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Sample records for alcohol amphetamines barbiturates

  1. 4 CFR 25.8 - Alcoholic beverages and narcotics.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited..., marijuana, barbiturate, or amphetamine. This prohibition shall not apply in cases where the drug is...

  2. 4 CFR 25.8 - Alcoholic beverages and narcotics.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited..., marijuana, barbiturate, or amphetamine. This prohibition shall not apply in cases where the drug is...

  3. 4 CFR 25.8 - Alcoholic beverages and narcotics.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited..., marijuana, barbiturate, or amphetamine. This prohibition shall not apply in cases where the drug is...

  4. 4 CFR 25.8 - Alcoholic beverages and narcotics.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited..., marijuana, barbiturate, or amphetamine. This prohibition shall not apply in cases where the drug is...

  5. 4 CFR 25.8 - Alcoholic beverages and narcotics.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited..., marijuana, barbiturate, or amphetamine. This prohibition shall not apply in cases where the drug is...

  6. Amphetamines

    MedlinePlus

    ... in the powder before eating it). Many study drugs are amphetamines. Short-Term Effects When amphetamines get into the body, they go to work on the central nervous system. Amphetamines affect a brain chemical called dopamine, increasing it so the user ...

  7. A comparative analysis of the effects of narcotics, alcohol and the barbiturates on the hypothalamic-pituitary-gonadal axis.

    PubMed

    Cicero, T J; Badger, T M

    1977-01-01

    The purpose of this paper is to provide an overview of our current state of knowledge regarding the effects of alcohol, the narcotics and the barbiturates on the hypothalamic-pituitary-gonadal axis in the male. Three facets of this problem will be considered: acute drug effects; chronic effects, particularly with respect to the development of tolerance and physical dependence; and, finally, an attempt will be made to indicate the way in which these three substances of abuse are similar and/or dissimilar in their effects on this system. The effects of acute and chronic treatment with narcotics, alcohol and the barbiturates will be discussed first and then an attempt will be made, in a General Discussion, to summarize the data, make general comparisons between the drugs and suggest future lines of research.

  8. Barbiturate Intoxication

    PubMed Central

    Goodman, Jay M.; Bischel, Margaret D.; Wagers, Park W.; Barbour, Benjamin H.

    1976-01-01

    The complications encountered in caring for 185 patients intoxicated with barbiturates were reviewed. The population consisted of 142 patients with long-acting barbiturate concentrations of 8 mg per 100 ml or greater, 20 patients with short-acting barbiturate concentrations of 3 mg per 100 ml or greater and 23 consecutive patients with short-acting barbiturate intoxication referred for monitoring. Pneumonia was the major cause of morbidity and mortality and correlated best with the initial depth of coma and the use of an endotracheal tube in treatment. Cardiovascular instability manifested by pulmonary edema was the next leading cause of morbidity and mortality and correlated best with the initial depth of coma and the quantity of intravenous fluid administered. In retrospect, use of eliminative measures such as dialysis would probably not have altered the outcome in most of the patients who died and attempts at forced diuresis may have contributed to several deaths. Particular emphasis should be placed on the problems of sepsis and fluid therapy in the management of these patients. PMID:1258466

  9. [On the history of barbiturates].

    PubMed

    Norn, Svend; Permin, Henrik; Kruse, Edith; Kruse, Poul R

    2015-01-01

    Throughout the history of humanity, numerous therapeutic agents have been employed for their sedative and hypnotic properties such as opium, henbane (Hyoscyamus niger) and deadly nightshade (Atropa belladonna), but also alcohol and wine. In the 19th century potassium bromide was introduced as a sedative - and antiepileptic drug and chloral hydrate as sedative-hypnotics. A new era was reached by the introduction of barbiturates. The story started with the chemist Adolf von Baeyer. His breakthrough in the synthesis of new agents as barbituric acid and indigo and his education of young chemists was of great importance for the science of organic chemistry and the development of the dye and medicine industry in the late 19th century. The next important step was the development of barbiturates. The pioneers were Josef von Mering and Emil Fischer. Using the Grimaux-method they synthesized various barbiturates. It was von Mering who got the idea of introducing ethyl groups in the inactive barbituric acid to obtain sedatives, but the synthesis was succeeded by the chemist Emil Fischer. Experiments with dogs clearly showed sedative and hypnotic effect of the barbiturates and the oral administration of barbital (Veronal) confirmed the effect in humans. Barbital was commercialized in 1903 and in 1911 phenobarbital (Luminal) was introduced in the clinic, and this drug showed hypnotic and antiepileptic effects. Thereafter a lot of new barbiturates appeared. Dangerous properties of the drugs were recognized as abuse, addiction, and poisoning. An optimum treatment of acute barbiturate intoxication was obtained by the "Scandinavian method", which was developed in the Poison Centre of the Bispebjerg Hospital in Copenhagen. The centre was established by Carl Clemmesen in 1949 and the intensive care treatment reduced the mortality of the admitted persons from 20% to less than 2%. To-day only a few barbiturates are used in connection with anaesthesia and for the treatment of epilepsy

  10. [On the history of barbiturates].

    PubMed

    Norn, Svend; Permin, Henrik; Kruse, Edith; Kruse, Poul R

    2015-01-01

    Throughout the history of humanity, numerous therapeutic agents have been employed for their sedative and hypnotic properties such as opium, henbane (Hyoscyamus niger) and deadly nightshade (Atropa belladonna), but also alcohol and wine. In the 19th century potassium bromide was introduced as a sedative - and antiepileptic drug and chloral hydrate as sedative-hypnotics. A new era was reached by the introduction of barbiturates. The story started with the chemist Adolf von Baeyer. His breakthrough in the synthesis of new agents as barbituric acid and indigo and his education of young chemists was of great importance for the science of organic chemistry and the development of the dye and medicine industry in the late 19th century. The next important step was the development of barbiturates. The pioneers were Josef von Mering and Emil Fischer. Using the Grimaux-method they synthesized various barbiturates. It was von Mering who got the idea of introducing ethyl groups in the inactive barbituric acid to obtain sedatives, but the synthesis was succeeded by the chemist Emil Fischer. Experiments with dogs clearly showed sedative and hypnotic effect of the barbiturates and the oral administration of barbital (Veronal) confirmed the effect in humans. Barbital was commercialized in 1903 and in 1911 phenobarbital (Luminal) was introduced in the clinic, and this drug showed hypnotic and antiepileptic effects. Thereafter a lot of new barbiturates appeared. Dangerous properties of the drugs were recognized as abuse, addiction, and poisoning. An optimum treatment of acute barbiturate intoxication was obtained by the "Scandinavian method", which was developed in the Poison Centre of the Bispebjerg Hospital in Copenhagen. The centre was established by Carl Clemmesen in 1949 and the intensive care treatment reduced the mortality of the admitted persons from 20% to less than 2%. To-day only a few barbiturates are used in connection with anaesthesia and for the treatment of epilepsy

  11. Barbiturate intoxication and overdose

    MedlinePlus

    Intoxication - barbiturates ... Symptoms of barbiturate intoxication and overdose include: Altered level of consciousness Difficulty in thinking Drowsiness or coma Faulty judgment Lack of coordination Shallow ...

  12. 44 CFR 15.9 - Alcoholic beverages and narcotics.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.9 Alcoholic beverages and narcotics. At both Mt. Weather and the..., barbiturates or amphetamines onto the premises unless the Assistant Administrator, the Mt. Weather...

  13. 44 CFR 15.9 - Alcoholic beverages and narcotics.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., DEPARTMENT OF HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.9 Alcoholic beverages and narcotics. At both Mt. Weather and the..., barbiturates or amphetamines onto the premises unless the Assistant Administrator, the Mt. Weather...

  14. 44 CFR 15.9 - Alcoholic beverages and narcotics.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.9 Alcoholic beverages and narcotics. At both Mt. Weather and the..., barbiturates or amphetamines onto the premises unless the Assistant Administrator, the Mt. Weather...

  15. 44 CFR 15.9 - Alcoholic beverages and narcotics.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.9 Alcoholic beverages and narcotics. At both Mt. Weather and the..., barbiturates or amphetamines onto the premises unless the Assistant Administrator, the Mt. Weather...

  16. 44 CFR 15.9 - Alcoholic beverages and narcotics.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., DEPARTMENT OF HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.9 Alcoholic beverages and narcotics. At both Mt. Weather and the..., barbiturates or amphetamines onto the premises unless the Assistant Administrator, the Mt. Weather...

  17. Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats

    PubMed Central

    Uban, Kristina A.; Comeau, Wendy L.; Bodnar, Tamara; Yu, Wayne K.; Weinberg, Joanne; Galea, Liisa A. M.

    2014-01-01

    Rationale Individuals with fetal alcohol spectrum disorder (FASD) are at increased risk for substance use disorders (SUD). In typically developing individuals, susceptibility to SUD is associated with alterations in dopamine and hypothalamic-pituitary-adrenal (HPA) systems, and their interactions. Prenatal alcohol exposure (PAE) alters dopamine and HPA systems, yet effects of PAE on dopamine-HPA interactions are unknown. Amphetamine-stress cross-sensitization paradigms were utilized to investigate sensitivity of dopamine and stress (HPA) systems, and their interactions following PAE. Methods Adult Sprague-Dawley offspring from PAE, pair-fed, and ad libitum-fed control groups were assigned to amphetamine-(1–2mg/kg) or saline-treated conditions, with injections every other day for 15 days. 14 days later, all animals received an amphetamine challenge (1mg/kg) and 5 days later, hormones were measured under basal or acute stress conditions. Amphetamine sensitization (augmented locomotion, days 1–29) and cross-sensitization with acute restraint stress (increased stress hormones, day 34) were assessed. Results PAE rats exhibited a lower threshold for amphetamine sensitization compared to controls, suggesting enhanced sensitivity of dopaminergic systems to stimulant-induced changes. Cross-sensitization between amphetamine (dopamine) and stress (HPA hormone) systems was evident in PAE, but not in control rats. PAE males exhibited increased dopamine receptor expression (mPFC) compared to controls. Conclusions PAE alters induction and expression of sensitization/cross-sensitization, as reflected in locomotor, neural, and endocrine changes, in a manner consistent with increased sensitivity of dopamine and stress systems. These results provide insight into possible mechanisms that could underlie increased prevalence of SUD, as well as the impact of widely prescribed stimulant medications among adolescents with FASD. PMID:25420606

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

    PubMed

    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.

  19. Interactions of Enolizable Barbiturate Dyes.

    PubMed

    Schade, Alexander; Schreiter, Katja; Rüffer, Tobias; Lang, Heinrich; Spange, Stefan

    2016-04-11

    The specific barbituric acid dyes 1-n-butyl-5-(2,4-dinitro-phenyl) barbituric acid and 1-n-butyl-5-{4-[(1,3-dioxo-1H-inden-(3 H)-ylidene)methyl]phenyl}barbituric acid were used to study complex formation with nucleobase derivatives and related model compounds. The enol form of both compounds shows a strong bathochromic shift of the UV/Vis absorption band compared to the rarely coloured keto form. The keto-enol equilibria of the five studied dyes are strongly dependent on the properties of the environment as shown by solvatochromic studies in ionic liquids and a set of organic solvents. Enol form development of the barbituric acid dyes is also associated with alteration of the hydrogen bonding pattern from the ADA to the DDA type (A=hydrogen bond acceptor site, D=donor site). Receptor-induced altering of ADA towards DDA hydrogen bonding patterns of the chromophores are utilised to study supramolecular complex formation. As complementary receptors 9-ethyladenine, 1-n-butylcytosine, 1-n-butylthymine, 9-ethylguanidine and 2,6-diacetamidopiridine were used. The UV/Vis spectroscopic response of acid-base reaction compared to supramolecular complex formation is evaluated by (1)H NMR titration experiments and X-ray crystal structure analyses. An increased acidity of the barbituric acid derivative promotes genuine salt formation. In contrast, supramolecular complex formation is preferred for the weaker acidic barbituric acid. PMID:26945529

  20. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

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

    PubMed Central

    Wardle, Margaret C.; Marcus, Benjamin A.; de Wit, Harriet

    2015-01-01

    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

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

    PubMed

    Wardle, Margaret C; Marcus, Benjamin A; de Wit, Harriet

    2015-01-01

    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 of drugs.

  3. Substance use - amphetamines

    MedlinePlus

    Substance abuse - amphetamines; Drug abuse - amphetamines; Drug use - amphetamines ... There are different kinds of street amphetamines. Common ones ... Dextroamphetamine (ADHD medicine used illegally): dexies, kiddie- ...

  4. Amphetamines and Barbiturates: The Up and Down Drugs

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Part of "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  5. Respiratory complications during artificial barbiturate coma.

    PubMed

    Ducati, A; Signoroni, G; Meli, M; Lobascio, A E; Massei, R; Infuso, L

    1981-01-01

    Artificial barbiturate coma was induced in 13 patients with disorders of consciousness from traumatic or spontaneous diseases. Early respiratory complications consisting with Adult Respiratory Distress Syndrome (ARDS) were found in 10 out of these 13 patients; on the contrary, only 2 out of 13 patients, treated with routine intensive care therapy without barbiturate, showed analogous respiratory complications. The literature on the subject and the possible pathophysiological mechanism of respiratory distress are discussed.

  6. 21 CFR 862.3150 - Barbiturate test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Barbiturate test system. 862.3150 Section 862.3150...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3150 Barbiturate test system. (a) Identification. A barbiturate test system is a device intended...

  7. 21 CFR 862.3150 - Barbiturate test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Barbiturate test system. 862.3150 Section 862.3150...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3150 Barbiturate test system. (a) Identification. A barbiturate test system is a device intended...

  8. 21 CFR 862.3150 - Barbiturate test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Barbiturate test system. 862.3150 Section 862.3150...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3150 Barbiturate test system. (a) Identification. A barbiturate test system is a device intended...

  9. 21 CFR 862.3150 - Barbiturate test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Barbiturate test system. 862.3150 Section 862.3150...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3150 Barbiturate test system. (a) Identification. A barbiturate test system is a device intended...

  10. 38 CFR 1.218 - Security and law enforcement at VA facilities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the influence of alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited. Entering property under the influence of any narcotic drug, hallucinogen, marijuana... property of any narcotic drug, hallucinogen, marijuana, barbiturate, or amphetamine (unless prescribed by...

  11. 38 CFR 1.218 - Security and law enforcement at VA facilities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the influence of alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited. Entering property under the influence of any narcotic drug, hallucinogen, marijuana... property of any narcotic drug, hallucinogen, marijuana, barbiturate, or amphetamine (unless prescribed by...

  12. 38 CFR 1.218 - Security and law enforcement at VA facilities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the influence of alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited. Entering property under the influence of any narcotic drug, hallucinogen, marijuana... property of any narcotic drug, hallucinogen, marijuana, barbiturate, or amphetamine (unless prescribed by...

  13. 38 CFR 1.218 - Security and law enforcement at VA facilities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the influence of alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines is prohibited. Entering property under the influence of any narcotic drug, hallucinogen, marijuana... property of any narcotic drug, hallucinogen, marijuana, barbiturate, or amphetamine (unless prescribed by...

  14. Historical aspects and applications of barbituric acid derivatives. A review.

    PubMed

    Guillén Sans, R; Guzmán Chozas, M

    1988-12-01

    This review considers the pharmacological and other applications of barbituric and 2-thiobarbituric acid derivatives. A chronological description about the discovery, structural studies and first clinical assays are given. Therapeutic expectations as anticonvulsant, antimicrobial, spasmolytic, antiinflammatory, antitumoral and some other effects of 5,5-disubstituted barbituric acids and alkylidene- or arylidenebarbituric acids are overviewed. A considerable amount of these types of compounds have been proposed as industrial dyes and pigments, photosensitizers and thermosensitive materials. PMID:3073393

  15. Synthesis of carboranyl amino acids, hydantoins, and barbiturates

    SciTech Connect

    Wyzlic, I.M.; Tjarks, W.; Soloway, A.H.

    1996-07-31

    The syntheses of three novel boronated hydantoins, 5-(o-carboran-1-ylmethyl)hydantoin, 14, the tetraphenylphosphonium salt of 7-(hydantoin-5-ylmethyl)dodecahydro-7,8-dicarba-nido-undecaborate, 15, 5-(o-carboran-1-ylmethyl)-2-thiohydantoin, 16, and two new barbiturates, 5,5-bis(but-2-ynyl)barbiturate, 18, and 5,5-bis[(2-methyl-0-carboran-1-yl)methyl]barbiturate, 20, are described. Hydantoins 14-16 were synthesized from o-carboranylalanine (Car, 13). The detailed synthesis of Car and two other carborane-containing amino acids, O-(o-carboran-1-ylmethyl)tyrosine (CBT, 5a) and p-(o-carboran-1-yl)phenylalanine (CBPA, 5b), presented earlier as a communication, {sup 16} are also described. Hydantoin 14 and barbiturates 18 and 20 were tested for their potential anticonvulsant activity. Initial qualitative screening showed moderate activities for hydantoin 14 and barbiturate 18. Barbiturate 20 had no activity. Compound 14 appeared to be nontoxic at doses of 300 mg/kg (mice, ip) and 50 mg/kg (rats, oral). However, 18 was very toxic under similar conditions.

  16. Amphetamines, Barbiturates and Hallucinogens; An Analysis of Use, Distribution, and Control. Final Report.

    ERIC Educational Resources Information Center

    McGlothlin, William H.

