable with the solution derivatization/SPME method was better. The efficiencies observed when processing spiked urine samples by the SPME/on-fiber derivatization approach were very low. This was because the extraction of matrix components into the fiber coating prevented the extraction of the reagent. In contrast, the efficiencies obtained for spiked urine samples by the solution derivatization/SPME approach were similar to those obtained for aqueous samples. Therefore, the later method would be the method of choice for the quantification of amphetamines in urine.

  15. 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.

  16. A case story, involving the use of maltitol, a sugar alcohol, as a cutting agent in amphetamine and cocaine powders

    Directory of Open Access Journals (Sweden)

    Reitzel Lotte Ask

    2016-06-01

    Full Text Available In a criminal case involving cutting and resale of amphetamine and cocaine in the Copenhagen area of Denmark, maltitol was used as a cutting agent. The analysis of maltitol in seizures of pure diluents as well as in amphetamine and cocaine powders was carried out using reversed-phase high performance liquid chromatography (HPLC with high-resolution (HR mass spectrometric detection. Maltitol was identified in four out of nine amphetamine samples and in five out of six cocaine samples from the case in question. The use of maltitol as a cutting agent was considered by the police as a specific marker of the particular criminal group under investigation. To support or reject this hypothesis, cocaine and amphetamine samples from a four month period after the involved persons had been arrested were evaluated, also as part of the police investigation. None of these samples contained maltitol. The work described covers the part of the case involving the department of forensic chemistry, and not the whole police investigation, but everything was done within the frames given by the police. To the best of our knowledge, this is the first report of a disaccharide polyol being used as a cutting agent for illicit drugs.

  17. Effects of heavy particle irradiation and diet on amphetamine- and lithium chloride-induced taste avoidance learning in rats

    Science.gov (United States)

    Rabin, Bernard M.; Shukitt-Hale, Barbara; Szprengiel, Aleksandra; Joseph, James A.

    2002-01-01

    Rats were maintained on diets containing either 2% blueberry or strawberry extract or a control diet for 8 weeks prior to being exposed to 1.5 Gy of 56Fe particles in the Alternating Gradient Synchrotron at Brookhaven National Laboratory. Three days following irradiation, the rats were tested for the effects of irradiation on the acquisition of an amphetamine- or lithium chloride-induced (LiCl) conditioned taste avoidance (CTA). The rats maintained on the control diet failed to show the acquisition of a CTA following injection of amphetamine. In contrast, the rats maintained on antioxidant diets (strawberry or blueberry extract) continued to show the development of an amphetamine-induced CTA following exposure to 56Fe particles. Neither irradiation nor diet had an effect on the acquisition of a LiCl-induced CTA. The results are interpreted as indicating that oxidative stress following exposure to 56Fe particles may be responsible for the disruption of the dopamine-mediated amphetamine-induced CTA in rats fed control diets; and that a reduction in oxidative stress produced by the antioxidant diets functions to reinstate the dopamine-mediated CTA. The failure of either irradiation or diet to influence LiCl-induced responding suggests that oxidative stress may not be involved in CTA learning following injection of LiCl.

  18. Sensitivity and specificity to amphetamine of a French version of the 49-item form of the addiction research center inventory.

    Science.gov (United States)

    Warot, D; Danjou, P; Payan, C; Puech, A J

    1997-05-02

    The main metrological characteristics of a French version of the 49-item addiction research center inventory (ARCI) were evaluated using data collected in three controlled studies in healthy subjects. An analysis of variance showed no study effect, so the three studies were pooled. The test-retest reliability coefficients after placebo evaluated by a Spearman rank correlation test were 0.64 (P LSD (not significant). Using the same test, the test-retest reliability coefficients after amphetamine were 0.73 (P LSD (P < 0.0001). In order to assess the predictive validity of the translated questionnaire, areas under curves were calculated from the ROC diagrams for the three scores, amphetamine (A), benzedrine group (BG) and morphine benzedrine group (MBG). Two criteria validity were used: the desire to take amphetamine another time and the discrimination of the allocated treatment (amphetamine or placebo). The calculated areas under curves indicated a good capacity of prediction of the three ARCI subscales (A, BG, MBG) for both criteria.

  19. An insight into the hepatocellular death induced by amphetamines, individually and in combination: the involvement of necrosis and apoptosis.

    Science.gov (United States)

    Dias da Silva, Diana; Carmo, Helena; Lynch, Adam; Silva, Elisabete

    2013-12-01

    The liver is a vulnerable target for amphetamine toxicity, but the mechanisms involved in the drug's hepatotoxicity remain poorly understood. The purpose of the current research was to characterize the mode of death elicited by four amphetamines and to evaluate whether their combination triggered similar mechanisms in immortalized human HepG2 cells. The obtained data revealed a time- and temperature-dependent mortality of HepG2 cells exposed to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy; 1.3 mM), methamphetamine (3 mM), 4-methylthioamphetamine (0.5 mM) and D-amphetamine (1.7 mM), alone or combined (1.6 mM mixture). At physiological temperature (37 °C), 24-h exposures caused HepG2 death preferentially by apoptosis, while a rise to 40.5 °C favoured necrosis. ATP levels remained unaltered when the drugs where tested at normothermia, but incubation at 40.5 °C provoked marked ATP depletion for all treatments. Further investigations on the apoptotic mechanisms triggered by the drugs (alone or combined) showed a decline in BCL-2 and BCL- XL mRNA levels, with concurrent upregulation of BAX, BIM, PUMA and BID genes. Elevation of Bax, cleaved Bid, Puma, Bak and Bim protein levels was also seen. To the best of our knowledge, Puma, Bim and Bak have never been linked with the toxicity induced by amphetamines. Time-dependent caspase-3/-7 activation, but not mitochondrial membrane potential (∆ψm) disruption, also mediated amphetamine-induced apoptosis. The cell dismantling was confirmed by poly(ADP-ribose)polymerase proteolysis. Overall, for all evaluated parameters, no relevant differences were detected between individual amphetamines and the mixture (all tested at equieffective cytotoxic concentrations), suggesting that the mode of action of the amphetamines in combination does not deviate from the mode of action of the drugs individually, when eliciting HepG2 cell death.