    This report is the third of three monographs to provide perspectives on the use, distribution, and control of illicit drugs. The first, conducted in 1971, described the prevalence, use patterns, sources, distribution, and economics of the marihuana market. The second (1972) estimated the cost, benefits, and potential of approaches to narcotic…

  17. Extracorporeal treatment for barbiturate poisoning: recommendations from the EXTRIP Workgroup.

    PubMed

    Mactier, Robert; Laliberté, Martin; Mardini, Joelle; Ghannoum, Marc; Lavergne, Valery; Gosselin, Sophie; Hoffman, Robert S; Nolin, Thomas D

    2014-09-01

    The EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup conducted a systematic review of barbiturate poisoning using a standardized evidence-based process to provide recommendations on the use of extracorporeal treatment (ECTR) in patients with barbiturate poisoning. The authors reviewed all articles, extracted data, summarized key findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 617 articles met the search inclusion criteria. Data for 538 patients were abstracted and evaluated. Only case reports, case series, and nonrandomized observational studies were identified, yielding a low quality of evidence for all recommendations. Using established criteria, the workgroup deemed that long-acting barbiturates are dialyzable and short-acting barbiturates are moderately dialyzable. Four key recommendations were made. (1) The use of ECTR should be restricted to cases of severe long-acting barbiturate poisoning. (2) The indications for ECTR in this setting are the presence of prolonged coma, respiratory depression necessitating mechanical ventilation, shock, persistent toxicity, or increasing or persistently elevated serum barbiturate concentrations despite treatment with multiple-dose activated charcoal. (3) Intermittent hemodialysis is the preferred mode of ECTR, and multiple-dose activated charcoal treatment should be continued during ECTR. (4) Cessation of ECTR is indicated when clinical improvement is apparent. This report provides detailed descriptions of the rationale for all recommendations. In summary, patients with long-acting barbiturate poisoning should be treated with ECTR provided at least one of the specific criteria in the first recommendation is present.

  18. The Combined Effects of Ethanol and Amphetamine Sulfate on Performance of Human Subjects

    PubMed Central

    Wilson, Lolita; Taylor, Jack D.; Nash, Charles W.; Cameron, Donald F.

    1966-01-01

    The combined effects of ethanol and amphetamine on the performance of selected tests were evaluated. No differences were shown between the effects of ethanol-amphetamine and ethanol-lactose on the performance of balance, skipping, Minnesota manipulation, Purdue peg board, Maudsley Personality Inventory, pursuit rotor or digit span tests; but ethanol plus amphetamine produced less impairment of performance of coding, mental addition, and trail making tests than did ethanol plus a placebo. Ethanol increased the errors in performance of the Wonderlic Personnel Test, but the simultaneous administration of amphetamine did not reduce this effect. Conversely, amphetamine reduced the test-retest reliability of the Wonderlic Personnel Test, but alcohol appeared to counteract this effect of amphetamine. These experiments indicate that, when ethanol and amphetamine are used together, each drug modifies some of the effects produced by the other in a manner that cannot be predicted on the assumption that a depressant versus stimulant competition is operative. PMID:5324976

  19. The history of barbiturates a century after their clinical introduction

    PubMed Central

    López-Muñoz, Francisco; Ucha-Udabe, Ronaldo; Alamo, Cecilio

    2005-01-01

    The present work offers an analysis of the historical development of the discovery and use of barbiturates in the field of psychiatry and neurology, a century after their clinical introduction. Beginning with the synthesis of malonylurea by von Baeyer in 1864, and up to the decline of barbiturate therapy in the 1960s, it describes the discovery of the sedative properties of barbital, by von Mering and Fischer (1903), the subsequent synthesis of phenobarbital by this same group (1911), and the gradual clinical incorporation of different barbiturates (butobarbital, amobarbital, secobarbital, pentobarbital, thiopental, etc). We describe the role played in therapy by barbiturates throughout their history: their traditional use as sedative and hypnotic agents, their use with schizophrenic patients in so-called “sleep cures” (Klaesi, Cloetta), the discovery of the antiepileptic properties of phenobarbital (Hauptmann) and their use in the treatment of epilepsy, and the introduction of thiobarbiturates in intravenous anesthesia (Lundy, Waters). We also analyze, from the historical perspective, the problems of safety (phenomena of dependence and death by overdose) which, accompanied by the introduction of a range of psychoactive drugs in the 1950s, brought an end to barbiturate use, except in specific applications, such as the induction of anesthesia and the treatment of certain types of epileptic crisis. PMID:18568113

  20. An interesting case of barbiturate automatism and review of literature.

    PubMed

    Gokhale, Sankalp; Ramos-Estebanez, Ciro

    2013-01-01

    A 48 year old man with a diagnosis of HIV infection since 1993, on highly active anti-retro viral therapy (HAART) with stable CD4 count and undetectable viral load for years and seizure disorder presented with recurrent drowsiness. His seizures were well controlled on phenobarbitone for years. Repeated laboratory evaluation demonstrated toxic levels of phenobarbitone in his blood. A thorough clinical, psychiatric, laboratory and imaging evaluation did not reveal any obvious etiology for the recurrent barbiturate intoxication in this man. Our findings suggest the possible diagnosis of barbiturate drug automatism in this patient. Though drug automatism is a controversial entity, it merits continued attention. There are recent reports of similar phenomenon with newer sedative agents such as Zolpidem. It is important to be aware of this phenomenon as a possible explanation for recurrent intoxication with barbiturates without a clear etiology for drug overdose. PMID:24222872

  1. Amphetamine margin in sports

    SciTech Connect

    Laties, V.G.; Weiss, B.

    1981-10-01

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

  2. Comparative Actions of Barbiturates Studied by Pollen Grain Germination.

    ERIC Educational Resources Information Center

    Kordan, Herbert A.; Mumford, Pauline M.

    1979-01-01

    Describes a simple experimental system whereby the comparative actions of long, medium, and short-acting barbiturates can be demonstrated in a relatively short period of time under optical microscopy using pollen grains as the biological test or assay system. (Author/HM)

  3. Levo(-) amphetamine and dextro(+) amphetamine in the treatment of narcolepsy.

    PubMed

    Parkes, J D; Fenton, G W

    1973-12-01

    The narcoleptic syndrome is a life-long and sometimes familial disorder in which there is a disturbance of the rapid eye movement phase of sleep. Patients with periodic sleep in the daytime but no other symptoms seldom develop the narcoleptic syndrome and have a separate unrelated disorder. Twelve patients with the narcoleptic syndrome were treated separately with l(-) amphetamine and d(+) amphetamine. Both drugs abolished narcolepsy, d(+) amphetamine being slightly more potent than l(-) amphetamine. In equipotent doses, unwanted effects of nervousness and insomnia were equal in frequency. No tolerance to either preparation developed during a six month period. Cataplexy was not affected by amphetamine treatment, but was abolished in two patients when clomipramine was given together with either amphetamine. PMID:4359162

  4. PPL catalyzed four-component PASE synthesis of 5-monosubstituted barbiturates: Structure and pharmacological properties.

    PubMed

    Bihani, Manisha; Bora, Pranjal P; Verma, Alakesh K; Baruah, Reshita; Boruah, Hari Prasanna Deka; Bez, Ghanashyam

    2015-12-15

    Enzymatic four-component reactions are very rare although three-component enzymatic promiscuous reactions are widely reported. Herein, we report an efficient PASE protocol for the synthesis of potentially lipophilic zwitterionic 5-monosubstituted barbiturates by four component reaction of mixture of ethyl acetoacetate, hydrazine hydrate, aldehyde and barbituric acid in ethanol at room temperature. Seven different lipases were screened for their promiscuous activity towards the synthesis of 5-monosubstituted barbiturates and the lipase from porcine pancreas (PPL) found to give optimum efficiency. The zwitterionic 5-monosubstituted barbiturates with pyrazolyl ring showed promising pharmacological activity upon screening for antibacterial and apoptotic properties. PMID:26546212

  5. Alcohol

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Alcohol KidsHealth > For Teens > Alcohol Print A A A ... you can make an educated choice. What Is Alcohol? Alcohol is created when grains, fruits, or vegetables ...

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

    PubMed Central

    Vo, Kim; Neafsey, Patricia J; Lin, Carolyn A

    2015-01-01

    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. PMID:25653508

  7. New barbiturates and thiobarbiturates as potential enzyme inhibitors.

    PubMed

    Qureshi, Ashfaq M; Mumtaz, Saira; Rauf, Abdul; Ashraf, Muhammad; Nasar, Rumana; Chohan, Zahid H

    2015-02-01

    A series of 27 new barbiturates and thiobarbiturates have been synthesized by a convenient multi-component reaction in overall excellent yields (87-96%). All the synthesized compounds were characterized by 1H, 13C NMR, EIMS and elemental analysis (C, H, N and S). Furthermore, all compounds were screened for in vitro antioxidant (DPPH radical scavenging), lipoxygenase, chymotrypsin, α-glucosidase and anti-urease activities. Out of the series, 23 in DPPH, 14 in lipoxygenase, 2 in chymotrypsin have shown appreciable IC50 values.

  8. Criminal responsibility in amphetamine psychosis.

    PubMed

    Fukushima, A

    1994-01-01

    Historical changes in forensic psychiatric evaluation on criminal responsibility and proceedings in psychopathological findings of amphetamine psychosis are reviewed at first. The classification of amphetamine related mental disorders are proposed in 6 types. Among them, the clinical characteristics and psychopathological features of "Anxiety-situational reaction type" (Fukushima) are described. According to some reasonable grounds, offenders diagnosed as anxiety-situational reaction type should be evaluated as diminished responsibility in place of irresponsibility. Finally, two cases of murder committed under the influence of amphetamine, are reported in detail.

  9. Alcohol

    MedlinePlus

    ... Text Size: A A A Listen En Español Alcohol Wondering if alcohol is off limits with diabetes? Most people with diabetes can have a moderate amount of alcohol. Research has shown that there can be some ...

  10. Alcohol

    MedlinePlus

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  11. Alcohol

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Alcohol KidsHealth > For Kids > Alcohol Print A A A Text Size What's in ... What Is Alcoholism? Say No en español El alcohol Getting the Right Message "Hey, who wants a ...

  12. The ergogenic effect of amphetamine

    PubMed Central

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

    2014-01-01

    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 maximal oxygen consumption (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 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. PMID:27570800

  13. Alcoholism

    PubMed Central

    Girard, Donald E.; Carlton, Bruce E.

    1978-01-01

    There are important measurements of alcoholism that are poorly understood by physicians. Professional attitudes toward alcoholic patients are often counterproductive. Americans spend about $30 billion on alcohol a year and most adults drink alcohol. Even though traditional criteria allow for recognition of the disease, diagnosis is often made late in the natural course, when intervention fails. Alcoholism is a major health problem and accounts for 10 percent of total health care costs. Still, this country's 10 million adult alcoholics come from a pool of heavy drinkers with well defined demographic characteristics. These social, cultural and familial traits, along with subtle signs of addiction, allow for earlier diagnosis. Although these factors alone do not establish a diagnosis of alcoholism, they should alert a physician that significant disease may be imminent. Focus must be directed to these aspects of alcoholism if containment of the problem is expected. PMID:685264

  14. Induction by barbiturates of a cytochrome P-450-dependent fatty acid monooxygenase in Bacillus megaterium: relationship between barbiturate structure and inducer activity.

    PubMed

    Kim, B H; Fulco, A J

    1983-11-15

    In a recent communication (Narhi, L. and Fulco, A.J. [1982] J. Biol. Chem. 257, 2147-2150) we found that a soluble cytochrome P-450-dependent fatty acid monooxygenase isolated from Bacillus megaterium ATCC 14581 could be induced about 28-fold by phenobarbital. We have now examined 19 barbiturates and found that 13 significantly induce the specific monooxygenase activity. Of these, 11 are more active than phenobarbital and three (secobarbital, thiamylal and methohexital) are more than 30 times as active on a molar basis. The dialkyl barbiturates without exception show an excellent correlation between increasing lipophilicity and increasing potency as inducers as do most of the barbiturates containing an aromatic substituent. Nevertheless, it is apparent that certain structural features involving factors other than lipophilicity are also necessary for induction. Our finding that barbiturates can cause the non-substrate induction of a cytochrome P-450-dependent monooxygenase in a prokaryote represents a unique discovery that may provide a relatively simple model for apparently similar induction systems in higher animals. PMID:6418172

  15. Alcohol.

    ERIC Educational Resources Information Center

    Schibeci, Renato

    1996-01-01

    Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)

  16. Anti-motion-sickness therapy. [amphetamine preparation effects in human acceleration tolerance

    NASA Technical Reports Server (NTRS)

    Wood, C. D.

    1973-01-01

    Neither alterations in environmental temperature nor moderate intake of alcohol was found to alter susceptibility to motion sickness in subjects exposed to rotation in the Pensacola slow rotation room. Scopolamine with d-amphetamine was found to be the most effective preparation for the prevention of motion sickness under the experimental conditions of the studies reported here. Promethazine in combination with d-amphetamine was in the same range of effectiveness. Drug actions suggest that acetylcholine and norepinephrine may be involved in motion sickness.

  17. Barbiturate bearing aroylhydrazine derivatives: Synthesis, NMR investigations, single crystal X-ray studies and biological activity

    NASA Astrophysics Data System (ADS)

    Giziroglu, Emrah; Sarikurkcu, Cengiz; Aygün, Muhittin; Basbulbul, Gamze; Soyleyici, H. Can; Firinci, Erkan; Kirkan, Bulent; Alkis, Ayse; Saylica, Tayfur; Biyik, Halil

    2016-03-01

    A series of barbituric acid aroylhydrazine derivatives have been prepared from their corresponding 1,3-dimethyl-5-acetyl barbituric acid and aroylhydrazines. All compounds have been fully characterized by using FT-IR, multinuclear NMR (1H, 13C) and Mass (MS) spectrometry. We also describe the X-ray crystal structure of 3a, which crystallizes in the monoclinic P21/n space group. The crystal structure is stabilized with infinite linear chains of dimeric units. Furthermore, all compounds were investigated for their tyrosinase inhibition, antioxidative and antimicrobial activies. The results from biological activity assays have shown that all of compounds have excellent antioxidant, significant tyrosinase inhibition and moderate antimicrobial activity.

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

    ERIC Educational Resources Information Center

    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, (2)…

  19. Amphetamine Abuse Related Acute Myocardial Infarction

    PubMed Central

    Lewis, O'Dene; Kumar, Rajan; Yeruva, Sri Lakshmi Hyndavi; Curry, Bryan H.

    2016-01-01

    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. PMID:26998366

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

    PubMed

    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

  1. Amphetamine enhances endurance by increasing heat dissipation.

    PubMed

    Morozova, Ekaterina; Yoo, Yeonjoo; Behrouzvaziri, Abolhassan; Zaretskaia, Maria; Rusyniak, Daniel; Zaretsky, Dmitry; Molkov, Yaroslav

    2016-09-01

    Athletes use amphetamines to improve their performance through largely unknown mechanisms. Considering that body temperature is one of the major determinants of exhaustion during exercise, we investigated the influence of amphetamine on the thermoregulation. To explore this, we measured core body temperature and oxygen consumption of control and amphetamine-trea ted rats running on a treadmill with an incrementally increasing load (both speed and incline). Experimental results showed that rats treated with amphetamine (2 mg/kg) were able to run significantly longer than control rats. Due to a progressively increasing workload, which was matched by oxygen consumption, the control group exhibited a steady increase in the body temperature. The administration of amphetamine slowed down the temperature rise (thus decreasing core body temperature) in the beginning of the run without affecting oxygen consumption. In contrast, a lower dose of amphetamine (1 mg/kg) had no effect on measured parameters. Using a mathematical model describing temperature dynamics in two compartments (the core and the muscles), we were able to infer what physiological parameters were affected by amphetamine. Modeling revealed that amphetamine administration increases heat dissipation in the core. Furthermore, the model predicted that the muscle temperature at the end of the run in the amphetamine-treated group was significantly higher than in the control group. Therefore, we conclude that amphetamine may mask or delay fatigue by slowing down exercise-induced core body temperature growth by increasing heat dissipation. However, this affects the integrity of thermoregulatory system and may result in potentially dangerous overheating of the muscles.

  2. Amphetamine enhances endurance by increasing heat dissipation.

    PubMed

    Morozova, Ekaterina; Yoo, Yeonjoo; Behrouzvaziri, Abolhassan; Zaretskaia, Maria; Rusyniak, Daniel; Zaretsky, Dmitry; Molkov, Yaroslav

    2016-09-01

    Athletes use amphetamines to improve their performance through largely unknown mechanisms. Considering that body temperature is one of the major determinants of exhaustion during exercise, we investigated the influence of amphetamine on the thermoregulation. To explore this, we measured core body temperature and oxygen consumption of control and amphetamine-trea ted rats running on a treadmill with an incrementally increasing load (both speed and incline). Experimental results showed that rats treated with amphetamine (2 mg/kg) were able to run significantly longer than control rats. Due to a progressively increasing workload, which was matched by oxygen consumption, the control group exhibited a steady increase in the body temperature. The administration of amphetamine slowed down the temperature rise (thus decreasing core body temperature) in the beginning of the run without affecting oxygen consumption. In contrast, a lower dose of amphetamine (1 mg/kg) had no effect on measured parameters. Using a mathematical model describing temperature dynamics in two compartments (the core and the muscles), we were able to infer what physiological parameters were affected by amphetamine. Modeling revealed that amphetamine administration increases heat dissipation in the core. Furthermore, the model predicted that the muscle temperature at the end of the run in the amphetamine-treated group was significantly higher than in the control group. Therefore, we conclude that amphetamine may mask or delay fatigue by slowing down exercise-induced core body temperature growth by increasing heat dissipation. However, this affects the integrity of thermoregulatory system and may result in potentially dangerous overheating of the muscles. PMID:27604402

  3. Barbituric acid-based magnetic N-halamine nanoparticles as recyclable antibacterial agents.

    PubMed

    Dong, Alideertu; Sun, Yue; Lan, Shi; Wang, Qin; Cai, Qian; Qi, Xiuzhen; Zhang, Yanling; Gao, Ge; Liu, Fengqi; Harnoode, Chokto

    2013-08-28

    Novel recyclable bactericidal materials, barbituric acid-based magnetic N-halamine nanoparticles (BAMNH NPs), were fabricated by coating of magnetic silica nanoparticles (MS NPs) with barbituric acid-based N-halamine by the aid of the radical polymerization. The sterilizing effect on the bacterial strain is investigated by incubating Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis). The as-prepared BAMNH NPs exhibit higher biocidal activity than the bulk powder barbituric acid-based N-halamine due to the high activated surface area. The structural effect of N-halamine on antimicrobial performance was fully clarified through the comparison between BAMNH NPs and hydantoin-based magnetic N-halamine nanoparticles (HMNH NPs). BAMNH NPs exhibited promising stability toward repeated washing and long-term storage. BAMNH NPs with different chlorine content were comparatively chosen to investigate the influence of chlorine content on the antimicrobial activity. An antibacterial recycle experiment revealed that no significant change occurred in the structure and antibacterial efficiency of BAMNH NPs after five recycle experiments. The combination of barbituric acid-based N-halamine with magnetic component results in an obvious synergistic effect and facilitates the repeated antibacterial applications, providing potential and ideal candidates for sterilization or even for the control of disease.

  4. Barbiturate ingestion in three adult captive tigers (Panthera tigris) and concomitant fatal botulism of one.

    PubMed

    Williams, J H; Bester, L; Venter, L; Pretorius, D; Greyling, F

    2011-12-01

    Zoo animals, including tigers, have been reported to suffer from barbiturate intoxication, with pentabarbitone being most commonly recorded. Clinical signs range from mild ataxia to general anaesthesia with recovery over hours to days with several factors affecting hepatic barbiturate metabolism and tissue partitioning. Botulism is an often fatal intoxication in man, animals, birds and certain fish. The occurrence in carnivores is uncommon to rare, with only 2 reports found of botulism in felids. This report relates to 3 adult captive cohabiting tigers that simultaneously developed signs of abdominal discomfort, progressive ataxia, recumbency and comatose sleep resembling stage 2 anaesthesia, alternating with periods of distracted wakefulness and ataxic movements. These signs occurred 4 days after being fed the carcass of a horse that had ostensibly died of colic and not been euthanased. The male tiger that was the dominant animal in the feeding hierarchy was worst affected and had to be given intravenous fluids. The female that was lowest in hierarchy was unaffected. After 48-72 hours of treatment at the Onderstepoort Veterinary Academic Hospital the females could eat and made an uneventful recovery. The male tiger showed partial recovery but died during the night a few hours after drinking water on his return to the owner. Necropsy revealed severe oesophageal dilation and impaction with decaying grass; some of this material and water were present in the pharynx and trachea, and had been aspirated causing acute widespread bronchopneumonia. Colon content tested negative for common pesticides but, together with liver, tested positive for barbiturate. Serum taken on the day of admission had tested negative for barbiturate and the residual serum from the 3 animals later tested negative for botulinum toxin. Colon and oesophageal content from the male at necropsy were positive for Clostridium botulinum toxin type C by the mouse bioassay neutralisation test, confirming

  5. Amphetamine

    MedlinePlus

    ... for a limited period of time (a few weeks) along with a reduced calorie diet and an ... dose gradually, not more often than once every week. Follow these directions carefully.The medication in each ...

  6. Levo(−) amphetamine and dextro(+) amphetamine in the treatment of narcolepsy

    PubMed Central

    Parkes, J. D.; Fenton, G. W.

    1973-01-01

    The narcoleptic syndrome is a life-long and sometimes familial disorder in which there is a disturbance of the rapid eye movement phase of sleep. Patients with periodic sleep in the daytime but no other symptoms seldom develop the narcoleptic syndrome and have a separate unrelated disorder. Twelve patients with the narcoleptic syndrome were treated separately with l(−) amphetamine and d(+) amphetamine. Both drugs abolished narcolepsy, d(+) amphetamine being slightly more potent than l(−) amphetamine. In equipotent doses, unwanted effects of nervousness and insomnia were equal in frequency. No tolerance to either preparation developed during a six month period. Cataplexy was not affected by amphetamine treatment, but was abolished in two patients when clomipramine was given together with either amphetamine. PMID:4359162

  7. 10 CFR 26.405 - Drug and alcohol testing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... recordable under the Department of Labor standards contained in 29 CFR 1904.7, and subsequent amendments... alcohol testing requirements of 49 CFR Part 40 and subsequent amendments thereto. (f) Testing of urine... metabolite, opiates (codeine, morphine, 6-acetylmorphine), amphetamines (amphetamine,...

  8. 10 CFR 26.405 - Drug and alcohol testing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... recordable under the Department of Labor standards contained in 29 CFR 1904.7, and subsequent amendments... alcohol testing requirements of 49 CFR Part 40 and subsequent amendments thereto. (f) Testing of urine... metabolite, opiates (codeine, morphine, 6-acetylmorphine), amphetamines (amphetamine,...

  9. 10 CFR 26.405 - Drug and alcohol testing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... recordable under the Department of Labor standards contained in 29 CFR 1904.7, and subsequent amendments... alcohol testing requirements of 49 CFR Part 40 and subsequent amendments thereto. (f) Testing of urine... metabolite, opiates (codeine, morphine, 6-acetylmorphine), amphetamines (amphetamine,...

  10. 10 CFR 26.405 - Drug and alcohol testing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... recordable under the Department of Labor standards contained in 29 CFR 1904.7, and subsequent amendments... alcohol testing requirements of 49 CFR Part 40 and subsequent amendments thereto. (f) Testing of urine... metabolite, opiates (codeine, morphine, 6-acetylmorphine), amphetamines (amphetamine,...

  11. Partial characterization of a barbiturate-induced cytochrome P-450-dependent fatty acid monooxygenase from Bacillus megaterium.

    PubMed

    Narhi, L O; Kim, B H; Stevenson, P M; Fulco, A J

    1983-11-15

    A soluble cytochrome P-450-dependent fatty acid monooxygenase activity obtained from Bacillus megaterium ATCC 14581 can be induced by at least 13 different barbiturates. In general, the potency of these compounds as inducers increases with their increasing lipophilicity. We have now shown that at least 4 of these barbiturates (phenobarbital, secobarbital, pentobarbital and methohexital) seem to induce the same active cytochrome P-450-containing enzyme by a non-substrate type mechanism. The partially purified enzymes obtained from cultures induced with each of the 4 barbiturates tested were all of similar molecular size (Mr = 130,000 +/- 10,000) and had similar turnover numbers (1400-1800 +/- 300) with either palmitoleate or myristate as substrates. None of the tested barbiturates served as substrates, activators or inhibitors of any of the monooxygenase preparations, nor did they appear to interact in any way with the monooxygenase enzyme or the P-450 component. PMID:6418173

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

    PubMed Central

    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

  13. 4-Methyl-amphetamine: a health threat for recreational amphetamine users.

    PubMed

    Blanckaert, P; van Amsterdam, Jgc; Brunt, Tm; van den Berg, Jdj; Van Durme, F; Maudens, K; van Bussel, Jch

    2013-09-01

    4-Methylamphetamine (4-MA) was originally developed as an appetite suppressant, but development was halted due to side effects. It has recently resurfaced as a new psychoactive substance in Europe, and is mostly found together with amphetamine. Around 11.5% of tested Dutch speed samples were positive for 4-MA. In Belgium, 4-MA was also found in speed samples. In 2011 and 2012, several fatal incidents after amphetamine use were observed in Belgium, the United Kingdom and The Netherlands. In all victims, toxicological analysis confirmed the presence of 4-MA, in addition to amphetamine. The observed blood amphetamine levels were too low to be fatal. Contrary to amphetamine, which displays noradrenergic and dopaminergic activity, 4-MA also shows serotonergic activity, which may contribute to the observed toxicity. Other mechanisms of toxicity are put forward in this paper as well. To conclude, the observed toxicity is most likely the result of the combined dopaminergic activity of amphetamine and the serotonergic activity of 4-MA. In addition, the presence of 4-MA may have dampened the psychoactive effects of amphetamine by attenuation of the amphetamine-induced dopamine release, potentially inclining users to ingest higher doses of contaminated speed. Also, slower metabolism of 4-MA and its MAO-inhibiting properties can also contribute to the unusual high toxicity of 4-MA.

  14. Amphetamine as a social drug: Effects of d-amphetamine on social processing and behavior

    PubMed Central

    Wardle, Margaret C.; Garner, Matthew J.; Munafò, Marcus R.; de Wit, Harriet

    2012-01-01

    Rationale Drug users often report using drugs to enhance social situations, and empirical studies support the idea that drugs increase both social behavior and the value of social interactions. One way drugs may affect social behavior is by altering social processing, for example by decreasing perceptions of negative emotion in others. Objectives We examined effects of d-amphetamine on processing of emotional facial expressions, and on the social behavior of talking. We predicted amphetamine would enhance attention, identification and responsivity to positive expressions, and that this in turn would predict increased talkativeness. Methods Over three sessions, 36 healthy normal adults received placebo, 10mg, and 20mg d-amphetamine under counterbalanced double-blind conditions. At each session we measured processing of happy, fearful, sad and angry expressions using an attentional visual probe task, a dynamic emotion identification task, and measures of facial muscle activity. We also measured talking. Results Amphetamine decreased the threshold for identifying all emotions, increased negative facial responses to sad expressions, and increased talkativeness. Contrary to our hypotheses, amphetamine did not alter attention to, identification of or facial responses to positive emotions specifically. Interestingly, the drug decreased the threshold to identify all emotions, and this effect was uniquely related to increased talkativeness, even after controlling for overall sensitivity to amphetamine. Conclusions The results suggest that amphetamine may encourage sociability by increasing sensitivity to subtle emotional expressions. These findings suggest novel social mechanisms that may contribute to the rewarding effects of amphetamine. PMID:22526538

  15. Supramolecular chiral host-guest nanoarchitecture induced by the selective assembly of barbituric acid derivative enantiomers.

    PubMed

    Sun, Xiaonan; Silly, Fabien; Maurel, Francois; Dong, Changzhi

    2016-10-21

    Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly. PMID:27623155

  16. The unusual solvatochromism and solvatofluorochromism of longwave absorbing and emitting barbiturate merocyanine dyes

    NASA Astrophysics Data System (ADS)

    Ishchenko, Alexander A.; Kulinich, Andrii V.

    2016-09-01

    Spectral-fluorescent properties of a series of merocyanine dyes comprising the barbituric acid residue as the electron-accepting terminal group are investigated in comparison with those of their N,N-methylated analogues in media of various polarity. It is revealed that in polar aprotic solvents the electronic absorption spectra of the studied compounds are influenced dramatically by the formation of hydrogen bonds between the NH-groups of barbituric residue and solvent molecules. An effect of such nucleophilic solvation on the electronic structure of the studied dyes is analysed using both the spectral data obtained and the DFT/B3LYP quantum chemical simulation. It is found also, that solvation has comparatively weak influence on the shape and position of the fluorescence bands of the studied merocyanines while the fluorescence quantum yield changes substantially in solvents of various polarity.

  17. Supramolecular chiral host-guest nanoarchitecture induced by the selective assembly of barbituric acid derivative enantiomers

    NASA Astrophysics Data System (ADS)

    Sun, Xiaonan; Silly, Fabien; Maurel, Francois; Dong, Changzhi

    2016-10-01

    Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly.

  18. Ultraviolet spectrophotometry of theophylline in plasma in the presence of barbiturates.

    PubMed

    Jatlow, P

    1975-09-01

    Ultraviolet spectrophotometry is widely used for the analysis of theophylline in blood, for purposes of monitoring therapy, and for pharmacokinetic studies. Phenobarbital, a component of common oral theophylline preparations, interferes with assays now in use. The modification of the method of Schack and Waxler [J. Pharmacol. Exp. Ther. 97, 283 (1949)] presented in this paper eliminates barbiturate interference. After solvent extraction and back extraction into NaOH, the pH of the alkaline solution is adjusted from pH 13 to 10 before spectrophotometric measurement. This shifts the barbiturate absorption maximum from 255 to 240 nm, permitting accurate analysis of theophylline, the spectrum of which is unaffected by the pH change.

  19. Acylureas: a new class of barbiturate-like bacterial cytochrome P-450 inducers.

    PubMed

    Ruettinger, R T; Kim, B H; Fulco, A J

    1984-10-16

    The soluble, cytochrome P-450-dependent fatty acid monooxygenase of Bacillus megaterium ATCC 14581 is induced by phenobarbital and at least twelve other barbiturates (Kim, B.-H. and Fulco, A.J. (1983) Biochem. Biophys. Res. Commun. 116, 843-850). We have since found that the inducer potency of phenobarbital and of six other of these barbiturates was enhanced by adding them to the growth medium prior to sterilization by autoclaving. A similar 'activation' was effected simply by autoclaving these barbiturates in distilled water at pH 8.0. When the hydrolytic products resulting from such treatment of phenobarbital were identified and screened for inducer activity, the major product, 2-phenylbutyrylurea, was found to be 3-5-times more potent than phenobarbital itself. The racemic mixture, (+/-)-2-phenylbutyrylurea was somewhat more active as an inducer than was either of the enantiomers [+/-) or (-] tested singly. Of the other hydrolytic products of phenobarbital, only 2-phenylbutyramide had significant inducer activity (about the same as phenobarbital). Among other ureides tested, two monosubstituted acetylureas (phenylacetylurea and dodecanoylurea) were inactive as inducers, but six of seven disubstituted acetylureas were better inducers than 2-phenylbutyrylurea. PMID:6435683

  20. Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

    SciTech Connect

    Savechenkov, Pavel Y.; Zhang, Xi; Chiara, David C.; Stewart, Deirdre S.; Ge, Rile; Zhou, Xiaojuan; Raines, Douglas E.; Cohen, Jonathan B.; Forman, Stuart A.; Miller, Keith W.; Bruzik, Karol S.

    2012-12-10

    We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray crystallography. Additionally, we obtained the {sup 3}H-labeled ligand with high specific radioactivity. R-(-)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC{sub 50} approaches those for propofol and etomidate, whereas S-(+)-14 is 10-fold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(-)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol in human {alpha}1{beta}2/3{gamma}2L GABA{sub A} receptors. Finally, R-(-)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both {alpha}1 and {beta}3 subunits of human {alpha}1{beta}3 GABAA receptors. These results indicate R-(-)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.

  1. Allyl m-trifluoromethyldiazirine mephobarbital: an unusually potent enantioselective and photoreactive barbiturate general anesthetic.

    PubMed

    Savechenkov, Pavel Y; Zhang, Xi; Chiara, David C; Stewart, Deirdre S; Ge, Rile; Zhou, Xiaojuan; Raines, Douglas E; Cohen, Jonathan B; Forman, Stuart A; Miller, Keith W; Bruzik, Karol S

    2012-07-26

    We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray crystallography. Additionally, we obtained the (3)H-labeled ligand with high specific radioactivity. R-(-)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC(50) approaches those for propofol and etomidate, whereas S-(+)-14 is 10-fold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(-)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol in human α1β2/3γ2L GABA(A) receptors. Finally, R-(-)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both α1 and β3 subunits of human α1β3 GABA(A) receptors. These results indicate R-(-)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.

  2. Green Synthesis and Urease Inhibitory Activity of Spiro-Pyrimidinethiones/Spiro-Pyrimidinones-Barbituric Acid Derivatives

    PubMed Central

    Mohammadi Ziarani, Ghodsi; Asadi, Shima; Faramarzi, Sakineh; Amanlou, Massoud

    2015-01-01

    Sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H) with pore size 6 nm as an efficient heterogeneous nanoporous solid acid catalyst exhibited good catalytic activity in the Biginelli-like reaction in the synthesis of spiroheterobicyclic rings with good yield and good recyclability. Spiro-pyrimidinethiones/spiro-pyrimidinones-barbituric acid derivatives were synthesized in a simple and efficient method using the one-pot three-component reaction of a cyclic 1,3- dicarbonyl compounds (barbituric acid), an aromatic aldehyde and urea or thiourea in the presence of nanoporous silica SBA-Pr-SO3H under solvent free conditions. Urease inhibitory activity of spiro compounds were tested against Jack bean urease using Berthelot alkaline phenol–hypochlorite method. Five of 13 compounds were inhibitor and two of them were enzyme activators. Analysis of the docking results showed that, in most of the spiro molecules, one of the carbonyl groups is coordinated with both nickel atoms, while the other one is involved in the formation of hydrogen bonds with important active-site residues. The effect of inserting two methyl groups on N atoms of barbiturate ring, S substituted, ortho, meta and para substituted compounds were investigated too. PMID:26664377

  3. 32 CFR 228.9 - Prohibition on narcotics and illegal substances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... narcotic drug, hallucinogen, marijuana, barbiturate or amphetamine is prohibited. Operation of a motor..., hallucinogens, marijuana, barbiturates or amphetamines is also prohibited. These prohibitions shall not apply...

  4. 32 CFR 228.9 - Prohibition on narcotics and illegal substances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... narcotic drug, hallucinogen, marijuana, barbiturate or amphetamine is prohibited. Operation of a motor..., hallucinogens, marijuana, barbiturates or amphetamines is also prohibited. These prohibitions shall not apply...

  5. 32 CFR 228.9 - Prohibition on narcotics and illegal substances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... narcotic drug, hallucinogen, marijuana, barbiturate or amphetamine is prohibited. Operation of a motor..., hallucinogens, marijuana, barbiturates or amphetamines is also prohibited. These prohibitions shall not apply...

  6. 32 CFR 228.9 - Prohibition on narcotics and illegal substances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... narcotic drug, hallucinogen, marijuana, barbiturate or amphetamine is prohibited. Operation of a motor..., hallucinogens, marijuana, barbiturates or amphetamines is also prohibited. These prohibitions shall not apply...

  7. 32 CFR 228.9 - Prohibition on narcotics and illegal substances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... narcotic drug, hallucinogen, marijuana, barbiturate or amphetamine is prohibited. Operation of a motor..., hallucinogens, marijuana, barbiturates or amphetamines is also prohibited. These prohibitions shall not apply...

  8. D-amphetamine and delinquency: hyperkinesis persisting?

    PubMed

    Maletzky, B M

    1974-12-01

    The clinical efficacy of d-amphetamine for delinquent behavior in adolescents and the relationships between such delinquency and hyperactivity of childhood were explored employing the methods of sequential analysis. Fourteen subject pairs of delinquent teenagers were examined, and a significant positive effect documented for d-amphetamine as compared to placebo when both were added to an ongoing psychotherapeutic regimen. Tolerance, withdrawal, and euphoria were not associated with d-amphetamine's use in the experimental subjects. Parallels were drawn between d-amphetamine' s effects in delinquent adolescents and hyperactive children; a re-analysis of the data demonstrated surprisingly close links between a history or presence of hyperactive traits and a clinical response to d-amphetamine. Difficulties in employing d-amphetamine in this age group are acknowledged and suggestions for further research offered. The notion that children "outgrow" hyperactivity may be simplistic: hyperactive children as teenagers may not be overly active; however, they continue to manifest behavioral difficulties, primarily of an antisocial nature. While this may be partially explained on the basis of negative aspects in their upbringing, there is some evidence of hereditary and neurologic mechanisms at fault. One method of documenting continuing neurologic dysfunction in the hyperactive child turned teenager is by direct examination. A number of investigators have demonstrated electroencephalographic abnormalities in juvenile delinquents, many of whom had histories of hyperactivity as children. More recently, this kind of individual has been shown to suffer some frontal lobe dysfunction and to manifest subtle, but definite, abnormalities on intensive neurological examination. Continuing central nervous system dysfunction in delinquency might also be demonstrated by pharmacologic means: should delinquent adolescents respond to drugs that help the hyperactive child, similar mechanisms

  9. 21 CFR 862.3100 - Amphetamine test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Amphetamine test system. 862.3100 Section 862.3100...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3100 Amphetamine test system. (a) Identification. An amphetamine test system is a device intended...