  20. 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.

  1. Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors: interactions with amphetamine.

    Science.gov (United States)

    Martin-Iverson, M T; Todd, K G; Altar, C A

    1994-03-01

    To investigate behavioral and neurochemical effects of neurotrophic factors in vivo, rats received continuous 14 d infusions of either brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or vehicle unilaterally into the substantia nigra. BDNF and NT-3 decreased body weights, an effect that was sustained over the infusion period. BDNF elevated daytime and nocturnal locomotion compared with infusions of vehicle or NT-3. At 2 weeks, a systemic injection of amphetamine (1.5 mg/kg, s.c.) increased the frequencies and durations of rotations contraversive to the side of BDNF and NT-3 infusions. Both factors attenuated amphetamine-induced locomotion without affecting amphetamine-induced stereotyped behaviors such as sniffing, head movements, and snout contact with cage surfaces. Only BDNF induced backward walking, and this response was augmented by amphetamine. BDNF, but not NT-3, increased dopamine turnover in the striatum ipsilateral to the infusion relative to the contralateral striatum. Both trophic factors decreased dopamine turnover in the infused substantia nigra relative to the contralateral hemisphere and increased 5-HT turnover in the striatum of both sides. Contraversive rotations were positively correlated with dopamine content decreases and 5-HT turnover increases in the striatum ipsilateral to the infused substantia nigra. Backward walking was positively correlated with increased dopamine and 5-HT turnover in the striatum of the infused hemisphere. Supranigral infusions of BDNF and NT-3 alter circadian rhythms, spontaneous motor activity, body weights, and amphetamine-induced behaviors including locomotion and contraversive rotations. These behavioral effects of the neurotrophins are consistent with a concomitant activation of dopamine and 5-HT systems in vivo.

  2. Time-dependent effects of post-trial amphetamine treatment in rats: evidence for enhanced storage of representational memory.

    Science.gov (United States)

    Strupp, B J; Bunsey, M; Levitsky, D; Kesler, M

    1991-07-01

    Two studies were conducted to test the ability of post-trial amphetamine treatment to improve later recall in a nonaversively motivated task. These studies utilized 8- and 12-arm radial mazes, respectively, with an 11-h retention interval imposed after the rat traversed half the arms of the maze (termed, the to-be-remembered-event, or TBRE). In Experiment 1, the rats were injected with amphetamine (0, .25, and .50 mg/kg) immediately after the TBRE. Because the drug treatment improved retention, a time dependency study was conducted in which the drug (0 and .33 mg/kg) was administered 0, 3, and 6 h after the TBRE. The finding that amphetamine injection at 0, but not 3, h post-trial improved later recall indicates that the benefit derived from the former treatment is not due to proactive influences at the time of the retention test. Drug treatment 6 h post-trial produced a borderline improvement of recall; possible mechanisms are discussed. Two conclusions can be drawn from these results: (1) amphetamine administration can improve recall under conditions in which this effect cannot be attributed to alterations in information processing during either the learning or the retention sessions, indicating that the drug modulates memory storage processes; and (2) amphetamine treatment can improve working memory, thus excluding an alternative interpretation for the previous reports of impaired short-term memory in animals, all of which entailed assessments of working memory. The possibility remains, however, that the impairment seen in these tasks reflects the requirement for erasure of information from previous trials within each daily session, rather than the duration of the retention interval.

  3. Prevalence and distribution patterns of amphetamine and methamphetamine consumption in a federal state in southwestern Germany using wastewater analysis.

    Science.gov (United States)

    Meyer, Markus R; Vollerthun, Tina; Hasselbach, Ralf

    2015-11-01

    Wastewater analysis is a new approach developed to estimate drug (of abuse) consumption in large communities, such as cities or even whole countries. This paper presents data on the loads of amphetamine and methamphetamine measured in ten wastewater treatment plants in different parts of a German federal state. It provides an estimation of the intensity of the consumption and a comparison to other regions in Germany and Europe. Consumption of amphetamine and methamphetamine was estimated by analysis of drug residues in composite 24h samples of wastewater after mechanical treatment over one week by liquid chromatography-high resolution tandem mass spectrometry. Samples were collected from the inlet of ten wastewater treatment plants (WWTP) in the federal state of Saarland, representing bigger cities (>200,000 inhabitants), medium sized cities (>50,000 inhabitants), small cities (>25,000 inhabitants), and villages (<25,000 inhabitants). In each WWTP, samples were taken daily for seven consecutive days in July 2014. We observed differences of amphetamine versus methamphetamine loads (expressed as mg/day/1000 inhabitants): Amphetamine loads were much higher in all tested WWTPs indicating a low prevalence of methamphetamine abuse in the federal state of Saarland at the tested period. These findings are in line with previous reports about the distribution of amphetamine and methamphetamine in Germany and Europe. The approach confirms that wastewater analysis can provide valuable data about the abuse pattern of drugs of abuse in cities and larger areas. It can be useful for planning interventions aimed at specific areas and substances. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Granulocyte macrophage colony stimulating factor therapy for pulmonary alveolar proteinosis.

    Science.gov (United States)

    Shende, Ruchira P; Sampat, Bhavin K; Prabhudesai, Pralhad; Kulkarni, Satish

    2013-03-01

    We report a case of 58 year old female diagnosed with Pulmonary Alveolar Proteinosis (PAP) with recurrence of PAP after 5 repeated whole lung lavage, responding to subcutaneous injections of Granulocyte Macrophage Colony Stimulating Factor therapy (GM-CSF). Thus indicating that GM-CSF therapy is a promising alternative in those requiring repeated whole lung lavage

  5. Regulation of granulosa cell cocaine and amphetamine regulated transcript (CART) binding and effect of CART signaling inhibitor on granulosa cell estradiol production during dominant follicle selection in cattle.