  10. 21 CFR 862.3100 - Amphetamine test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Amphetamine test system. 862.3100 Section 862.3100...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3100 Amphetamine test system. (a) Identification. An amphetamine test system is a device intended...

  11. 21 CFR 862.3100 - Amphetamine test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Amphetamine test system. 862.3100 Section 862.3100...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3100 Amphetamine test system. (a) Identification. An amphetamine test system is a device intended...

  12. [Substitution therapy tested against amphetamine dependence].

    PubMed

    Bloniecki Kallio, Victor; Guterstam, Joar; Franck, Johan

    2016-01-01

    Amphetamine dependence is relatively common in Sweden and it is the most frequently used substance among patients with intravenous drug abuse. Current treatment options are limited but recently substitution therapy with psychostimulant medication has been evaluated in several clinical trials. Such treatment is controversial in Sweden, perhaps due to the failure of experimental prescription of psychostimulants in the 1960s. Recent clinical trials however indicate that structured treatment programs with psychostimulants might have positive effects, although the results are inconsistent and the evidence base is still limited. Future research is needed in order to determine the potential role of substitution therapy for amphetamine dependence in clinical practice. PMID:26756343

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-08-01

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

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

    PubMed

    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.

  17. Amphetamine and extinction of cued fear.

    PubMed

    Carmack, Stephanie A; Wood, Suzanne C; Anagnostaras, Stephan G

    2010-01-01

    Much research is focused on developing novel drugs to improve memory. In particular, psychostimulants have been shown to enhance memory and have a long history of safe use in humans. In prior work, we have shown that very low doses of amphetamine administered before training on a Pavlovian fear-conditioning task can dramatically facilitate the acquisition of cued fear. The current experiment sought to expand these findings to the extinction of cued fear, a well-known paradigm with therapeutic implications for learned phobias and post-traumatic stress disorder. If extinction reflects new learning, one might expect drugs that enhance the acquisition of cued fear to also enhance the extinction of cued fear. This experiment examined whether 0.005 or 0.05 mg/kg of D-amphetamine (therapeutic doses shown to enhance acquisition) also enhance the extinction of cued fear. Contrary to our hypothesis, amphetamine did not accelerate extinction. Thus, at doses that enhance acquisition of conditioned fear, amphetamine does not appear to enhance extinction.

  18. Impaired DRL 30 performance during amphetamine withdrawal.

    PubMed

    Peterson, Jayms D; Wolf, Marina E; White, Francis J

    2003-07-14

    Repeated administration of psychomotor stimulants may produce an impulsive state that could contribute to the cycle of drug abstinence and relapse seen in human drug addicts. We have previously reported that the inhibitory effects of dopamine (DA) on the firing rate of medial prefrontal cortex (mPFC) neurons were reduced in rats after repeated amphetamine treatment suggesting impaired mPFC DA function. Here, we used a differential reinforcement of low rates of responding (DRL) operant conditioning task, which is dependent on mPFC DA, to test impulsivity and inhibitory control. Food-restricted rats were trained to inhibit a nose poke response for 30s before a subsequent nose poke would result in a food reward (DRL 30). Once training was completed, rats received 5 days of no treatment, daily i.p. saline injections or daily i.p. injections of 5mg/kg amphetamine. Nine days of DRL 30 test performance began following a 3-day withdrawal from treatment. The percent of training active hole nose pokes was significantly increased and the percent of training efficiency was significantly decreased in rats withdrawn from repeated amphetamine administration as compared to saline or nai;ve rats. This suggests that impulsivity is increased during amphetamine withdrawal, which we hypothesize is associated with disrupted DA function in the mPFC. PMID:12842301

  19. The use of flurazepam (dalmane) as a substitute for barbiturates and methaqualone/diphenhydramine (mandrax) in general practice.

    PubMed

    Rooke, K C

    1976-01-01

    A twelve-week study involving fifty-three patients is described as taking place in a practice with a higher than average geriatric population. The purpose of the study was to substitute flurazepam for habitually used barbiturates or methaqualone/diphenhydramine. Of the original fifty-three patients admitted to the study, fifty-one completed; the two drop-outs resulting from concomitant physical illness. Eighty-four per cent of patients were successfully changed to flurazepam. Of those who did not accept flurazepam, eight per cent accepted nitrazepam, while six per cent of patients were motivated to stop all hypnotics. During the three month period of the study none of the well-known disadvantages of the barbiturates and methaqualone/diphenhydramine were seen with flurazepam. The author found flurazepam to be a very efficient hypnotic of relatively low toxicity which could be easily substituted fro barbiturates and methaqualone/diphenhydramine in the treatment of long-term insomnia.

  20. Enantioselective Synthesis of Spirobarbiturate-Cyclohexenes through Phosphine-Catalyzed Asymmetric [4 + 2] Annulation of Barbiturate-Derived Alkenes with Allenoates.

    PubMed

    Liu, Honglei; Liu, Yang; Yuan, Chunhao; Wang, Guo-Peng; Zhu, Shou-Fei; Wu, Yang; Wang, Bo; Sun, Zhanhu; Xiao, Yumei; Zhou, Qi-Lin; Guo, Hongchao

    2016-03-18

    An enantioselective synthesis of pharmaceutically important spirobarbiturates has been achieved via spirocyclic chiral phosphine-catalyzed asymmetric [4 + 2] annulation of barbiturate-derived alkenes with allenoates. With the use of this tool, various spirobarbiturate-cyclohexenes are obtained in good to excellent yields with excellent diastereo- and enantioselectivities. A wide range of α-substituted allenoates and barbiturate-derived alkenes were tolerated.

  1. Structure-energy relationship in barbituric acid: a calorimetric, computational, and crystallographic study.

    PubMed

    Roux, María Victoria; Temprado, Manuel; Notario, Rafael; Foces-Foces, Concepción; Emel'yanenko, Vladimir N; Verevkin, Sergey P

    2008-08-14

    This paper reports the value of the standard (p(o) = 0.1 MPa) molar enthalpy of formation in the gas phase at T = 298.15 K for barbituric acid. The enthalpies of combustion and sublimation were measured by static bomb combustion calorimetry and transference (transpiration) method in a saturated N2 stream and a gas-phase enthalpy of formation value of -(534.3 +/- 1.7) kJ x mol(-1) was determined at T = 298.15 K. G3-calculated enthalpies of formation are in very good agreement with the experimental value. The behavior of the sample as a function of the temperature was studied by differential scanning calorimetry, and a new polymorph of barbituric acid at high temperature was found. In the solid state, two anhydrous forms are known displaying two out of the six hydrogen-bonding patterns observed in the alkyl/alkenyl derivatives retrieved from the Cambridge Crystallographic Database. The stability of these motifs has been analyzed by theoretical calculations. X-ray powder diffraction technique was used to establish to which polymorphic form corresponds to the commercial sample used in this study and to characterize the new form at high temperature. PMID:18646743

  2. Structure-energy relationship in barbituric acid: a calorimetric, computational, and crystallographic study.

    PubMed

    Roux, María Victoria; Temprado, Manuel; Notario, Rafael; Foces-Foces, Concepción; Emel'yanenko, Vladimir N; Verevkin, Sergey P

    2008-08-14

    This paper reports the value of the standard (p(o) = 0.1 MPa) molar enthalpy of formation in the gas phase at T = 298.15 K for barbituric acid. The enthalpies of combustion and sublimation were measured by static bomb combustion calorimetry and transference (transpiration) method in a saturated N2 stream and a gas-phase enthalpy of formation value of -(534.3 +/- 1.7) kJ x mol(-1) was determined at T = 298.15 K. G3-calculated enthalpies of formation are in very good agreement with the experimental value. The behavior of the sample as a function of the temperature was studied by differential scanning calorimetry, and a new polymorph of barbituric acid at high temperature was found. In the solid state, two anhydrous forms are known displaying two out of the six hydrogen-bonding patterns observed in the alkyl/alkenyl derivatives retrieved from the Cambridge Crystallographic Database. The stability of these motifs has been analyzed by theoretical calculations. X-ray powder diffraction technique was used to establish to which polymorphic form corresponds to the commercial sample used in this study and to characterize the new form at high temperature.

  3. Effects of deep barbiturate coma on acute spinal cord injury in the cat.

    PubMed

    Ducati, A; Schieppati, M; Giovanelli, M A

    1984-04-01

    The effects of barbiturate administration on experimental balloon-induced spinal cord injury were tested in cats. Somatosensory evoked potentials from sciatic nerve stimulation were obtained before trauma and every 60 minutes after it up to the sixth hour, when the animals were killed. Eight cats received no barbiturate treatment. On histologic examination the traumatic lesion was found to be extensive (mean, 72.8% of total cross section of the cord area), sparing dorsal columns only in six cats. Somatosensory evoked potentials were absent in two cats and profoundly modified (that is, the late waves were absent) in six cats at the sixth hour. Eight cats were given a continuous infusion for 1 hour of intravenous thiopental sodium (total dose, 65-90 mg/kg) starting 30 minutes after trauma. In these eight cats, the extent of the traumatic lesion was significantly reduced (8.8% of the cord area). Among them, three animals presented with unaltered somatosensory evoked potentials (that is, with the presence of both primary components and late waves) at the sixth hour. It was concluded that thiopental sodium improves the response of the spinal cord to trauma, both at an anatomic and at a functional level.

  4. Synthesis, characterization, thermal behaviour and single crystal X-ray analysis of two new insensitive high energy density materials [8-hydroxyquinolinium 5-(2,4,6-trinitrophenyl)barbiturate (I) and 8-hydroxyquinolinium 5-(5-chloro-2,4-dinitrophenyl)-1,3-dimethyl barbiturate (II)

    NASA Astrophysics Data System (ADS)

    Manickkam, V.; Devi, P. Poornima; Kalaivani, D.

    2014-12-01

    Barbiturates I and II have been synthesized as maroon red and red orange coloured solids by mixing the ethanolic solutions of 2-chloro-1,3,5-trinitrobenzene ( TNCB), pyrimidine-2,4,6(1 H,3 H,5 H)-trione [barbituric acid ( BA)] and 8-hydroxyquinoline and 1,3-dichloro-4,6-dinitrobenzene ( DCDNB), 1,3-dimethylpyrimidine-2,4,6(1 H,3 H,5 H)-trione(1,3-dimethylbarbituric acid) and 8-hydroxyquinoline respectively. The structures of these two barbiturates have been predicted from the spectral studies (UV-VIS, IR, 1H NMR, 13C NMR, mass) and elemental analysis. Qualitative tests have been carried out to infer the presence of nitrogen and nitro groups and also chlorine atom in barbiturate II. Slow evaporation of ethanol-dimethylsulphoxide/ethanol solutions of barbiturate I/barbiturate II at 293 K yielded good for X-Ray diffraction crystals. Single crystal X-ray diffraction studies of the crystals further confirm the putative structures of the barbiturates. The asymmetric unit of the barbiturate I comprises of 8-hydroxyquinolinium cation, 5-(2,4,6-trinitrophenyl) barbiturate anion and a molecule of dimethylsulphoxide (DMSO), which is used as a recrystallizing solvent. It crystallizes in the triclinic system with space group (centrosymmetric). Barbiturate II crystallizes in the orthorhombic system with space group P212121 (non-centrosymmetric). Barbiturates I and II are stable towards an impact sensitivity test, when a weight of 2 kg mass hammer is dropped from a height of 160 cm of the instrument. TGA/ DTA analyses at four different heating rates (5, 10, 20, and 40 K/min) imply that they undergo exothermic decomposition (˜85%) in three different stages between 273 and 873 K. Activation energies for these decomposition processes have been calculated by employing Kissinger and Ozawa plots. Impact sensitivity test and activation energies have revealed that the titled barbiturates are insensitive high energy density materials ( IHEDMS).

  5. Adderall® (amphetamine-dextroamphetamine) toxicity.

    PubMed

    Fitzgerald, Kevin T; Bronstein, Alvin C

    2013-02-01

    The American Psychiatric Association estimates that 3-7% of US school-aged children exhibit attention-deficit/hyperactivity disorder (ADHD). Adderall(®) (amphetamine dextroamphetamine) and a variety of brand names and generic versions of this combination are available by prescription to treat ADHD and narcolepsy. Both immediate and sustained release products are used as are single agent amphetamine medication. Knowing the exact agent ingested can provide information of dose labeled and length of clinical effects. These drugs are used off label by college students for memory enhancement, test taking ability, and for study marathons. These agents are DEA Schedule II controlled substances with high potential for abuse. For humans with ADHD or narcolepsy, standard recommended dosage is 5-60 mg daily. Amphetamine and its analogues stimulate the release of norepinephrine affecting both α- and β-adrenergic receptor sites. α-Adrenergic stimulation causes vasoconstriction and an increase in total peripheral resistance. β-Adrenergic receptor stimulation leads to an increase in heart rate, stroke volume, and skeletal muscle blood flow. Clinical signs of Adderall(®) overdose in humans and dogs include hyperactivity, hyperthermia, tachycardia, tachypnea, mydriasis, tremors, and seizures. In addition, Adderall intoxication in dogs has been reported to cause hyperthermia, hypoglycemia, hypersegmentation of neutrophils, and mild thrombocytopenia. Diagnosis can be confirmed by detecting amphetamine in stomach contents or vomitus, or by positive results obtained in urine tests for illicit drugs. Treatment is directed at controlling life-threatening central nervous system and cardiovascular signs. Seizures can be controlled with benzodiazepines, phenothiazines, pentobarbital, and propofol. Cardiac tachyarrhythmias can be managed with a β-blocker such as propranolol. Intravenous fluids counter the hyperthermia, assist in maintenance of renal function, and help promote the

  6. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors.

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

    ERIC Educational Resources Information Center

    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)

  8. Predictive indicators for adjustment in 4-year-old children whose mothers used amphetamine during pregnancy.

    PubMed

    Billing, L; Eriksson, M; Steneroth, G; Zetterström, R

    1988-01-01

    Psychosocial factors that could be used as predictive indicators for adjustment of 4-year-old children whose mothers had used amphetamine during pregnancy were studied by means of simple and multivariate correlation analyses. The following statistically significant correlations were found: Length of maternal alcohol and drug abuse during pregnancy was correlated negatively with the child's adjustment as were numbers of paternal criminal convictions, number of stress factors of the mother, and number of earlier children born to the mother. Paternal criminality was associated with the outcome, regardless of amount of contact between father and child.

  9. 21 CFR 862.3100 - Amphetamine test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Amphetamine test system. 862.3100 Section 862.3100...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems §...

  10. 21 CFR 862.3100 - Amphetamine test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Amphetamine test system. 862.3100 Section 862.3100...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems §...

  11. Enantioselective Synthesis of Spirobarbiturate-Cyclohexenes through Phosphine-Catalyzed Asymmetric [4 + 2] Annulation of Barbiturate-Derived Alkenes with Allenoates.

    PubMed

    Liu, Honglei; Liu, Yang; Yuan, Chunhao; Wang, Guo-Peng; Zhu, Shou-Fei; Wu, Yang; Wang, Bo; Sun, Zhanhu; Xiao, Yumei; Zhou, Qi-Lin; Guo, Hongchao

    2016-03-18

    An enantioselective synthesis of pharmaceutically important spirobarbiturates has been achieved via spirocyclic chiral phosphine-catalyzed asymmetric [4 + 2] annulation of barbiturate-derived alkenes with allenoates. With the use of this tool, various spirobarbiturate-cyclohexenes are obtained in good to excellent yields with excellent diastereo- and enantioselectivities. A wide range of α-substituted allenoates and barbiturate-derived alkenes were tolerated. PMID:26937706

  12. IDENTIFICATION AND MANAGEMENT OF ALCOHOL WITHDRAWAL SYNDROME

    PubMed Central

    Mirijello, Antonio; D’Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni

    2016-01-01

    Symptoms of alcohol withdrawal syndrome may develop within 6–24 hours after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for alcohol withdrawal syndrome is represented by benzodiazepines. Among them, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as alpha2-agonists (clonidine and dexmetedomidine) and beta-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptics can help control hallucinations. Finally, other medications for the treatment for alcohol withdrawal syndrome have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin, and topiramate. The usefulness of these agents will be discussed in the text. PMID:25666543

  13. Electrophysiological and metabolic effects of a convulsant barbiturate on dissociated mouse primary sensory neurons.

    PubMed Central

    Pearce, R J; Duchen, M R

    1995-01-01

    1. The convulsant barbiturate 5-(2-cyclohexylidene-ethyl)-5-ethyl barbituric acid (CHEB) depolarizes dorsal root ganglion (DRG) neurons. We have applied microfluorimetric and whole-cell patch clamp techniques to investigate the mechanisms underlying this response in freshly dissociated mouse DRG cells. 2. Application of CHEB (2-200 microM) raised cytosolic calcium concentration ([Ca2+]i) rapidly and reversibly in 55% of eighty-three neurons tested. This population did not correlate with other classifications of sensory neurons based on either cell size or the expression of membrane currents. 3. The response was dependent on external calcium and was reduced by 81 +/- 22% by Ruthenium Red. A rise in [Ca2+]i was still seen with the membrane potential clamped at -70 mV, excluding membrane depolarization and activation of voltage-dependent Ca2+ channels as the principal mechanism for the response. 4. The rise in [Ca2+]i was associated with an increase in membrane conductance and a current, ICHEB, which was inward at -70 mV. Both the rise in [Ca2+]i and the current showed 'run-down' under whole-cell recording conditions. When K+ conductances were blocked, the reversal potential of ICHEB was close to 0 mV. This was independent of the Cl- reversal potential, suggesting that ICHEB is carried as a non-specific cation current. 5. In contrast to the change in [Ca2+]i, ICHEB was not dependent on external Ca2+ and the current was still seen when [Ca2+]i as strongly buffered by the pipette filling solution. These data suggest that CHEB opens a non-selective cation channel permeant to Ca2+, raising [Ca2+]i and further depolarizing the cell membrane potential. The exact nature of this conductance remains unknown. These actions could readily account for the convulsant actions of the drug, depolarizing neurons and increasing transmitter release. 6. It was also noted that CHEB increases autofluorescence derived from mitochondrial NAD(P)H. Further examination of this phenomenon using

  14. Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.

    PubMed

    Plessinger, M A

    1998-03-01

    Based on findings in humans and the confirmation of prenatal exposures in animals, amphetamines and methamphetamines increase the risk of an adverse outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal growth reduction deficits that have been seen in infants exposed to amphetamines during pregnancy have all been reproduced in animal studies involving prenatal exposures to amphetamines. The differential effects of amphetamines between genetic strains of mice and between species demonstrate that pharmacokinetics and the genetic disposition of the mother and developing embryo can have an enormous influence on enhancing or reducing these potential risks. The effects of prenatal exposure to amphetamines in producing altered behavior in humans appear less compelling when one considers other confounding variables of human environment, genetics, and polydrug abuse. In view of the animal data concerning altered behavior and learning tasks in comparison with learning deficits observed in humans, the influence of the confounding variables in humans may serve to increase the sensitivity of the developing embryo/fetus to prenatal exposure to amphetamines. These factors and others may predispose the developing conceptus to the damaging effects of amphetamines by actually lowering the threshold of susceptibility at the sites where damage occurs. Knowledge of the effects of prenatal exposure of the fetus and the mother to designer amphetamines is lacking. Based on the few studies in which designer drugs have been examined in animal models, more questions are raised than answered. Possible reasons why no malformations or significant fetal effects were found in the study by St. Omer include the genetic strain of rat used, the conservative exposure profile, or the fact that the placenta metabolized MDMA before reaching the embryo. These questions underscore the need for further investigations concerning the prenatal exposure effects of designer compounds and

  15. Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.

    PubMed

    Plessinger, M A

    1998-03-01

    Based on findings in humans and the confirmation of prenatal exposures in animals, amphetamines and methamphetamines increase the risk of an adverse outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal growth reduction deficits that have been seen in infants exposed to amphetamines during pregnancy have all been reproduced in animal studies involving prenatal exposures to amphetamines. The differential effects of amphetamines between genetic strains of mice and between species demonstrate that pharmacokinetics and the genetic disposition of the mother and developing embryo can have an enormous influence on enhancing or reducing these potential risks. The effects of prenatal exposure to amphetamines in producing altered behavior in humans appear less compelling when one considers other confounding variables of human environment, genetics, and polydrug abuse. In view of the animal data concerning altered behavior and learning tasks in comparison with learning deficits observed in humans, the influence of the confounding variables in humans may serve to increase the sensitivity of the developing embryo/fetus to prenatal exposure to amphetamines. These factors and others may predispose the developing conceptus to the damaging effects of amphetamines by actually lowering the threshold of susceptibility at the sites where damage occurs. Knowledge of the effects of prenatal exposure of the fetus and the mother to designer amphetamines is lacking. Based on the few studies in which designer drugs have been examined in animal models, more questions are raised than answered. Possible reasons why no malformations or significant fetal effects were found in the study by St. Omer include the genetic strain of rat used, the conservative exposure profile, or the fact that the placenta metabolized MDMA before reaching the embryo. These questions underscore the need for further investigations concerning the prenatal exposure effects of designer compounds and

  16. Competition between hydrocarbon and barbiturate for spectral binding to hepatic cytochrome P-450

    SciTech Connect

    Backes, W.L.; Means, M.; Canady, W.J.

    1984-08-25

    The substrates hexobarbital and ethylbenzene have been shown to compete for the spectral binding site of phenobarbital-induced rat hepatic microsomal cytochrome P-450. Over the concentration ranges studied, there is no change in the availability of the enzyme as a result of substrate addition; the difference in ..delta..Abs/sub max/ apparently being due to varying abilities of different substrates to bring about a spin shift in the enzyme. Evidence is presented to indicate that differences between enzymes from untreated male rats and phenobarbital-treated male rats are attributable to differences in the enzyme itself and not to changes in the nature of the membrane brought about by phenobarbital administration, at least insofar as heat entropy compensation is concerned. The enthalpy-entropy compensation observed in the binding of a homologous series of barbiturates to the microsomal membrane as determined from the membrane concentration dependence of their binding constants is shown to agree surprisingly well with the direct determination performed by Sitar and Mannering.

  17. Amphetamines and pH-shift agents for brain imaging

    SciTech Connect

    Biersack, H.J.; Winkler, C.

    1986-01-01

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

  18. Amphetamine Containing Dietary Supplements and Acute Myocardial Infarction

    PubMed Central

    Hritani, Abdulwahab; Antoun, Patrick

    2016-01-01

    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. PMID:27516911

  19. Amphetamine Containing Dietary Supplements and Acute Myocardial Infarction.

    PubMed

    Perez-Downes, Julio; Hritani, Abdulwahab; Baldeo, Candice; Antoun, Patrick

    2016-01-01

    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. PMID:27516911

  20. Amphetamine discrimination as a test for anti-parkinsonism drugs.

    PubMed

    Schechter, M D

    1977-07-01

    Rats were trained and tested on a two-lever discrimination task based upon the presence or absence of 0.8 mg/kg d-amphetamine. After 80% criterion performance was attained, dopaminergic drugs reported to be effective in the treatment of Parkinson's disease were tested to investigate their ability to produce d-amphetamine-like responding. Amantidine (50 mg/kg), apomorphine (2.5 mg/kg), n-propylnoraporphine (0.1, 0.2 and 1.0 mg/kg), and piribedil (25 mg/kg) were all observed to produce d-amphetamine-appropriate responding. These results indicate that discriminative behavior controlled by d-amphetamine is mediated by central dopaminergic systems and the use of this technique in the evaluation of potential anti-Parkinsonism drugs is discussed. PMID:885158

  1. Schedule-induced polydipsia experience decreases locomotor response to amphetamine.

    PubMed

    Tazi, A; Dantzer, R; Le Moal, M

    1988-04-01

    To investigate the influence of schedule-induced polydipsia (SIP) on central dopaminergic systems, rats trained in a SIP procedure were challenged with the psychostimulant and dopaminergic agonist, D-amphetamine. In a first experiment, rats that had access to water and developed SIP (SIP-positive) displayed a lower response to amphetamine than rats that had access to water but did not develop SIP (SIP-negative) and rats that had no access to water. There was no difference in the spontaneous activity of these different groups of animals. In a second experiment, SIP-positive rats displayed the same reduced response to amphetamine following only 10 min of SIP drinking. In addition, SIP-positive rats that were tested without access to water during the SIP test displayed an increased locomotor activity both after saline and amphetamine treatments. These results suggest that SIP has stress-reducing properties. PMID:3370459

  2. Amphetamine-related ischemic colitis causing gastrointestinal bleeding

    PubMed Central

    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

  3. Modulation of the locomotor response to amphetamine by corticosterone.

    PubMed

    Cador, M; Dulluc, J; Mormède, P

    1993-10-01

    In the present experiments, we investigated the influence of chronic modifications of circulating levels of corticosterone on the locomotor response to amphetamine. Different groups of rats were adrenalectomized and implanted subcutaneously with pellets releasing different amounts of corticosterone (0-200 mg). A wide range of corticosterone concentrations was reached in order to saturate selectively either the type I (mineralocorticoid) or the type II (glucocorticoid) corticosteroid receptors. The locomotor response to d-amphetamine (1.5 mg/kg) was studied 10-14 days later. We found that adrenalectomy reduced the response to d-amphetamine by 33% and that a normal response was restored with pellets releasing physiological concentrations of corticosterone (50-mg pellets), and was potentiated in animals with pellets releasing high amounts of corticosterone mimicking chronic stress situations (200-mg pellets). The correlation between plasma corticosterone concentration, locomotor activity following d-amphetamine and thymus weight, which is a reliable indicator of glucocorticoid action, shows that the influence of the locomotor response to d-amphetamine administration is likely to be mediated via a type II receptor. Since the locomotor activating effect of peripheral administration of d-amphetamine has been shown to depend on the integrity of the dopaminergic innervation of the nucleus accumbens, the effect of d-amphetamine at different doses (0, 1, 3, 10 micrograms/microliter) injected directly into the nucleus accumbens was studied. The results demonstrated that removing the circulating corticosterone induced a similar decrease of the locomotor activity elicited by d-amphetamine injection in the nucleus accumbens. This response was restored in animals with the 50- and 200-mg pellets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8284048

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

    PubMed

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

    2016-09-01

    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. PMID:27513635

  5. Alcoholism and Alcohol Abuse

    MedlinePlus

    ... This means that their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or ... brain, and other organs. Drinking during pregnancy can harm your baby. Alcohol also increases the risk of ...

  6. Amphetamine activates an amine-gated chloride channel to generate behavioral effects in Caenorhabditis elegans.

    PubMed

    Safratowich, Bryan D; Lor, Chee; Bianchi, Laura; Carvelli, Lucia

    2013-07-26

    Amphetamine is a highly addictive psychostimulant, which is thought to generate its effects by promoting release of dopamine through reverse activation of dopamine transporters. However, some amphetamine-mediated behaviors persist in dopamine transporter knock-out animals, suggesting the existence of alternative amphetamine targets. Here we demonstrate the identification of a novel amphetamine target by showing that in Caenorhabditis elegans, a large fraction of the behavioral effects of amphetamine is mediated through activation of the amine-gated chloride channel, LGC-55. These findings bring to light alternative pathways engaged by amphetamine, and urge rethinking of the molecular mechanisms underlying the effects of this highly-addictive psychostimulant.

  7. Stimulant ADHD Medications -- Methylphenidate and Amphetamines

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... Medicine Abuse Electronic Cigarettes (e-Cigarettes) Fentanyl Hallucinogens Heroin Inhalants Is Marijuana Medicine? Marijuana MDMA (Ecstasy/Molly) ...

  8. Influence of hypothermia, barbiturate therapy, and intracranial pressure monitoring on morbidity and mortality after near-drowning.

    PubMed

    Bohn, D J; Biggar, W D; Smith, C R; Conn, A W; Barker, G A

    1986-06-01

    We retrospectively evaluated the clinical and pathologic effects of hypothermia and high-dose barbiturate therapy on hypoxic/ischemic cerebral injury after near-drowning in children. Of 40 near-drowned patients admitted to the ICU, 13 died, seven had permanent cerebral damage, and 20 survived. Twenty-four patients (group 1) were treated with a regime of hyperventilation, hypothermia, and high-dose phenobarbitone while intracranial pressure (ICP) was continuously monitored. Of ten who died in this group, three were diagnosed as having cerebral death shortly after admission; autopsy revealed severe cerebral edema with herniation. The remaining seven nonsurvivors had severe cerebral hypoxia without raised ICP and had the features of severe adult respiratory distress syndrome and hypoxic/ischemic damage to other organs. Six of these seven patients developed septicemia which was invariably associated with a profound neutropenia. Sixteen patients (group 2) were treated with a similar protocol but without hypothermia. Three of these patients died but only one developed septicemia. Neutropenia after resuscitation from near-drowning seemed to indicate a poor prognosis; the mean polymorphonuclear leukocyte count in nonsurvivors (1.9 +/- 0.5 X 10(9) cell/L) was significantly (p less than .01) lower than that in survivors (6.4 +/- 1.1 X 10(9) cell/L). Hypothermia was associated with a decreased number of circulating PMNs but did not increase the number of neurologically intact survivors. Similarly, although barbiturates may control ICP, their use did not improve outcome. Because severe cerebral edema and herniation after near-drowning is usually associated with irreversible brain damage, measures to control brain swelling such as hypothermia and barbiturates will be of little benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Prefrontal cortical dopamine transmission is decreased in alcoholism

    PubMed Central

    Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L.; Douaihy, Antoine B.; Frankle, W. Gordon

    2014-01-01

    Objective Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such working memory, attention, inhibitory control and risk/reward decisions--all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies in alcoholics that have demonstrated less dopamine in the striatum, we hypothesized decreased dopamine transmission in the prefrontal cortex in alcoholism. To test this hypothesis, we used amphetamine and [11C]FLB 457 positron emission tomography (PET) to measure cortical dopamine transmission in a group of 21 recently abstinent alcoholics and matched healthy controls. Methods [11C]FLB 457 binding potential (BPND) was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg−1 of d-amphetamine. Results Amphetamine-induced displacement of [11C]FLB 457 binding potential (Δ BPND) was significantly smaller in the cortical regions in alcoholics compared to healthy controls. Cortical regions that demonstrated lower dopamine transmission in alcoholics included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex and medial temporal lobe. Conclusions The results of this study for the first time unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism. PMID:24874293

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2012-10-01

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

  13. Terahertz spectroscopic investigation of methylenedioxy amphetamine

    NASA Astrophysics Data System (ADS)

    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.

  14. Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond

    PubMed Central

    Sachdeva, Ankur; Chandra, Mina

    2015-01-01

    Alcohol dependence is an increasing and pervasive problem. Alcohol withdrawal symptoms are a part of alcohol dependence syndrome and are commonly encountered in general hospital settings, in most of the departments. Alcohol withdrawal syndrome ranges from mild to severe. The severe complicated alcohol withdrawal may present with hallucinations, seizures or delirium tremens. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal, and are considered the gold standard. Others, such as anticonvulsants, barbiturates, adrenergic drugs, and GABA agonists have been tried and have evidence. Supportive care and use of vitamins is essential in the management. Symptom triggered regime is favoured over fixed tapering dose regime, although monitoring through scales is cumbersome. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on ‘Alcohol withdrawal syndrome’ in humans during the last 10 years. A total of 1182 articles came up. Articles not relevant to clinical utility and management were excluded based on the titles and abstract available. Full text articles, meta-analyses, systematic reviews and randomized controlled trials were obtained from this list and were considered for review. PMID:26500991

  15. African American Female Basketball Players: An Examination of Alcohol and Drug Behaviors.

    ERIC Educational Resources Information Center

    Bower, Beverly L.; Martin, Malissa

    1999-01-01

    Investigated alcohol and drug use by African-American female college basketball players. Surveys indicated that three-quarters of the women consumed alcohol. Nearly half had engaged in binge drinking. Very few reported using weight-loss or tobacco products. There were no reports of amphetamine or anabolic steroid use. Respondents appeared aware of…

  16. Synthesis of barbituric acid containing nucleotides and their implications for the origin of primitive informational polymers.

    PubMed

    Mungi, Chaitanya V; Singh, Sachin Kumar; Chugh, Jeetender; Rajamani, Sudha

    2016-07-27

    Given that all processes in modern biology are encoded and orchestrated by polymers, the origin of informational molecules had to be a crucial and significant step in the origin of life on Earth. An important molecule in this context is RNA that is thought to have allowed the transition from chemistry to biology. However, the RNA molecule is comprised of intramolecular bonds which are prone to hydrolysis, especially so under the harsh conditions of the early Earth. Furthermore, the formation of nucleotides with extant bases and their subsequent polymerization have both been problematic, to say the least. Alternate heterocycles, in contrast, have resulted in nucleosides in higher yields, suggesting a viable and prebiotically relevant solution to the longstanding "nucleoside problem". In the present study, we have synthesized a nucleotide using ribose 5'-monophosphate (rMP) and barbituric acid (BA), as the base analog, using dry-heating conditions that are thought to be prevalent in several regimes of the early Earth. Polymerization of the resultant monomers, i.e. BA-nucleotides, was also observed when dehydration-rehydration cycles were carried out at low pH and high temperature. The resulting RNA-like oligomers have intact bases unlike in reactions that were carried out with canonical nucleotides, which resulted in abasic sites under acidic conditions due to cleavage of the N-glycosidic linkages. Furthermore, the incorporation of BA directly into preformed sugar-phosphate backbones was also observed when rMP oligomers were subjected to heating with BA. The results from our aforementioned experiments provide preliminary evidence that BA could have been a putative precursor of modern nucleobases, which could have been incorporated into primitive informational polymers that predated the molecules of an RNA world. Moreover, they also highlight that the prebiotic soup, which would have been replete with alternate heterocycles, could have allowed the sampling of other

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

    PubMed

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

    2013-10-01

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

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

    PubMed

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

    2013-10-01

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

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

    PubMed Central

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

    2013-01-01

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

  20. Uptake of barbituric acid derivatives in small intestinal brush border membrane vesicles from retinyl palmitate-treated rats.

    PubMed

    Tanii, H; Horie, T

    2000-08-01

    Brush border membrane was prepared from the small intestinal (jejunum) cells along the crypt-villus axis. The fluorescence spectra of 1,8-anilinonaphthalene sulfonic acid and the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene were measured in the brush border membrane vesicle suspension. The hydrophobicity of brush border membrane was found to be in the order villus tip >mid villus >lower villus. The fluidity of brush border membrane was in the order villus tip barbituric acid derivatives by brush border membrane vesicles was well correlated with their partition coefficients (isopentyl acetate/water). No significant difference was observed between the uptake of hexobarbital by brush border membrane vesicles from the villus tip and lower villus. When retinyl palmitate was administered to rats, the fluidity of brush border membrane was found to be higher in the retinyl palmitate-treated rats than in the control rats. However, no significant difference in the uptake of hexobarbital by brush border membrane vesicles was observed between the retinyl palmitate-administered rats and the control rats. Thus, the retinyl palmitate treatment seems unlikely to affect the passively transported ligands like barbituric acid derivatives in brush border membrane vesicles. PMID:10989945

  1. Amphetamine and methamphetamine have a direct and differential effect on BV2 microglia cells.

    PubMed

    Shanks, R A; Anderson, J R; Taylor, J R; Lloyd, S A

    2012-12-01

    A comparative analysis of the direct effects of amphetamine and methamphetamine exposure on BV2 microglia cells in the presence and absence of cellular debris was performed. A significant dose-dependent and treatment-dependent effect of amphetamine and methamphetamine on BV2 cells was demonstrated: methamphetamine, but not amphetamine, inhibited phagocytosis, and a differential regulation of cytokines was observed in response to amphetamine and methamphetamine.

  2. Argon prevents the development of locomotor sensitization to amphetamine and amphetamine-induced changes in mu opioid receptor in the nucleus accumbens.