    Science.gov (United States)

    Folger, Joseph K; Jimenez-Krassel, Fermin; Ireland, James J; Lv, Lihua; Smith, George W

    2013-12-01

    We previously established a potential role for cocaine and amphetamine regulated transcript (CARTPT) in dominant follicle selection in cattle. CARTPT expression is elevated in subordinate versus dominant follicles, and treatment with the mature form of the CARTPT peptide (CART) decreases follicle-stimulating hormone (FSH)-stimulated granulosa cell estradiol production in vitro and follicular fluid estradiol and granulosa cell CYP19A1 mRNA in vivo. However, mechanisms that regulate granulosa cell CART responsiveness are not understood. In this study, we investigated hormonal regulation of granulosa cell CART-binding sites in vitro and temporal regulation of granulosa cell CART-binding sites in bovine follicles collected at specific stages of a follicular wave. We also determined the effect of inhibition of CART receptor signaling in vivo on estradiol production in future subordinate follicles. Granulosa cell CART binding in vitro was increased by FSH, and this induction was blocked by estrogen receptor antagonist treatment. In follicles collected in vivo at specific stages of a follicular wave, granulosa cell CART binding in the F2 (second largest), future subordinate follicle increased during dominant follicle selection. Injection into the F2 follicle (at onset of diameter deviation) of an inhibitor of the o/i subclass of G proteins (previously shown to block CART actions in vitro) resulted in increased follicular fluid estradiol concentrations in vivo. Collectively, results demonstrate hormonal regulation of granulosa cell CART binding in vitro and temporal regulation of CART binding in subordinate follicles during dominant follicle selection. Results also suggest that CART signaling may help suppress estradiol-producing capacity of the F2 (subordinate) follicle during this time period.

  6. Analysis of repeated measures data

    CERN Document Server

    Islam, M Ataharul

    2017-01-01

    This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

  7. Hallucinogens causing seizures? A case report of the synthetic amphetamine 2,5-dimethoxy-4-chloroamphetamine.

    Science.gov (United States)

    Burish, Mark J; Thoren, Katie L; Madou, Maura; Toossi, Shahed; Shah, Maulik

    2015-01-01

    Although traditional hallucinogenic drugs such as marijuana and lysergic acid diethylamide (LSD) are not typically associated with seizures, newer synthetic hallucinogenic drugs can provoke seizures. Here, we report the unexpected consequences of taking a street-bought hallucinogenic drug thought to be LSD. Our patient presented with hallucinations and agitation progressing to status epilepticus with a urine toxicology screen positive only for cannabinoids and opioids. Using liquid chromatography high-resolution mass spectrometry, an additional drug was found: an amphetamine-derived phenylethylamine called 2,5-dimethoxy-4-chloroamphetamine. We bring this to the attention of the neurologic community as there are a growing number of hallucinogenic street drugs that are negative on standard urine toxicology and cause effects that are unexpected for both the patient and the neurologist, including seizures.

  8. Chiral analysis of amphetamines, methadone and metabolites in biological samples by electrodriven methods.

    Science.gov (United States)

    Mandrioli, Roberto; Mercolini, Laura; Raggi, Maria A

    2011-10-01

    Amphetamines and methadone are synthetic chiral drugs with a high potential for abuse. As such, several analytical methods have been developed for their enantioseparation and analysis in biological tissues, and some of these are based on electrodriven techniques. In this review, the most important and recent of these latter methods are reviewed and their main advantages and disadvantages are discussed. Particular attention is paid to the suitability of each method for the application to the biological matrix of interest: while all methods have been successfully applied for one or more biological tissues, to reach this goal they must overcome the sensitivity problem that is common to almost all capillary electrophoretic techniques. Most methods use one or more cyclodextrin derivatives as the chiral selector, thus the separation mechanism is not particularly complicated or unusual.

  9. Simultaneous determination of amphetamines and ketamines in urine by gas chromatography/mass spectrometry.

    Science.gov (United States)

    Lin, Huei Ru; Lua, Ahai Chang

    2006-01-01

    A method for the simultaneous determination of amphetamines and ketamines (ketamine, norketamine and dehydronorketamine) in urine samples by gas chromatography/mass spectrometry was developed and validated. Urine samples were extracted with organic solvent and derivatized with trifluoroacetic anhydride (TFAA). The limits of detection and limits of quantification for each analyte were lower than 19 and 30 ng/mL, respectively. Within-day and between-day precisions were within 0.5% and 10.6%, respectively. Biases for three levels of control samples were within -10.6% and +7.8%. The concentration of dehydronorketamine was greater than those of ketamine or norketamine in 19 of 35 ketamine-positive samples. A group of 110 human urine samples previously determined to contain at least one of the target analytes was analyzed using the new method, and excellent agreement was observed with previous results.

  10. Capillary gas-liquid chromatography separation of phenethylamines in amphetamine-positive urine samples.

    Science.gov (United States)

    DePace, A; Verebey, K; elSohly, M

    1990-11-01

    Good gas chromatography (GC) separation of molecules is essential for clean gas chromatography/mass spectrometry (GC/MS) confirmation of compounds. The trifluoro derivatives of ephedrine (E) and methamphetamine (MA) coelute on dimethyl silicone capillary columns, such as DB-1, which are most commonly used by chromatographers. Methods are described to separate E and MA to aid GC/MS confirmations of methamphetamine, ephedrine, or both E and MA together, whichever may be present in Enzyme Immunoassay (EIA)-analyzed amphetamine-positive urine samples. The use of the heptafluoro derivatives of E and MA on a DB-1 column, or the trifluoro derivatives of E and MA on a DB-17 column, is suggested for good gas chromatographic separation.