    PubMed

    David, Hélène N; Dhilly, Martine; Poisnel, Géraldine; Degoulet, Mickael; Meckler, Cédric; Vallée, Nicolas; Blatteau, Jean-Éric; Risso, Jean-Jacques; Lemaire, Marc; Debruyne, Danièle; Abraini, Jacques H

    2014-01-01

    Systemic administration of γ-amino-butyric acid type A (GABA-A) and benzodiazepine receptor agonists has been reported to block the development of locomotor sensitization to amphetamine. Here, we investigated whether the non-anesthetic noble gas argon, shown to possess agonistic properties at these receptors, may block the acquisition of amphetamine-induced locomotor sensitization and mu opioid receptor activation in the nucleus accumbens. Rats were pretreated with saline solution or amphetamine (1 mg/kg) from day 1 to day 3 and then exposed, immediately after injection of amphetamine, to medicinal air or argon at 75 vol% (with the remainder being oxygen). After a 3-day period of withdrawal, rats were challenged with amphetamine on day 7. Rats pretreated with amphetamine and argon had lower locomotor activity (U = 5, P < 0.005) and mu opioid receptor activity in the nucleus accumbens (U = 0, P < 0.001) than rats pretreated with amphetamine and air. In contrast, argon had effect on locomotor and mu receptor activity neither in rats pretreated with saline and challenged with amphetamine (acute amphetamine) nor in rats pretreated and challenged with saline solution (controls). These results indicate that argon inhibits the development of both locomotor sensitization and mu opioid receptor activation induced by repeated administration of amphetamine.

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

    PubMed Central

    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

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

    PubMed

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

    2015-01-01

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

  5. Corticosterone levels determine individual vulnerability to amphetamine self-administration.

    PubMed Central

    Piazza, P V; Maccari, S; Deminière, J M; Le Moal, M; Mormède, P; Simon, H

    1991-01-01

    Individual vulnerability to the reinforcing properties of drugs appears to be an essential characteristic predisposing humans to addiction. In animals, a greater behavioral reactivity to a mild stress, such as exposure to a novel environment, is an index of the vulnerability to acquire amphetamine self-administration. Biological responses to stress as well as behavioral reactivity may predict such a vulnerability. In the present study, rats with a longer duration of corticosterone secretion after exposure to novelty showed facilitation of acquisition of amphetamine self-administration. Furthermore, corticosterone administration in nonpredisposed individuals increased the reinforcing value of the drug and facilitated the acquisition of amphetamine self-administration. These results indicate that the stress-related activity of the hypothalamic-pituitary-adrenal axis may play a role in the pathogenesis of psychostimulant addiction. PMID:2006148

  6. Punished behavior: increases in responding after d-amphetamine.

    PubMed

    McKearney, J W; Barrett, J E

    1975-01-01

    Responding maintained in squirrel monkeys under a 10-min fixed-interval schedule of food presentation was suppressed by presenting a shock after every 30th response (punishment). During alternate 10-min periods of the same experimental session, but in the presence of a different discriminative stimulus, responding either had no effect (extinction) or postponed delivery of an electric shock (avoidance). During sessions when the avoidance schedule was not in effect, d-amphetamine sulfate decreased punished responding. When the avoidance schedule was present during alternate 10-min periods, however, d-amphetamine (0.01 minus 0.56 mg/kg, i.m.) markedly increased responding during punishment components. Increases in responding during avoidance components were also evident. The effects of d-amphetamine on punished responding depend on the context in which that responding occurs. PMID:804701

  7. Reduced ethanol consumption and preference in cocaine- and amphetamine-regulated transcript (CART) knockout mice.

    PubMed

    Salinas, Armando G; Nguyen, Chinh T Q; Ahmadi-Tehrani, Dara; Morrisett, Richard A

    2014-03-01

    Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide implicated in addiction to drugs of abuse. Several studies have characterized the role of CART in addiction to psychostimulants, but few have examined the role of CART in alcohol use disorders including alcoholism. The current study utilized a CART knockout (KO) mouse model to investigate the role of CART in ethanol appetitive behaviors. A two-bottle choice, unlimited-access paradigm was used to compare ethanol appetitive behaviors between CART wild type (WT) and KO mice. The mice were presented with an ethanol solution (3%-21%) and water, each concentration for 4 days, and their consumption was measured daily. Consumption of quinine (bitter) and saccharin (sweet) solutions was measured following the ethanol preference tests. In addition, ethanol metabolism rates and ethanol sensitivity were compared between genotypes. CART KO mice consumed and preferred ethanol less than their WT counterparts in both sexes. This genotype effect could not be attributed to differences in bitter or sweet taste perception or ethanol metabolism rates. There was also no difference in ethanol sensitivity in male mice; however, CART KO female mice showed a greater ethanol sensitivity than the WT females. Taken together, these data demonstrate a role for CART in ethanol appetitive behaviors and as a possible therapeutic drug target for alcoholism and abstinence enhancement.

  8. Modafinil treatment of amphetamine abuse in adult ADHD.

    PubMed

    Mann, N; Bitsios, P

    2009-06-01

    Substance abuse is a frequent co-morbid condition of adult attention deficit hyperactivity disorder (ADHD). Treatment with conventional psychostimulants in adult ADHD with co-morbid stimulant abuse may be problematic. In this study, we report the case of a patient with adult ADHD with co-morbid amphetamine abuse who was treated successfully with the non-stimulant alertness-promoting drug modafinil. The drug resolved both the inattention/hyperactivity symptoms as well as the amphetamine abuse. Modafinil may be a suitable candidate treatment for adults with ADHD and stimulant abuse.

  9. [Vibration studies of amphetamine and methamphetamine by micro Raman].

    PubMed

    Zhao, J; Chen, D; Zhang, P; Lu, F; Xie, H; Li, H

    1999-10-01

    For the first time, we obtained and investigated the Raman spectra of amphetamine and methamphetamine by micro Raman with incidence excitation light 514.5 nm under the ambient environment. According to the fact that both molecules belong to single substituted benzene which has the symmetry of Cy2v, the attribution of Raman vibration modes in amphetamine and methamphetamine molecules was carried out by studying the spectral lines in the two spectra. The Raman line that only appeared in methamphetamine but could not be seen in any other drugs we have investigated was most possibly attributed to the stretching vibration between C-N(+)-C.

  10. Differential interactions of desipramine with amphetamine and methamphetamine: evidence that amphetamine releases dopamine from noradrenergic neurons in the medial prefrontal cortex.

    PubMed

    Shoblock, James R; Maisonneuve, Isabelle M; Glick, Stanley D

    2004-07-01

    Amphetamine is more effective than methamphetamine at raising dopamine levels in the prefrontal cortex. The current study tested the hypothesis that norepinephrine transporters are involved in this difference. Using microdialysis, dopamine, norepinephrine, and serotonin were measured in the rat prefrontal cortex after administration of methamphetamine or amphetamine, with and without perfusion of desipramine. Amphetamine raised norepinephrine levels more than methamphetamine did. Desipramine raised dopamine and serotonin levels but did not alter metabolite levels. Desipramine attenuated the increase in dopamine by amphetamine while increasing the dopamine released by methamphetamine. These data suggest that methamphetamine and amphetamine differ in altering prefrontal cortical dopamine levels and in interacting with norepinephrine transporters. It is proposed that amphetamine releases dopamine in the prefrontal cortex primarily through norepinephrine transporters, whereas methamphetamine interacts minimally with norepinephrine transporters.

  11. HYPOTHALAMIC OREXINE SYSTEM ACCELERATES REGULATION OF SLEEP HOMEOSTASIS AND SLEEP-WAKEFULNESS CYCLE RECOVERY FROM BARBITURATE ANESTHESIA-INDUCED ARTIFICIAL SLEEP.

    PubMed

    Nachkebia, N; Maglakelidze, N; Chijavadze, E; Chkhartishvili, E; Babilodze, M

    2015-12-01

    The work was aimed for the ascertainment of following question - whether Orexin-containing neurons of dorsal and lateral hypothalamus and brain Orexinergic system in general are those cellular targets which can accelerate recovery of disturbed sleep homeostasis and restoration of sleep-wakefulness cycle behavioral states from barbiturate anesthesia-induced artificial sleep. Investigation was carried out on 18 wild type white rats (weight 200-250gr). Different doses of Nembutal Sodium were used for the initiation of deep anesthesia. 30 min after barbiturate anesthesia induced artificial sleep serial electrical stimulations of dorsal or lateral hypothalamus were started. Stimulation period lasted for 1 hour with the 5 min intervals between subsequent stimulations applied by turn to the left and right side hypothalamic parts. EEG registration of cortical and hippocampal electrical activity was started 10 min after intra-peritoneal administration of Nembutal Sodium and continued continuously during 72 hour. According to obtained new evidences, serial electrical stimulations of dorsal and lateral hypothalamic Orexin-containing neurons significantly accelerate recovery of wakefulness, sleep homeostasis, disturbed because of barbiturate anesthesia induced artificial sleep and different behavioral states of sleep-wakefulness cycle. Hypothalamic Orexin-containing neurons can be considered as the cellular targets for regulating of sleep homeostasis through the acceleration of recovery of wakefulness, and SWC in general, from barbiturate anesthesia-induced deep sleep. PMID:26719553

  12. Evidence against the Bm1P1 protein as a positive transcription factor for barbiturate-mediated induction of cytochrome P450BM-1 in bacillus megaterium.

    PubMed

    Shaw, G C; Sung, C C; Liu, C H; Lin, C H

    1998-04-01

    The Bm1P1 protein was previously proposed to act as a positive transcription factor involved in barbiturate-mediated induction of cytochrome P450BM-1 in Bacillus megaterium. We now report that the bm1P1 gene encodes a protein of 217 amino acids, rather than the 98 amino acids as reported previously. In vitro gel shift assays indicate that the Bm1P1 protein did not interact with probes comprising the regulatory regions of the P450BM-1 gene. Moreover, disruption of the bm1P1 gene did not markedly affect barbiturate induction of P450BM-1 expression. A multicopy plasmid harboring only the P450BM-1 promoter region could increase expression of the chromosome-encoded P450BM-1. The level of expression is comparable with that shown by a multicopy plasmid harboring the P450BM-1 promoter region along with the bm1P1 gene. These results strongly suggest that the Bm1P1 protein is unlikely to act as a positive regulator for barbiturate induction of P450BM-1 expression. Finally, deletion of the Barbie box did not markedly diminish the effect of pentobarbital on expression of a reporter gene transcriptionally fused to the P450BM-1 promoter. This suggests that the Barbie box is unlikely to be a key element in barbiturate-mediated induction of P450BM-1. PMID:9525898

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

    PubMed

    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.

  14. Analyses Related to the Development of DSM-5 Criteria for Substance Use Related Disorders: 1. Toward Amphetamine, Cocaine and Prescription Drug Use Disorder Continua Using Item Response Theory

    PubMed Central

    Saha, Tulshi D.; Compton, Wilson M.; Chou, S. Patricia; Smith, Sharon; Ruan, W. June; Huang, Boji; Pickering, Roger P.; Grant, Bridget F.

    2011-01-01

    Background Prior research has demonstrated the dimensionality of alcohol, nicotine and cannabis use disorders criteria. The purpose of this study was to examine the unidimensionality of DSM-IV cocaine, amphetamine and prescription drug abuse and dependence criteria and to determine the impact of elimination of the legal problems criterion on the information value of the aggregate criteria. Methods Factor analyses and Item Response Theory (IRT) analyses were used to explore the unidimensionality and psychometric properties of the illicit drug use criteria using a large representative sample of the U.S. population. Results All illicit drug abuse and dependence criteria formed unidimensional latent traits. For amphetamines, cocaine, sedatives, tranquilizers and opioids, IRT models fit better for models without legal problems criterion than models with legal problems criterion and there were no differences in the information value of the IRT models with and without the legal problems criterion, supporting the elimination of that criterion. Conclusion Consistent with findings for alcohol, nicotine and cannabis, amphetamine, cocaine, sedative, tranquilizer and opioid abuse and dependence criteria reflect underlying unitary dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the American Psychiatric Association’s DSM-5 Substance and Related Disorders Workgroup. PMID:21963414

  15. AMPA-receptors are involved in the expression of amphetamine-induced behavioural sensitisation, but not in the expression of amphetamine-induced conditioned activity in mice.

    PubMed

    Mead, A N; Stephens, D N

    1998-09-01

    We investigated the role of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX) in the expression of amphetamine-induced behavioural sensitisation and amphetamine-induced conditioned activity in mice. Repeated weekly administration of amphetamine (0.375 mg/kg) for 7 weeks led to an increased locomotor response when challenged with amphetamine 1 week later. NBQX attenuated this increased response at doses (3 and 30 mg/kg) which had no effect on the acute locomotor response to amphetamine. In a separate experiment, mice given amphetamine (1 mg/kg) in a distinctive environment, showed an increased locomotor response within this environment following a subsequent saline administration. NBQX (5-20 mg/kg) had no effect on the expression of this conditioned response. These results suggest that AMPA receptors are involved in the expression of amphetamine-induced behavioural sensitisation in mice, and that this involvement is limited to either the neurobiological effects of amphetamine or the effects of amphetamine on conditioned associations, rather than drug environment conditioned associations.

  16. The effects of amphetamine on body weight and energy expenditure.

    PubMed

    Jones, J R; Caul, W F; Hill, J O

    1992-03-01

    Although there is evidence suggesting that, in addition to suppressing food consumption, amphetamine reduces body weight by increasing energy expenditure, there is little consistency among the few studies examining that factor. In this experiment, the effect of amphetamine on daily energy consumption, within-day body weights, and hourly measures of metabolic rate (MR) and respiration quotient (RQ) were assessed. Daytime drug injections decreased total energy consumption, produced biphasic changes over time in MR, and persistently lowered RQ values. In contrast, nighttime injections of drug had little effect on energy consumption and MR but did reduce RQ for the first 4 postinjection hours. These effects show that amphetamine effects interact with the circadian organization of behavior and suggest that rodent studies of anorectic agents have more relevance for humans if drugs are given during the night, when rats are normally awake and eating. From this study, it seems clear that amphetamine reduces body weight by altering metabolic rate and fat metabolism in rats when the drug is given during the day.

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed

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

    2016-06-30

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

  19. Taste-potentiated odor aversion learning based on amphetamine.

    PubMed

    Bryant, P A; Boakes, R A; McGregor, I S

    1993-08-01

    This study sought to determine whether a taste can potentiate a conditioned odor aversion based on amphetamine as well as those based on lithium. A taste-potentiated odor aversion (TPOA) based on lithium was obtained in Experiment 1 only with a low concentration of an almond odor. This concentration was used in Experiment 2 where the taste, 0.1% saccharin, potentiated an odor aversion based on 1 mg/kg d-amphetamine. This was replicated in Experiment 3 where potentiation was found with doses of both 1 and 3 mg/kg amphetamine, and no effect of dose was detected. It was concluded that TPOA learning is not restricted to drugs such as lithium that produce conditioned unpalatability as well as conditioned aversions to a taste, because amphetamine does not produce conditioned unpalatability at the doses used here. Furthermore, because in Experiment 3 postconditioning extinction of the saccharin aversion removed the potentiation effect, it appears that this form of TPOA may depend on an association between the odor and taste, as proposed by within-compound theory.

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Small volume liquid extraction of amphetamines in saliva.

    PubMed

    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 <100 microL solvent was used instead of several milliliters in LPE. Conditions such as types and volumes of organic solvent used in the extraction and concentrations of target analytes in aqueous samples were examined. Results showed that small volume liquid extraction had an enrichment effect on the analytes. After extraction, the organic phase was either directly drawn out for GC analysis, or partially transferred to another vial for derivatization. Detection limits were less than 5 ng/mL in saliva using GC/MS-SIM after derivatization. RSD (of peak area ratios) was less than 15% at all drug concentrations. The method was used in the analyses of saliva collected from amphetamine abusers, and was proven to be practical for detecting trace amounts of amphetamines in saliva.

  2. The neurotoxicity of amphetamines during the adolescent period.

    PubMed

    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. PMID:25482046

  3. Voltammetric sensor for barbituric acid based on a sol-gel derivated molecularly imprinted polymer brush grafted to graphite electrode.

    PubMed

    Patel, Amit Kumar; Sharma, Piyush Sindhu; Prasad, Bhim Bali

    2009-04-17

    A voltammetric sensor based on a molecularly imprinted polymer (MIP) brush grafted to sol-gel film on graphite electrode is reported for the selective and sensitive analysis of barbituric acid (BA) in aqueous, blood plasma, and urine samples. The modified electrode was preanodised at +1.6 V (vs. saturated calomel electrode), where encapsulated BA involved hydrophobically induced hydrogen bondings, in MIP cavities exposed at the film/solution interface, at pH 7.0. Scanning electron microscopy (SEM) was employed to characterise the surface morphology of the resultant imprinted film of MIP brush. The differential pulse, cathodic stripping voltammetry (DPCSV) technique was employed to investigate the binding performance of the sol-gel-modified imprinted polymer brush, which yielded a linear response in the range of 4.95-100.00 microg mL(-1) of BA with a detection limit of 1.6 microg mL(-1) (S/N=3). PMID:19135515

  4. Response map properties of units in the dorsal cochlear nucleus of barbiturate-anesthetized gerbil (Meriones unguiculatus).

    PubMed

    Gdowski, G T; Voigt, H F

    1997-03-01

    The response map scheme introduced by Evans and Nelson (1973) and modified by others, including Davis et al. (1996) for use with gerbils, has been used primarily for classifying units recorded in the cochlear nucleus of unanesthetized decerebrate preparations. Units lacking spontaneous activity (SpAc) have been classified as either type I/III or type II units based on the relative strength of their responses to broad-band noise compared to their responses to best-frequency (BF) tones. The relative noise index (rho), a ratio of these responses after SpAc is subtracted out, provides a convenient measure of this relative strength. In this paper, responses of 320 units recorded in the dorsal cochlear nucleus (DCN) of barbiturate-anesthetized gerbils to short-duration BF tones and broad-band noise were recorded. Since 87.5% of these units lacked SpAc, their response maps resembled those of type II and type I/III units. Units were characterized by rho and the normalized slope (m) of a best line fit to the BF rate versus level plot starting from the sound level corresponding to the first inflection point of the rate curve (typically its maximum value or the start of its sloping saturation). The distributions of rho and m values do not form distinct clusters as they do for units in the decerebrate preparation. Thus, the criteria developed for classifying DCN units in the decerebrate preparation do not appear appropriate for units in the barbiturate-anesthetized preparation. Deposits of horseradish peroxidase were used to locate 52 units. Most of the low SpAc units, 56% with poor noise responses (5/9) and nearly 70% with strong noise responses (25/36), and nearly all of the high SpAc units (6/7), were located either within or below the fusiform cell layer. PMID:9083807

  5. Occurrence of a barbiturate-inducible catalytically self-sufficient 119,000 dalton cytochrome P-450 monooxygenase in bacilli.