  11. Effects of d-amphetamine and smoking abstinence on cue-induced cigarette craving.

    Science.gov (United States)

    Alsene, Karen M; Mahler, Stephen V; de Wit, Harriet

    2005-08-01

    In this study, the authors investigated the effects of the indirect dopamine agonist d-amphetamine (AMPH) on cue-induced cigarette craving in smokers. Abstinent or nonabstinent cigarette smokers (N=21) rated their cravings for cigarettes and for food (control) after pretreatment with AMPH (15 mg) or placebo and before and after viewing blocks of smoking-related, food-related, and neutral pictures. Before the cues were presented, AMPH increased cigarette craving and decreased food craving. Smoking and food cues increased craving for cigarettes and for food, respectively. AMPH also further increased cigarette craving (and decreased food craving) after cue presentation, but it did so regardless of cue type (food or smoking). Smoking abstinence markedly increased craving regardless of cue presentation or drug condition. These results suggest that both AMPH and smoking abstinence can increase cigarette craving, but they do not appear to specifically affect responses to conditioned smoking-related cues. ((c) 2005 APA, all rights reserved).

  12. COCAINE AMPHETAMINE REGULATED TRANSCRIPT%可卡因-苯丙胺调节转录肽

    Institute of Scientific and Technical Information of China (English)

    艾恒; 莫书荣; 路长林; 黄矛; 由振东

    2006-01-01

    可卡因-苯丙胺调节转录肽(cocaine amphetamine regulatedtranscript,CART肽)是一种在体内分布广泛的神经肽类物质.它具有广泛的生理作用,在奖赏与强化、进食与肥胖、精神焦虑行为、体液平衡、免疫功能、新陈代谢、内分泌以及其他的一些生理过程中均有作用.尤其CART肽在药物依赖中的作用研究使其自1981年发现以来迅速成为神经肽方面研究热点.

  13. LC-MS/MS screening method for designer amphetamines, tryptamines, and piperazines in serum.

    Science.gov (United States)

    Wohlfarth, Ariane; Weinmann, Wolfgang; Dresen, Sebastian

    2010-04-01

    Since the late 1990s and early 2000s, derivatives of well-known designer drugs as well as new psychoactive compounds have been sold on the illicit drug market and have led to intoxications and fatalities. The LC-MS/MS screening method presented covers 31 new designer drugs as well as cathinone, methcathinone, phencyclidine, and ketamine which were included to complete the screening spectrum. All but the last two are modified molecular structures of amphetamine, tryptamine, or piperazine. Among the amphetamine derivatives are cathinone, methcathinone, 3,4-DMA, 2,5-DMA, DOB, DOET, DOM, ethylamphetamine, MDDMA, 4-MTA, PMA, PMMA, 3,4,5-TMA, TMA-6 and members of the 2C group: 2C-B, 2C-D, 2C-H, 2C-I, 2C-P, 2C-T-2, 2C-T-4, and 2C-T-7. AMT, DPT, DiPT, MiPT, DMT, and 5MeO-DMT are contained in the tryptamine group, BZP, MDBP, TFMPP, mCPP, and MeOPP in the piperazine group. Using an Applied Biosystems LC-MS/MS API 365 TurboIonSpray it is possible to identify all 35 substances. After addition of internal standards and mixed-mode solid-phase extraction the analytes are separated using a Synergi Polar RP column and gradient elution with 1 mM ammonium formate and methanol/0.1% formic acid as mobile phases A and B. Data acquisition is performed in MRM mode with positive electro spray ionization. The assay is selective for all tested substances. Limits of detection were determined by analyzing S/N-ratios and are between 1.0 and 5.0 ng/mL. Matrix effects lie between 65% and 118%, extraction efficiencies range from 72% to 90%.

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

    Science.gov (United States)

    Jakobsson, Gerd; Kronstrand, Robert

    2014-06-01

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

  15. The Histaminergic Tuberomamillary Nucleus Is Involved in Appetite for Sex, Water and Amphetamine.

    Directory of Open Access Journals (Sweden)

    Marco Contreras

    Full Text Available The histaminergic system is one component of the ascending arousal system which is involved in wakefulness, neuroendocrine control, cognition, psychiatric disorders and motivation. During the appetitive phase of motivated behaviors the arousal state rises to an optimal level, thus giving proper intensity to the behavior. Previous studies have demonstrated that the histaminergic neurons show an earlier activation during the appetitive phase of feeding, compared to other ascending arousal system nuclei, paralleled with a high increase in arousal state. Lesions restricted to the histaminergic neurons in rats reduced their motivation to get food even after 24 h of food deprivation, compared with intact or sham lesioned rats. Taken together, these findings indicate that the histaminergic system is important for appetitive behavior related to feeding. However, its role in other goal-directed behaviors remains unexplored. In the present work, male rats rendered motivated to obtain water, sex, or amphetamine showed an increase in Fos-ir of histaminergic neurons in appetitive behaviors directed to get those reinforcers. However, during appetitive tests to obtain sex, or drug in amphetamine-conditioned rats, Fos expression increased in most other ascending arousal system nuclei, including the orexin neurons in the lateral hypothalamus, dorsal raphe, locus coeruleus and laterodorsal tegmental neurons, but not in the ventral tegmental area, which showed no Fos-ir increase in any of the 3 conditions. Importantly, all these appetitive behaviors were drastically reduced after histaminergic cell-specific lesion, suggesting a critical contribution of histamine on the intensity component of several appetitive behaviors.

  16. Dopamine stimulation via infusion in the lateral ventricle.

    Science.gov (United States)

    Biagioni, Francesca; Busceti, Carla L; Molinaro, Gemma; Battaglia, Giuseppe; Giorgi, Filippo S; Ruggieri, Stefano; Fornai, Francesco

    2006-08-01

    Continuous dopamine (DA) stimulation is a therapeutic approach that applies to the treatment of motor fluctuations due to pulsatile DA stimulation in Parkinson's disease (PD), to cure the abuse of drugs, such as cocaine or amphetamine (which produce short-lasting peaks of extracellular DA), and as a safe therapeutic approach to avoid hedonistic homeostatic dysregulation (which sometime develops as an abuse pattern in PD patients receiving a pulsatile DA replacement therapy). However, systemic continuous delivery of DA agonists leads to a variety of side effects. In search for an alterative approach, in the present study we evaluated the possibility of delivering intracerebroventricularly (i.c.v.), a DA agonist: lisuride that was already shown to be effective when administered continuously subcutaneously (s.c.). In particular, we were interested in examining whether lisuride infused within the lateral ventricle was still able to stimulate DA receptor by inducing contralateral turning behavior in hemiparkinsonian rats. We found that lisuride, when infused in the lateral ventricle was effective in reducing the threshold for stimulating DA receptors. These results offer a more reliable and safe therapeutic approach to deliver continuous DA selectively in the brain.

  17. Effects of d-amphetamine on short- and long-term memory in spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley rats.

    Science.gov (United States)

    Meneses, A; Ponce-Lopez, T; Tellez, R; Gonzalez, R; Castillo, C; Gasbarri, A

    2011-01-01

    Diverse studies indicate that the attention deficit hyperactivity disorder (ADHD) is associated with alterations in encoding processes, including working or short-term memory. Some ADHD dysfunctional domains are reflected in the spontaneously hypertensive rat (SHR). Here SHR-saline group showed significantly poor STM and LTM relative to SD and WKY saline rats. SD and WKY rats treated with d-amphetamine displayed better STM and LTM, compared to SD-vehicle, WKY-vehicle or SHR-d-amphetamine groups.

  18. Amphetamine and N-acetylamphetamine incorporation into hair: an investigation of the potential role of drug basicity in hair color bias.

    Science.gov (United States)

    Borges, C R; Wilkins, D G; Rollins, D E

    2001-01-01

    To elucidate the role of drug basicity in the preferential incorporation of certain drugs into dark hair rather than light hair, Long-Evans rats were dosed with amphetamine or its non-basic analogue N-acetylamphetamine (N-AcAp) and their hair evaluated for drug content. Rats were shaved prior to dosing. On the 14th day after dosing, hair from the same area that was shaved prior to dosing was shaved and collected. After the addition of amphetamine-d3 or N-AcAp-d3 as an internal standard, hair samples (20 mg) were digested in 1M NaOH at 37 degrees C. Digested solutions were then extracted with n-butyl chloride/chloroform (4:1, v/v). After drying and reconstituting, samples were injected onto a ThermoQuest TSQ liquid chromatography-tandem mass spectrometry instrument for analysis. Black hair from rats dosed with amphetamine (n = 8) was found to contain 6.44 +/- 1.31 (SD) ng amphetamine/mg hair. White hair from the same rats contained 2.04 +/- 0.58 ng amphetamine/mg hair. In contrast, no difference in N-AcAp content was found between black hair (0.87 +/- 0.08 ng N-AcAp/mg hair) and white hair (0.83 +/- 0.15 ng N-AcAp/mg hair) from rats dosed with N-AcAp (n = 8).

  19. Vagus Nerve Stimulation

    Science.gov (United States)

    Vagus nerve stimulation Overview By Mayo Clinic Staff Vagus nerve stimulation is a procedure that involves implantation of a device that stimulates the vagus nerve with electrical impulses. There's one vagus nerve on ...

  20. Development and validation of two LC-MS/MS methods for the detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine using turbulent flow chromatography.

    Science.gov (United States)

    Schaefer, Nadine; Peters, Benjamin; Schmidt, Peter; Ewald, Andreas H

    2013-01-01

    In the context of driving ability diagnostics in Germany, administrative cutoffs for various drugs and pharmaceuticals in urine have been established. Two liquid chromatography-tandem mass spectrometry methods for simultaneous detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine were developed and validated. A 500-μL aliquot of urine was diluted and fortified with an internal standard solution. After enzymatic cleavage, online extraction was performed by an ion-exchange/reversed-phase turbulent flow column. Separation was achieved by using a reversed-phase column and gradient elution. For detection, a Thermo Fisher TSQ Quantum Ultra Accurate Mass tandem mass spectrometer with positive electrospray ionization was used, and the analytes were measured in multiple-reaction monitoring mode detecting two transitions per precursor ion. The total run time for both methods was about 15 min. Validation was performed according to the guidelines of the Society of Toxicological and Forensic Chemistry. The results of matrix effect determination were between 78% and 116%. The limits of detection and quantification for all drugs, except zopiclone, were less than 10 ng/mL and less than 25 ng/mL, respectively. Calibration curves ranged from 25 to 200 ng/mL for amphetamines, designer amphetamines, and benzoylecgonine, from 25 to 250 ng/mL for benzodiazepines, from 12.5 to 100 ng/mL for morphine, codeine, and dihydrocodeine, and from 5 to 50 ng/mL for buprenorphine and norbuprenorphine. Intraday and interday precision values were lower than 15%, and bias values within ± 15% were achieved. Turbulent flow chromatography needs no laborious sample preparation, so the workup is less time-consuming compared with gas chromatography-mass spectrometry methods. The methods are suitable for quantification of multiple analytes at the cutoff concentrations required for driving ability diagnostics in Germany.

  1. Limitations on quantum key repeaters.

    Science.gov (United States)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  2. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    Energy Technology Data Exchange (ETDEWEB)

    Provenzano, Virgil [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Della Torre, Edward; Bennett, Lawrence H. [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States); ElBidweihy, Hatem, E-mail: Hatem@gwmail.gwu.edu [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States)

    2014-02-15

    The Gd{sub 5}Ge{sub 2}Si{sub 2} alloy and the off-stoichiometric Ni{sub 50}Mn{sub 35}In{sub 15} Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd{sub 5}Ge{sub 2}Si{sub 2} and Ni{sub 50}Mn{sub 35}In{sub 15} alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

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

    Science.gov (United States)

    Zaimov, K; Kokoshkarova, A

    1978-10-01

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

  4. Measurement uncertainty for the determination of amphetamines in urine by liquid-phase microextraction and gas chromatography-mass spectrometry.