    PubMed

    Fulco, A J; Ruettinger, R T

    1987-05-01

    In a recent publication (Narhi, L.O. and Fulco, A.J.[1986] J. Biol. Chem. 261, 7160-7169) we described the characterization of a catalytically self-sufficient 119,000 Dalton cytochrome P-450 fatty acid monooxygenase (P-450BM-3) induced by barbiturates in Bacillus megaterium ATCC 14581. We have now examined cell-free preparations from 12 distinct strains of B. megaterium and from one or two strains each of B. alvei, B. brevis, B. cereus, B. licheniformis, B. macerans, B. pumilis and B. subtilis for the presence of this inducible enzyme. Using Western blot analyses in combination with assays for fatty acid hydroxylase activity and cytochrome P-450, we were able to show that 11 of the 12 B. megaterium strains contained not only a strongly pentobarbital-inducible fatty acid monooxygenase identical to or polymorphic with P-450BM-3 but also significant levels of two smaller P-450 cytochromes that were the same as or similar to cytochromes P-450BM-1 and P-450BM-2 originally found in ATCC 14581. Unlike the 119,000 Dalton P-450, however, the two smaller P-450s were generally easily detectable in cultures grown to stationary phase in the absence of barbiturates and, with some exceptions, were not strongly induced by pentobarbital. None of the non-megaterium species of Bacillus tested exhibited significant levels of either fatty acid monooxygenase activity or cytochrome P-450. The one strain of B. megaterium that lacked inducible P-450BM-3 was also negative for BM-1 and BM-2. However, this strain (ATCC 13368) did contain a small but significant level of another P-450 cytochrome that others have identified as the oxygenase component of a steroid 15-beta-hydroxylase system. Our evidence suggests that the BM series of P-450 cytochromes is encoded by chromosomal (rather than by plasmid) DNA. PMID:3573977

  6. The metabolic fate of amphetamine in man and other species

    PubMed Central

    Dring, L. G.; Smith, R. L.; Williams, R. T.

    1970-01-01

    1. The fate of [14C]amphetamine in man, rhesus monkey, greyhound, rat, rabbit, mouse and guinea pig has been studied. 2. In three men receiving orally 5mg each (about 0.07mg/kg), about 90% of the 14C was excreted in the urine in 3–4 days. About 60–65% of the 14C was excreted in 1 day, 30% as unchanged drug, 21% as total benzoic acid and 3% as 4-hydroxyamphetamine. 3. In two rhesus monkeys (dose 0.66mg/kg), the metabolites excreted in 24h were similar to those in man except that there was little 4-hydroxyamphetamine. 4. In greyhounds receiving 5mg/kg intraperitoneally the metabolites were similar in amount to those in man. 5. Rabbits receiving 10mg/kg orally differed from all other species. They excreted little unchanged amphetamine (4% of dose) and 4-hydroxyamphetamine (6%). They excreted in 24h mainly benzoic acid (total 25%), an acid-labile precursor of 1-phenylpropan-2-one (benzyl methyl ketone) (22%) and conjugated 1-phenylpropan-2-ol (benzylmethylcarbinol) (7%). 6. Rats receiving 10mg/kg orally also differed from other species. The main metabolite (60% of dose) was conjugated 4-hydroxyamphetamine. Minor metabolites were amphetamine (13%), N-acetylamphetamine (2%), norephedrine (0.3%) and 4-hydroxynorephedrine (0.3%). 7. The guinea pig receiving 5mg/kg excreted only benzoic acid and its conjugates (62%) and amphetamine (22%). 8. The mouse receiving 10mg/kg excreted amphetamine (33%), 4-hydroxyamphetamine (14%) and benzoic acid and its conjugates (31%). 9. Experiments on the precursor of 1-phenylpropan-2-one occurring in rabbit urine suggest that it might be the enol sulphate of the ketone. A very small amount of the ketone (1–3%) was also found in human and greyhound urine after acid hydrolysis. PMID:4985156

  7. Medical Readings on Drug Abuse.

    ERIC Educational Resources Information Center

    Byrd, Oliver E.

    Summaries are presented of over 150 articles in the recent medical and psychiatric literature. Topics covered are: effects of drugs, tobacco, alcohol, drugs used in medicine, vapor sniffing, marijuana, barbiturates, tranquilizers, amphetamines, methamphetamine, lysergic acid diethylamide, other hallucinogens, heroin and the opiates, psychiatric…

  8. [Selected Readings for the Professional Working with Drug Related Problems.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison.

    A bibliography of selected readings compiled at the University of Wisconsin for the National Drug Education Training Program. These selected readings include information on narcotics, amphetamines, mescaline, psilogybin, hallucinogens, LSD, barbiturates, alcohol, and other stimulants. The intended user of this bibliography is the professional…

  9. Substance Use by Fourth-Year Students at 13 U.S. Medical Schools.

    ERIC Educational Resources Information Center

    Conard, Scott; And Others

    1988-01-01

    A study investigated drug use by fourth-year medical students in 13 schools and compared drug use patterns with those of an age- and sex-matched cohort. Medical students reported less use of marijuana, cocaine, cigarettes, LSD, barbiturates, and amphetamines, similar use of opiates, and slightly more use of tranquilizers and alcohol. (MSE)

  10. Amphetamine primes motivation to gamble and gambling-related semantic networks in problem gamblers.

    PubMed

    Zack, Martin; Poulos, Constantine X

    2004-01-01

    Previous research suggests that gambling can induce effects that closely resemble a psychostimulant drug effect. Modest doses of addictive drugs can prime motivation for drugs with similar properties. Together, these findings imply that a dose of a psychostimulant drug could prime motivation to gamble in problem gamblers. This study assessed priming effects of oral D-amphetamine (AMPH) (30 mg) in a within-subject, counter-balanced, placebo-controlled design in problem gamblers (n=10), comorbid gamblerdrinkers (n=6), problem drinkers (n=8), and healthy controls (n=12). Modified visual analog scales assessed addictive motivation and subjective effects. A modified rapid reading task assessed pharmacological activation of words from motivationally relevant and irrelevant semantic domains (Gambling, Alcohol, Positive Affect, Negative Affect, Neutral). AMPH increased self-reported motivation for gambling in problem gamblers. Severity of problem gambling predicted positive subjective effects of AMPH and motivation to gamble under the drug. There was little evidence that AMPH directly primed motivation for alcohol in problem drinkers. On the reading task, AMPH produced undifferentiated improvement in reading speed to all word classes in Nongamblers. By contrast, in the two problem gambler groups, AMPH improved reading speed to Gambling words while profoundly slowing reading speed to motivationally irrelevant Neutral words. The latter finding was interpreted as directly congruent with models, which contend that priming of addictive motivation involves a linked suppression of motivationally irrelevant stimuli. This study provides experimental evidence that psychostimulant-like neurochemical activation is an important component of gambling addiction.

  11. Alcohol and marijuana effects on ocular tracking.

    PubMed

    Flom, M C; Brown, B; Adams, A J; Jones, R T

    1976-12-01

    Experienced alcohol and marijuana users were instructed to track with their eyes a small spot that moved horizontally back and forth in pendular (sinusoidal) motion across a 7.5-degree field. The frequency of spot oscillation was gradually increased from 0.5 to 3.0 Hz in 40 sec. Eye movement recordings showed the frequency at which smooth tracking and, soon thereafter, saccadic tracking broke down. These smooth and saccadic cutoff frequencies were reduced after administration of alcohol, but not after marijuana or placebo. For low alcohol doses, smooth tracking was impaired and saccadic tracking was unaffected, much like an effect previously reported for barbiturates. Alcohol seems to affect smooth tracking by increasing the central processing time required to generate the appropriate eye movement. It affects saccadic tracking by slightly decreasing saccadic velocity and to a greater extent by increasing latency time, part of which may be devoted to central processing. The site of action of alcohol appears to be central to both the paramedian pontine reticular formation and the flocculus of the cerebellum.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Technical Reports Server (NTRS)

    Kohl, Randall Lee

    1986-01-01

    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, the efficacy of dexamethasone and metyrapone is tested 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 percent 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.

  14. Detection of levorotatory methamphetamine and levorotatory amphetamine in urine after ingestion of an overdose of selegiline.

    PubMed

    Fujita, Yuji; Takahashi, Katsuo; Takei, Masao; Niitsu, Hisae; Aoki, Yasuhiro; Onodera, Makoto; Fujino, Yasuhisa; Inoue, Yoshihiro; Endo, Shigeatsu

    2008-10-01

    In this study, we measured the urine concentrations of methamphetamine and amphetamine as metabolites of selegiline after ingestion of an overdose of selegiline. A patient who had developed Parkinson disease took selegiline in a suicide attempt. Analysis by gas chromatography-mass spectrometry (GC-MS) with trifluoroacetic acid-derivatization revealed the presence of methamphetamine and amphetamine in the patient's urine at concentrations of 0.62 microg/ml and 0.25 microg/ml, respectively. To determine the stereospecificity of the methamphetamine and amphetamine, a urine sample was analyzed by GC-MS after derivatization with N-(trifluoroacetyl)-l-prolyl chloride. The methamphetamine and amphetamine were levorotatory in form. The ratio of the methamphetamine to amphetamine concentration in the urine was 2.5. This value is consistent with other case reports of ingestion of selegiline, which suggests that the methamphetamine to amphetamine concentration ratio in urine is useful information for indicating use of selegiline.

  15. Low concentrations of methamphetamine detectable in urine in the presence of high concentrations of amphetamine.

    PubMed

    Jemionek, John F; Addison, Joseph; Past, Marilyn R

    2009-04-01

    Twenty-two urine specimens reported by military drug-testing laboratories for the presence of high concentrations of amphetamine only were subject to further analysis for the presence of methamphetamine. The 22 urine specimens had concentrations of amphetamine in the range of 28,028 to 241,142 ng/mL. The specimens were also assayed for the respective isomeric ratio of d (S) and l (R) amphetamine and methamphetamine. The results suggest that urine specimens containing high concentrations of amphetamine in which the urine concentration ratio of methamphetamine to amphetamine is less than 0.5% with similar isomeric distribution of d-(S) and l-(R) amphetamine and methamphetamine, respectively, may not necessarily indicate polydrug use.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Stress- and pharmacologically-induced behavioral sensitization increases vulnerability to acquisition of amphetamine self-administration.

    PubMed

    Piazza, P V; Deminiere, J M; le Moal, M; Simon, H

    1990-04-23

    Individual vulnerability to drug addiction may be an important factor in the prognosis of this pathological behavior in man. However, experimental investigations have largely neglected the psychobiological substrate of predisposition to addiction. In this study, we show using a self-administration (SA) acquisition paradigm that previous repeated exposure to a stressful experience (tail-pinch) or to amphetamine, increase the locomotor response to this drug (behavioral sensitization) and enhance vulnerability to acquire amphetamine SA. These results show that vulnerability to develop amphetamine SA may be influenced by stressful experiences, and that previous contact with the drug may enhance a predisposition to amphetamine-taking behavior. As tail-pinch and amphetamine sensitization affect both the dopamine (DA) neural system and the propensity to self-administer amphetamine (behavior also modulated by DA activity), stress may influence SA via an action on the DA system. PMID:2357527

  18. Effect of amphetamines on speech defects in the mentally retarded.

    PubMed

    FISH, C H; BOWLING, E

    1962-02-01

    In a double-blind study, 106 mentally retarded patients with speech defects were given 15 mg. of d-Amphetamine daily, or a placebo, for a three-month period. Speech defect types were: Stuttering, immature production, oral inaccuracy, lisp, psychotic, mongoloid, aphasia, deafness, and cleft palate. Only the stutterers showed obvious improvement in comparison with the placebo group. Three severe, long-term stutterers showed such dramatic improvement that their whole course in life has been changed. PMID:13893193

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

    PubMed Central

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

    2015-01-01

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

  20. Perseverative behaviour after amphetamine; dissociation of response tendency from reward association.

    PubMed

    Ridley, R M; Baker, H F; Haystead, T A

    1981-01-01

    Low doses of amphetamine were found to alter the ability of marmosets to take account of changes in reward values of object stimuli in a visual discrimination task. Under amphetamine, animals changed their motor responses and stimulus choice in order to preserve the acquired reward value or meaning of certain stimuli. These results suggest that the perseverative effect of amphetamine on behaviour is due to impaired cognitive flexibility rather than to an enhancement of motor habit.

  1. Differential sensitization to amphetamine and stress responsivity as a function of inherent laterality.

    PubMed

    LaHoste, G J; Mormède, P; Rivet, J M; Le Moal, M

    1988-06-21

    With repeated administrations, rodents become increasingly sensitive to the stimulant properties of amphetamine, a phenomenon termed sensitization. Rats differentiated on the basis of their preferred direction of rotation following peripheral administration of amphetamine were found to differ in their sensitization to amphetamine in two different behavioral paradigms. Rats which displayed leftward rotational biases developed greater sensitization and greater hormonal response to stress following sensitization. PMID:2841013

  2. [Effect of psychotropic substances on the development of alcoholic motivation in noninbred white rats].

    PubMed

    Burov, Iu V; Kampov-Polevoĭ, A V; Nikitina, L N

    1986-03-01

    The experiments have shown the capacity of antidepressant amitriptylin (0.5 mg/kg, i. p.) and tranquilizer phenazepam (0.1 mg/kg i. p.) to normalize the adaptive behaviour and almost completely prevent the development of alcohol motivation in animals with insufficient adaptive behaviour. It was established that in animals initially rejecting alcohol, chronic treatment with these drugs as well as d-amphetamine promoted alcohol motivation. The results obtained have proved our earlier hypothesis that preclinical search for drugs for the prevention and treatment of early stages of alcoholism is possible only in animals pre-selected according to their inclination to experimental alcoholism.

  3. Alcohol Alert

    MedlinePlus

    ... Us You are here Home » Alcohol Alert Alcohol Alert The NIAAA Alcohol Alert is a quarterly bulletin that disseminates important research ... text. To order single copies of select Alcohol Alerts, see ordering Information . To view publications in PDF ...

  4. Alcoholism - resources

    MedlinePlus

    Resources - alcoholism ... The following organizations are good resources for information on alcoholism : Alcoholics Anonymous -- www.aa.org Al-Anon/Alateen -- www.al-anon.org/home National Institute on Alcohol ...

  5. Alcoholic neuropathy

    MedlinePlus

    Neuropathy - alcoholic; Alcoholic polyneuropathy ... The exact cause of alcoholic neuropathy is unknown. It likely includes both a direct poisoning of the nerve by the alcohol and the effect of poor nutrition ...

  6. Alcohol Facts

    MedlinePlus

    ... raquo Alcohol Facts Alcohol Facts Listen Drinks like beer, malt liquor, wine, and hard liquor contain alcohol. Alcohol is the ingredient that gets you drunk. Hard liquor—such as whiskey, rum, or gin—has more ...

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

    SciTech Connect

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

    1987-08-01

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

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

    SciTech Connect

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

    1987-01-01

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

  9. Alcohol Alert: Genetics of Alcoholism

    MedlinePlus

    ... and Reports » Alcohol Alert » Alcohol Alert Number 84 Alcohol Alert Number 84 Print Version The Genetics of ... immune defense system. Genes Encoding Enzymes Involved in Alcohol Breakdown Some of the first genes linked to ...

  10. African American female basketball players: an examination of alcohol and drug behaviors.

    PubMed

    Bower, B L; Martin, M

    1999-11-01

    The use of drugs and alcohol by National Collegiate Athletic Association Division I African American female basketball players and their reasons for using these substances were examined. The investigation is part of a broader study investigating the use of alcohol, weight-loss products, tobacco, amphetamines, and anabolic steroids by female college athletes. Of the 50 athletes in this study, 72% reported having consumed alcoholic beverages, and 46% had engaged in binge drinking. Only 8% reported using either weight-loss or tobacco products, and there were no reports of using amphetamines or anabolic steroids. Usage patterns indicated that the athletes in the study were aware of the short-term negative effects of alcohol and tobacco; those respondents who did use these products greatly reduced their consumption during the competitive season. Factors found to influence use include social and peer influences and coaches' rules.

  11. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine inhalers regarded as prescription drugs. (a) Recurring reports of abuse and misuse of methamphetamine...

  12. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine inhalers regarded as prescription drugs. (a) Recurring reports of abuse and misuse of methamphetamine...

  13. Impairment related to blood amphetamine and/or methamphetamine concentrations in suspected drugged drivers.

    PubMed

    Gustavsen, Ingebjørg; Mørland, Jørg; Bramness, Jørgen G

    2006-05-01

    Experimental studies have investigated effects of low oral doses of amphetamine and methamphetamine on psychomotor functions, while less work has been done on effects of high doses taken by abusers in real-life settings. There are indications that intake of high doses may impair traffic related skills, and that abuse of amphetamines may cause hypersomnolence at the end-of-binge. The present study aimed at investigating the concentration-effect relationship between blood amphetamines concentrations and impairment in a population of real-life users. Eight hundred and seventy-eight cases with amphetamine or methamphetamine as the only drugs present in the blood samples were selected from the impaired driver registry at The Norwegian Institute of Public Health. In each case the police physician had concluded on whether the driver was impaired or not. 27% of the drivers were judged as not impaired, while 73% were judged as impaired. There was a positive relationship between blood amphetamines concentrations and impairment. The relationship reached a ceiling at blood amphetamines concentrations of 0.27-0.53 mg/l. Younger drivers were more often judged impaired than older drivers at similar concentrations. Despite the performance enhancing qualities of amphetamines demonstrated in some low dose laboratory experiments; this study revealed a positive relationship between blood amphetamines concentration and traffic related impairment.

  14. Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain.