    Science.gov (United States)

    Franco de Oliveira, Sarah Carobini Werner de Souza Eller; Yonamine, Mauricio

    2016-08-01

    A gas chromatography-mass spectrometry method for the determination of amphetamines in urine samples by means of liquid-phase microextraction was validated, including calculation of measurement uncertainty. After extraction in the three-phase mode, acceptor phase was withdrawn from the fiber and the residue was derivatized with trifluoroacetic anhydride. The method showed to be very simple, rapid and it required a significantly low amount of organic solvent for extraction. The limits of detection were 10 and 20μg/L for amphetamine and methamphetamine, respectively. The calibration curves were linear over the specified range (20μg/L to 1400μg/L; r(2)>0.99). The method showed to be both precise and accurate and a relative combined uncertainty of 2% was calculated. In order of importance, the factors which were more determinant for the calculation of method uncertainty were: analyte concentration, sample volume, trueness and method precision.

  5. Performance characteristics of DRI, CEDIA, and REMEDi systems for preliminary tests of amphetamines and opiates in human urine.

    Science.gov (United States)

    Huang, Min-Kun; Dai, Yu-Shan; Lee, Choung-Huei; Liu, Chiareiy; Tsay, Wen-Ing; Li, Jih-Heng

    2006-01-01

    Arrestee urine specimens (930) were tested with DRI, CEDIA, and REMEDi; those that tested positive for amphetamines and opiates (616 and 414, respectively) were then confirmed by gas chromatography-mass spectrometry. The performance characteristics of these three preliminary systems were evaluated using the following commonly used parameters: true positive, true negative, false positive, and false negative. The sensitivity, specificity, and efficiency of these methods were also calculated. Data derived from this study indicated DRI and CEDIA adapted by this study generated acceptable preliminary test results for amphetamine/methamphetamine and morphine/codeine, but not for MDA/MDMA and REMEDi has lower sensitivity than DRI and CEDIA, but with better specificity and efficiency, supporting its use under emergency room settings where drug concentrations in overdose cases are expectedly at high levels.

  6. Stimulant mechanisms of cathinones - effects of mephedrone and other cathinones on basal and electrically evoked dopamine efflux in rat accumbens brain slices.

    Science.gov (United States)

    Opacka-Juffry, Jolanta; Pinnell, Thomas; Patel, Nisha; Bevan, Melissa; Meintel, Meghan; Davidson, Colin

    2014-10-01

    Mephedrone, an erstwhile "legal high", and some non-abused cathinones (ethcathinone, diethylpropion and bupropion) were tested for stimulant effects in vitro, through assessing their abilities to increase basal and electrically evoked dopamine efflux in rat accumbens brain slices, and compared with cocaine and amphetamine. We also tested mephedrone against cocaine in a dopamine transporter binding study. Dopamine efflux was electrically evoked and recorded using voltammetry in the rat accumbens core. We constructed concentration response curves for these cathinones for effects on basal dopamine levels; peak efflux after local electrical stimulation and the time-constant of the dopamine decay phase, an index of dopamine reuptake. We also examined competition between mephedrone or cocaine and [(125)I]RTI121 at the dopamine transporter. Mephedrone was less potent than cocaine at displacing [(125)I]RTI121. Mephedrone and amphetamine increased basal levels of dopamine in the absence of electrical stimulation. Cocaine, bupropion, diethylpropion and ethcathinone all increased the peak dopamine efflux after electrical stimulation and slowed dopamine reuptake. Cocaine was more potent than bupropion and ethcathinone, while diethylpropion was least potent. Notably, cocaine had the fastest onset of action. These data suggest that, with respect to dopamine efflux, mephedrone is more similar to amphetamine than cocaine. These findings also show that cocaine was more potent than bupropion and ethcathinone while diethylpropion was least potent. Mephedrone's binding to the dopamine transporter is consistent with stimulant effects but its potency was lower than that of cocaine. These findings confirm and further characterize stimulant properties of mephedrone and other cathinones in adolescent rat brain.

  7. On-line derivatization gas chromatography with furan chemical ionization tandem mass spectrometry for screening of amphetamines in urine.

    Science.gov (United States)

    Tzing, Shin-Hwa; Ghule, Anil; Liu, Jen-Yu; Ling, Yong-Chien

    2006-12-22

    A simple alternative method with minimal sample pretreatment is investigated for screening of amphetamines in small volume (using only 20 microL) of urine sample. The method is sensitive and selective. The method uses gas chromatography (GC) direct sample introduction (DSI) for on-line derivatization (acylation) of amphetamines to improve sensitivity. Furan as chemical ionization (CI) reagent in conjunction with tandem mass spectrometry (MS/MS) is used to improve selectivity. Low background with sharp protonated molecular ion peaks of analytes is the evidence of improvement in sensitivity and selectivity. Blank urine samples spiked with known amounts of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine and 3,4-methylenedioxyethylamphetamine is analyzed. Selected ion monitoring of the characteristic product ions (m/z 119+136+150+163) using furan CI-MS/MS in positive ion mode is used for quantification. Limits of detection (LOD) between 0.4 and 1.0 ng mL(-1) and limits of quantitation (LOQ) between 1.0 and 2.0 ng mL(-1) are established. Linear response over the range of 1-1000 ng mL(-1) (r(2)>0.997) is observed for all analytes, except for methamphetamine (2.0-1000 ng mL(-1)). Good accuracy between 86 and 113% and precision ranging from 4 to 18% is obtained. The method is also tested on real samples of urine from suspected drug abusers. This method could be used for screening and determination of amphetamines in urine samples, however needs additional work for full validation.

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

    Science.gov (United States)

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

    2017-09-04

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

  9. Cocaine and amphetamine elicit differential effects in rats with a unilateral injection of dopamine transporter antisense oligodeoxynucleotides.

    Science.gov (United States)

    Silvia, C P; Jaber, M; King, G R; Ellinwood, E H; Caron, M G

    1997-02-01

    We have developed an antisense oligodeoxynucleotide to the dopamine transporter and used it to discriminate the behavioral properties of amphetamine and cocaine. In SK-N-MC cells permanently transfected with the dopamine transporter complementary DNA, treatment with 5 mM antisense oligodeoxynucleotide reduced dopamine uptake by 25% when compared to sense control. Unilateral intranigral administration of dopamine transporter antisense (50 microM) twice daily in freely moving rats for 2.5 days was sufficient to reduce dopamine transporter messenger RNA by 70% as measured by in situ hybridization, but not protein levels as measured by [3H]mazindol binding. However, intranigral treatment via implanted osmotic minipump over a period of seven days produced reductions in both dopamine transporter messenger RNA and protein levels (32%) at a dose of 500 pmol/day. These results indicate a longer half-life for the dopamine transporter than expected. Potassium chloride depolarization of ipsilateral striatal slices showed a greater than 200% increase in dopamine overflow on the antisense-treated side compared to the control side. Since imbalance of dopamine tone is known to induce rotational activity, we tested this behavioral paradigm in rats treated with various oligodeoxynucleotides at different doses and time-points. We have found that antisense-treated animals did not rotate spontaneously under any experimental conditions. Using various psychostimulants that target the dopamine transporter and increase dopamine levels, we found that the antisense-treated animals consistently rotated contralaterally in response to amphetamine (2 mg/kg), but not to cocaine (10 mg/kg) or nomifensine (10 mg/kg). These results bring in vivo evidence for a different mode of action of amphetamine and cocaine on the dopamine transporter and lend direct support to the view that amphetamine acts as a dopamine releaser, whereas cocaine acts by blocking dopamine transport.

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

    OpenAIRE

    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...

  11. Negative visuospatial priming in isolation-reared rats: Evidence of resistance to the disruptive effects of amphetamine.

    Science.gov (United States)

    Amitai, Nurith; Powell, Susan; Weber, Martin; Swerdlow, Neal R; Young, Jared W

    2015-12-01

    Negative visuospatial priming (NP) represents a quantifiable measure of inhibitory information processing that is disrupted in several neurodevelopmental and psychiatric disorders, including schizophrenia. We developed a novel rodent NP task to investigate mechanisms underlying NP and its role in various disorders, and to test potential therapeutics. In the present studies, we further characterized this novel paradigm by investigating whether NP is disrupted in rats reared in isolation, a developmental manipulation that produces a range of abnormalities in behavior, neurochemistry, and brain structure that mirror aspects of schizophrenia pathology. We also further explored the role of monoaminergic signaling in NP and the effects of isolation rearing by challenging both socially reared and isolation-reared rats with D-amphetamine during the NP task. Although fewer isolation-reared animals learned the complex NP task, those that learned exhibited unaffected NP compared with socially reared rats. Consistent with previous reports, D-amphetamine impaired NP and increased motor impulsivity in socially reared rats. In contrast, D-amphetamine did not affect NP or motor impulsivity in isolation-reared rats. These data confirm a monoaminergic influence on NP behavior and indicate that rats reared in isolation have altered dopaminergic sensitivity.

  12. Simultaneous determination of HFBA-derivatized amphetamines and ketamines in urine by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Lee, Hei Hwa; Lee, Jong Feng; Lin, Sin Yu; Chen, Ping Ho; Chen, Bai Hsiun

    2011-04-01

    To facilitate the analysis of targeted drugs under high sample volume testing environment, an extraction, derivatization and gas chromatographic-mass spectrometric analysis method was developed for simultaneously determination of amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), ketamine, and norketamine in urine. This method utilized solid-phase extraction in conjunction with derivatization using heptafluorobutyric anhydride (HFBA) as the derivatization reagent. Using a 1-mL sample, the limits of quantitation achieved for the analysis of AMP, MAMP, MDA, MDMA, MDEA, ketamine, and norketamine were 25, 15, 60, 60, 70, 25, and 30 ng/mL, respectively. Upper limits of quantitation were 8000 ng/mL for all amphetamines and 6000 ng/mL for ketamine and norketamine. Except for dehydronorketamine (DHNK), within-day and between-day precisions (as expressed in CV%) for quality control samples were ≤ 3.1% and ≤ 4.95%, respectively. Except DHNK, the within-day accuracy ranged between 96.0% and 110.7% and the between-day accuracy ranged between 96.9% and 108.7%. A group of 107 urine samples previously determined to contain the target analytes were analyzed by this new approach. Quantitative data produced by both methods agreed well. With this new approach, we were able to use a single analytical protocol to conduct the confirmation test for samples that preliminarily tested positive (by immunoassay) for amphetamines, ketamine, or both.

  13. Rapid screening method for determination of Ecstasy and amphetamines in urine samples using gas chromatography-chemical ionisation mass spectrometry.

    Science.gov (United States)

    Pellegrini, M; Rosati, F; Pacifici, R; Zuccaro, R; Romolo, F S; Lopez, A

    2002-04-05

    The need for analytical screening tests more reliable and valid to detect amphetamine and related "designer drugs" in biological samples is becoming critical, due to the increasing diffusion of these drugs on the European illegal market. The most common screening procedures based on immunoassays suffer a number of limitations, including low sensitivity, lack of specificity and limited number of detectable substances. This paper describes a screening method based on gas-chromatography-mass-spectrometry (GC/MS) using positive chemical ionisation (PCI) detection. Methanol was used as reactant gas in the ionisation chamber. Molecular ions of different compounds were monitored, allowing a sensitivity of 5-10 ng/ml with high selectivity. The sensitivity of the method gives positive results in samples taken 48-72 h after intake of one dose of 50-100 mg. The method is simple and rapid. Sample preparation was limited to one liquid-liquid extraction, without any hydrolysis and derivatisation. Hydrolysis is critical to identify metabolites excreted as conjugates. Blank urine samples spiked with known amounts of amphetamine (AM), methylamphetamine (MA), methylenedioxyamphetamine (MDA), methylenedioxymethylamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA) and methylenedioxyphenyl-N-methyl-2-butanamine (MBDB) were analysed. The method was successfully tested on real samples of urine from people, whose use of amphetamine was suspected, and results were compared with results obtained with immunoassays.

  14. Reduced palatability in lithium- and activity-based, but not in amphetamine-based, taste aversion learning.

    Science.gov (United States)

    Dwyer, Dominic M; Boakes, Robert A; Hayward, Andrew J

    2008-10-01

    Conditioned taste aversions (CTA) based on lithium chloride (Experiment 1), amphetamine (Experiment 2), and wheel running (Experiment 3) were examined using the analysis of the microstructure of licking to measure the palatability of the taste serving as the conditioned stimulus (CS). Pairing saccharin with amphetamine reduced saccharin intake without reducing the size of licking clusters, initial lick rate, or the distribution of inter-lick intervals (ILIs) within a cluster. By contrast, pairing saccharin with lithium or wheel-running reduced saccharin intake as well as lick cluster size, initial lick rate, and the distribution of ILIs within a cluster. As lick cluster size, initial lick rate, and ILI distribution can be used as indices of stimulus palatability, the current results indicate that taste aversions based on either lithium or activity reduced the palatability of the CS. This suggests that aversions based on both lithium and wheel running involve conditioned nausea to the CS taste. The absence of similar changes in licking microstructure with amphetamine-based CTA is consistent with other evidence indicating this does not involve nausea.

  15. Simultaneous quantification of amphetamine, opiates, ketamine and relative metabolites in urine for confirmatory analysis by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Lin, Huei-Ru; Choi, Ka-Ian; Lin, Tzu-Chieh; Hu, Anren

    2013-06-15

    The rise in amphetamine, ketamine and opiates abuse in Taiwan has created a need for a reliable confirmatory assay. A method that combines superficially porous liquid chromatography tandem mass spectrometry (LC-MS/MS) with solid-phase extraction (SPE) was developed for the simultaneous quantification of amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), ketamine, opiates, and their corresponding metabolites in urine. The total run time of the method was 6.7min including equilibration time. The method was validated in accordance with the European Commission (EC) Decision 2002/642/EC. The within- and between-day precision was below 13.6% and the accuracy ranged from -17.1% to +9.9% for all analytes. Ion suppression was observed but compensated by using deuterated internal standards. No carryover was detected and the analytes were stable at room temperature for 16h, and for 72h at 4°C, and three-thaw cycles. The method was further validated by comparison with a reference gas chromatography-mass spectrometry (GC-MS) method, using 52 authentic urine samples. The results indicated that for the target analytes studied, the LC-MS/MS analysis was as precise, accurate, and specific as the GC-MS method. In conclusion, the present LC-MS/MS method is robust and reliable, and suitable for use as a confirmation assay in the simultaneous urine drug testing and quantification of amphetamines, ketamines, and opiates.

  16. Evaluation of commercial multi-drug oral fluid devices to identify 39 new amphetamine-designer drugs.

    Science.gov (United States)

    Nieddu, Maria; Burrai, Lucia; Trignano, Claudia; Boatto, Gianpiero

    2014-03-01

    Recently, the diffusion on the black market of new psychoactive substances not controlled and often sold as 'legal highs', is exponentially increasing in Europe. Generally, the first analysis for these drugs involves an immunoassay screening in urine or plasma. Actually, there is growing interest in the use of oral fluid (OF) as alternative specimen over conventional biological fluids for drug testing, because of the significant advantages, as a non-invasive collection under direct observation without undue embarrassment or invasion of privacy, and a good correlation with plasma analytical data. Few assays have been developed for detection of new psychoactive compounds in biological samples, so it is important to investigate how they may or may not react in pre-existing commercial immunoassays. In this paper, two different multi-drugs oral fluid screen devices (OFDs) (Screen® Multi-Drug OFD and GIMA One Step Multi-Line Screen Test OFD) were evaluated to determine the cross-reactivity of thirty-nine new amphetamine designer drugs, including twelve substances officially recognized as illicit by italian legislation. Cross-reactivity towards most drugs analyzed was <1 in assays targeting amphetamine (AMP) or methamphetamine (MET). Only two (p-methoxyamphetamine and p-methoxymethamphetamine) of all tested amphetamines gave a positive result.

  17. EAMJ Dec. Repeatability.indd

    African Journals Online (AJOL)

    2008-12-12

    Dec 12, 2008 ... Results:Kappa values for four-week repeatability for the wheeze and asthma questions were 0.61 ... for logistic, cultural and ethical reasons, to use ... individual with baseline forced expiratory volume in .... period is likely to also include the effects of true ... data, the writing of the manuscript or the decision.

  18. Comparison and evaluation of DRI methamphetamine, DRI ecstasy, Abuscreen ONLINE amphetamine, and a modified Abuscreen ONLINE amphetamine screening immunoassays for the detection of amphetamine (AMP), methamphetamine (MTH), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA) in human urine.

    Science.gov (United States)

    Stout, Peter R; Klette, Kevin L; Wiegand, Russell

    2003-01-01

    The performances of four immunoassays (DRI amphetamines, DRI ecstasy, Abuscreen ONLINE amphetamines, and a modified Abuscreen ONLINE amphetamines) were evaluated for control failure rates, sensitivity, and specificity for amphetamine (AMP), methamphetamine (MTH), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA). The two DRI reagents and the ONLINE reagents were run according to manufacturer specifications using a Roche Hitachi Modular DDP system. The modified ONLINE reagent was calibrated with MDMA and had 16mM sodium periodate added to the R2 reagent. These assays were run on approximately 27,500 human urine samples and 7000 control urine samples prepared at 350 and 674 ng/mL over the course of 8 days. All assays were calibrated using a single point, qualitative cutoff standard with the manufacturer-recommended compound at the Department of Defense cutoff (500 ng/mL). Gas chromatography-mass spectrometry (GC-MS) confirmation was conducted on screened-positive samples. Control performance for the manufacturer recommended assays was excellent, with a maximum qualitative control failure rate of 2.03%. The modified ONLINE reagent demonstrated poor control performance with a maximum failure rate of 38.3% and showed no improved MDMA sensitivity when compared with the ONLINE reagent; the confirmation rate (20%) was improved when compared with the production ONLINE reagent (8