    PubMed

    Freyberg, Zachary; Sonders, Mark S; Aguilar, Jenny I; Hiranita, Takato; Karam, Caline S; Flores, Jorge; Pizzo, Andrea B; Zhang, Yuchao; Farino, Zachary J; Chen, Audrey; Martin, Ciara A; Kopajtic, Theresa A; Fei, Hao; Hu, Gang; Lin, Yi-Ying; Mosharov, Eugene V; McCabe, Brian D; Freyberg, Robin; Wimalasena, Kandatege; Hsin, Ling-Wei; Sames, Dalibor; Krantz, David E; Katz, Jonathan L; Sulzer, David; Javitch, Jonathan A

    2016-02-16

    Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT's role in mediating amphetamine action in dopamine neurons, we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. In an ex vivo whole-brain preparation, fluorescent reporters of vesicular cargo and of vesicular pH reveal that amphetamine redistributes vesicle contents and diminishes the vesicle pH-gradient responsible for dopamine uptake and retention. This amphetamine-induced deacidification requires VMAT function and results from net H(+) antiport by VMAT out of the vesicle lumen coupled to inward amphetamine transport. Amphetamine-induced vesicle deacidification also requires functional dopamine transporter (DAT) at the plasma membrane. Thus, we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects.

  15. Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain

    PubMed Central

    Freyberg, Zachary; Sonders, Mark S.; Aguilar, Jenny I.; Hiranita, Takato; Karam, Caline S.; Flores, Jorge; Pizzo, Andrea B.; Zhang, Yuchao; Farino, Zachary J.; Chen, Audrey; Martin, Ciara A.; Kopajtic, Theresa A.; Fei, Hao; Hu, Gang; Lin, Yi-Ying; Mosharov, Eugene V.; McCabe, Brian D.; Freyberg, Robin; Wimalasena, Kandatege; Hsin, Ling-Wei; Sames, Dalibor; Krantz, David E.; Katz, Jonathan L.; Sulzer, David; Javitch, Jonathan A.

    2016-01-01

    Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT's role in mediating amphetamine action in dopamine neurons, we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. In an ex vivo whole-brain preparation, fluorescent reporters of vesicular cargo and of vesicular pH reveal that amphetamine redistributes vesicle contents and diminishes the vesicle pH-gradient responsible for dopamine uptake and retention. This amphetamine-induced deacidification requires VMAT function and results from net H+ antiport by VMAT out of the vesicle lumen coupled to inward amphetamine transport. Amphetamine-induced vesicle deacidification also requires functional dopamine transporter (DAT) at the plasma membrane. Thus, we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects. PMID:26879809

  16. Treatment of Attention Deficit/Hyperactivity Disorder with Amphetamine: Short-Term Effects on Family Interaction

    ERIC Educational Resources Information Center

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

    2008-01-01

    Objective: This research seeks to study the impact on family function after 3 months of treatment with amphetamine. Method: A total of 43 children, 6 to 11 years of age, with ADHD were treated with amphetamine for 3 months. Family function was studied before and after treatment by parent self-rating and independent observer ratings of videotaped…

  17. Functional neuroimaging of amphetamine-induced striatal neurotoxicity in the pleiotrophin knockout mouse model.

    PubMed

    Soto-Montenegro, María Luisa; Vicente-Rodríguez, Marta; Pérez-García, Carmen; Gramage, Esther; Desco, Manuel; Herradón, Gonzalo

    2015-03-30

    Amphetamine-induced neurotoxic effects have traditionally been studied using immunohistochemistry and other post-mortem techniques, which have proven invaluable for the definition of amphetamine-induced dopaminergic damage in the nigrostriatal pathway. However, these approaches are limited in that they require large numbers of animals and do not provide the temporal data that can be collected in longitudinal studies using functional neuroimaging techniques. Unfortunately, functional imaging studies in rodent models of drug-induced neurotoxicity are lacking. The aim of this study was to evaluate in vivo the changes in brain glucose metabolism caused by amphetamine in the pleiotrophin knockout mouse (PTN-/-), a genetic model with increased vulnerability to amphetamine-induced neurotoxic effects. We showed that administration of amphetamine causes a significantly greater loss of striatal tyrosine hydroxylase content in PTN-/- mice than in wild-type (WT) mice. In addition, [(18)F]-FDG-PET shows that amphetamine produces a significant decrease in glucose metabolism in the striatum and prefrontal cortex in the PTN-/- mice, compared to WT mice. These findings suggest that [(18)F]-FDG uptake measured by PET is useful for detecting amphetamine-induced changes in glucose metabolism in vivo in specific brain areas, including the striatum, a key feature of amphetamine-induced neurotoxicity.

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  19. Both positive reinforcement and conditioned aversion from amphetamine and from apomorphine in rats.

    PubMed

    Wise, R A; Yokel, R A; DeWit, H

    1976-03-26

    Rats learned to press a lever for intravenous injections of amphetamine or apomorphine. They also learned to avoid the taste of saccharin which was associated with experimenter-administered amphetamine or with self-administered apomorphine. Thus these, and presumably other, self-administered drugs serve as compound pharmacological stimuli, having both positively reinforcing and aversive properties.

  20. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine inhalers regarded as prescription drugs. (a) Recurring reports of abuse and misuse of methamphetamine...

  1. Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain.

    PubMed

    Freyberg, Zachary; Sonders, Mark S; Aguilar, Jenny I; Hiranita, Takato; Karam, Caline S; Flores, Jorge; Pizzo, Andrea B; Zhang, Yuchao; Farino, Zachary J; Chen, Audrey; Martin, Ciara A; Kopajtic, Theresa A; Fei, Hao; Hu, Gang; Lin, Yi-Ying; Mosharov, Eugene V; McCabe, Brian D; Freyberg, Robin; Wimalasena, Kandatege; Hsin, Ling-Wei; Sames, Dalibor; Krantz, David E; Katz, Jonathan L; Sulzer, David; Javitch, Jonathan A

    2016-01-01

    Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT's role in mediating amphetamine action in dopamine neurons, we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. In an ex vivo whole-brain preparation, fluorescent reporters of vesicular cargo and of vesicular pH reveal that amphetamine redistributes vesicle contents and diminishes the vesicle pH-gradient responsible for dopamine uptake and retention. This amphetamine-induced deacidification requires VMAT function and results from net H(+) antiport by VMAT out of the vesicle lumen coupled to inward amphetamine transport. Amphetamine-induced vesicle deacidification also requires functional dopamine transporter (DAT) at the plasma membrane. Thus, we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects. PMID:26879809

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

    ERIC Educational Resources Information Center

    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…

  3. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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...

  4. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 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...

  5. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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...

  6. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Code of Federal Regulations, 2010 CFR

    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...

  7. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 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...

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

    PubMed

    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

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

    PubMed

    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.

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

    PubMed Central

    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

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

    PubMed

    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. PMID:27208490

  12. Repeated corticosterone administration sensitizes the locomotor response to amphetamine.

    PubMed

    Deroche, V; Piazza, P V; Maccari, S; Le Moal, M; Simon, H

    1992-07-01

    Repeated exposures to stressful situations has been shown to increase individual reactivity to psychostimulants, although the biological factors involved in such stress-induced changes are still poorly understood. In this study, we investigated the role of corticosterone in the effects of stress on the response to psychostimulants. We found that repeated corticosterone administration (both 1.5 mg/kg, intraperitoneally and 50 micrograms/ml in drinking water, once per day for 15 days) increased the locomotor response to amphetamine (1.15 mg/kg, i.p.). At the doses used in these experiments, corticosterone administration induced similar increases in plasma levels of the hormone to those induced by stress. These results suggest that corticosterone secretion may be one of the mechanisms by which repeated stress increases the behavioral responses to amphetamine. Since an enhanced reactivity to psychostimulants has been found to be an index of a propensity for drug self-administration and a model of certain psychopathological conditions, these findings point to a role for glucocorticoids in such abnormal states. PMID:1515947

  13. Induction of a cytochrome P-450-dependent fatty acid monooxygenase in Bacillus megaterium by a barbiturate analog, 1-[2-phenylbutyryl]-3-methylurea.

    PubMed

    Wen, L P; Fulco, A J

    1985-05-01

    In previous publications from our laboratory, we reported that a soluble, cytochrome P-450-dependent fatty acid monooxygenase from Bacillus megaterium ATCC 14581 can be induced by phenobarbital and a variety of other barbiturates. The tested barbiturates showed an excellent correlation between increasing lipophilicity and increasing inducer potency (Kim BH, Fulco AJ; Biochem Biophys Res Commun 116: 843-850, 1983). The only exception proved to be mephobarbital (N-methylphenobarbital) which, although more lipophilic than phenobarbital, is not an inducer of fatty acid monooxygenase activity. We have now found that 1-[2-phenylbutyryl]-3-methylurea (PBMU), an acylurea that can be derived from mephobarbital by hydrolytic cleavage of the barbiturate ring, is an excellent inducer of this activity. Paradoxically, the addition of mephobarbital to the bacterial growth medium containing PBMU significantly enhances the apparent potency of the acylurea to induce fatty acid monooxygenase activity as measured in cell-free extracts. When cell-free extracts of cells grown separately in PBMU or mephobarbital are mixed no enhancement of activity is seen. This finding suggests that the effect of mephobarbital is to somehow increase the efficiency of PBMU as an inducer of the P-450-dependent fatty acid monooxygenase rather than to induce an activator of this enzyme or a rate-limiting component of the monooxygenase system. Finally, both mephobarbital and PBMU induce the synthesis of total cytochrome P-450 in B. megaterium although PBMU is a much more potent P-450 inducer. For cytochrome P-450 induction, however, there is no synergistic or even additive effect when mephobarbital and PBMU are used together in the bacterial growth medium. PMID:3927150

  14. Intermediates of Krebs cycle correct the depression of the whole body oxygen consumption and lethal cooling in barbiturate poisoning in rat.

    PubMed

    Ivnitsky, Jury Ju; Schäfer, Timur V; Malakhovsky, Vladimir N; Rejniuk, Vladimir L

    2004-10-01

    Rats poisoned with one LD50 of thiopental or amytal are shown to increase oxygen consumption when intraperitoneally given sucinate, malate, citrate, alpha-ketoglutarate, dimethylsuccinate or glutamate (the Krebs cycle intermediates or their precursors) but not when given glucose, pyruvate, acetate, benzoate or nicotinate (energy substrates of other metabolic stages etc). Survival was increased with succinate or malate from control groups, which ranged from 30-83% to 87-100%. These effects were unrelated to respiratory depression or hypoxia as judged by little or no effect of succinate on ventilation indices and by the lack of effect of oxygen administration. Body cooling of comatose rats at ambient temperature approximately 19 degrees C became slower with succinate, the rate of cooling correlated well with oxygen consumption decrease. Succinate had no potency to modify oxygen consumption and body temperature in intact rats. A condition for antidote effect of the Krebs intermediate was sufficiently high dosage (5 mmol/kg), further dose increase made no odds. Repeated dosing of succinate had more marked protective effect, than a single one, to oxygen consumption and tended to promote the attenuation of lethal effect of barbiturates. These data suggest that suppression of whole body oxygen consumption with barbiturate overdose could be an important contributor to both body cooling and mortality. Intermediates of Krebs cycle, not only succinate, may have a pronounced therapeutic effect under the proper treatment regimen. Availability of Krebs cycle intermediates may be a limiting factor for the whole body oxygen consumption in barbiturate coma, its role in brain needs further elucidation.

  15. Reinforcing Effects of d-Amphetamine: Influence of Novel Ratios on a Progressive-Ratio Schedule

    PubMed Central

    Sevak, Rajkumar J.; Stoops, William W.; Glaser, Paul E.A.; Hays, Lon R.; Rush, Craig R.

    2013-01-01

    Progressive-ratio schedules are useful for studying reinforcing effects of drugs. Previous human laboratory studies showed that d-amphetamine significantly increased break points relative to placebo levels. However, the magnitude of the increase was modest, which may be attributable to rather high levels of placebo responding. We utilized novel response requirements under the modified progressive-ratio schedule and hypothesized that the altered range of response requirements would decrease responding for placebo and increase responding for d-amphetamine. Eight participants completed the study. The participants first sampled oral doses of d-amphetamine (0, 8, 16 and 24 mg). In subsequent sessions, participants were offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure with response requirements ranging from 400 to 1800 mouse clicks. A battery of participant-rated drug-effect questionnaires, a performance measure and cardiovascular measures were included in orderto characterize more fully the effects of d-amphetamine. Placebo maintained low levels of responding. The intermediate dose of d-amphetamine increased responding significantly above placebo levels. d-Amphetamine produced prototypical subject-rated effects that were an orderly function of dose. The present data suggest that the modified response requirements resulted in lower levels of placebo taking and a larger separation between number of placebo and d-amphetamine capsules earned. PMID:20944503

  16. Comparative symptomatological and evoked potential studies with d-amphetamine, thioridazine, and placebo in hyperkinetic children.

    PubMed

    Saletu, B; Saletu, M; Simeon, J; Viamontes, G; Itil, T M

    1975-06-01

    In a double-blind study, 62 hyperkinetic children were randomly assigned to 8 weeks of treatment with either placebo, thioridazine, or d-amphetamine. The overall clinical symptomatology improved with all three substances, although d-amphetamine was significantly superior to placebo and thioridazine. Out of eight symptom clusters rated by the parents, two improved significantly with placebo, one with thioridazine, and six with d-amphetamine. The d-amphetamine was superior to placebo in reducing muscular tension and superior to thioridazine in decreasing hyperactive-impulsive behavior, psychosomatic problems, and muscular tension. Out of four teachers' symptom clusters, inattentive-passive behavior was significantly improved by thioridazine (which was also superior to placebo), while hyperactivity was reduced by d-amphetamine. Quantitative evaluation of visual evoked potentials (VEPs) revealed an increase in latencies and decrease in amplitudes during thioridazine treatment. Paradoxically, d-amphetamine also increased latencies, while tending to augment amplitudes. Regression and correlation analysis of clinical symptomatology with VEP variables showed that the shorter the pretreatment latencies and the higher the amplitudes, the more disturbed was the child. Short latencies and small amplitudes in the pretreatment period were predictors of good therapeutic outcome with subsequent thioridazine treatment, while short latencies and high amplitudes were indicative of such with d-amphetamine treatment. During therapy, the greater the drug-induced augmentation of latencies, the greater the clinical improvement. Finally, VEP differences between therapy-responsive and -resistant patients were explored and discussed.

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

    PubMed

    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.

  18. AMPHETAMINE AUGMENTS VESICULAR DOPAMINE RELEASE IN THE DORSAL AND VENTRAL STRIATUM THROUGH DIFFERENT MECHANISMS

    PubMed Central

    Avelar, Alicia J.; Juliano, Steven A.; Garris, Paul A.

    2013-01-01

    Amphetamine has well-established actions on presynaptic dopamine signaling, such as inhibiting uptake and degradation, activating synthesis, depleting vesicular stores, and promoting dopamine-transporter reversal and non-exocytotic release. Recent in vivo studies have identified an additional mechanism: augmenting vesicular release. Here we investigated how amphetamine elicits this effect. Our hypothesis was that amphetamine enhances vesicular dopamine release in dorsal and ventral striata by differentially targeting dopamine synthesis and degradation. In urethane-anesthetized rats, we employed voltammetry to monitor dopamine, electrical stimulation to deplete stores or assess vesicular release and uptake, and pharmacology to isolate degradation and synthesis. While amphetamine increased electrically evoked dopamine levels, inhibited uptake, and up-regulated vesicular release in both striatal sub-regions in controls, this psychostimulant elicited region-specific effects on evoked levels and vesicular release but not uptake in drug treatments. Evoked levels better correlated with vesicular release compared to uptake, supporting enhanced vesicular release as an important amphetamine mechanism. Taken together, these results suggested that amphetamine enhances vesicular release in the dorsal striatum by activating dopamine synthesis and inhibiting dopamine degradation, but targeting an alternative mechanism in the ventral striatum. Region-distinct activation of vesicular dopamine release highlights complex cellular actions of amphetamine and may have implications for its behavioral effects. PMID:23406303

  19. Amphetamine augments vesicular dopamine release in the dorsal and ventral striatum through different mechanisms.

    PubMed

    Avelar, Alicia J; Juliano, Steven A; Garris, Paul A

    2013-05-01

    Amphetamine has well-established actions on pre-synaptic dopamine signaling, such as inhibiting uptake and degradation, activating synthesis, depleting vesicular stores, and promoting dopamine-transporter reversal and non-exocytotic release. Recent in vivo studies have identified an additional mechanism: augmenting vesicular release. In this study, we investigated how amphetamine elicits this effect. Our hypothesis was that amphetamine enhances vesicular dopamine release in dorsal and ventral striata by differentially targeting dopamine synthesis and degradation. In urethane-anesthetized rats, we employed voltammetry to monitor dopamine, electrical stimulation to deplete stores or assess vesicular release and uptake, and pharmacology to isolate degradation and synthesis. While amphetamine increased electrically evoked dopamine levels, inhibited uptake, and up-regulated vesicular release in both striatal sub-regions in controls, this psychostimulant elicited region-specific effects on evoked levels and vesicular release but not uptake in drug treatments. Evoked levels better correlated with vesicular release compared with uptake, supporting enhanced vesicular release as an important amphetamine mechanism. Taken together, these results suggested that amphetamine enhances vesicular release in the dorsal striatum by activating dopamine synthesis and inhibiting dopamine degradation, but targeting an alternative mechanism in the ventral striatum. Region-distinct activation of vesicular dopamine release highlights complex cellular actions of amphetamine and may have implications for its behavioral effects.

  20. METHAMPHETAMINE SELF-ADMINISTRATION IN HUMANS DURING D-AMPHETAMINE MAINTENANCE

    PubMed Central

    Pike, Erika; Stoops, William W.; Hays, Lon R.; Glaser, Paul E. A.; Rush, Craig R.

    2014-01-01

    Agonist replacement may be a viable treatment approach for managing stimulant use disorders. This study sought to determine the effects of d-amphetamine maintenance on methamphetamine self-administration in stimulant using human participants. We predicted d-amphetamine maintenance would reduce methamphetamine self-administration. Eight participants completed the protocol, which tested two d-amphetamine maintenance conditions in counter-balanced order (0 and 40 mg/day). Participants completed 4 experimental sessions under each maintenance condition in which they first sampled one of four doses of intranasal methamphetamine (0, 10, 20, or 30 mg). Participants then had the opportunity to respond on a computerized progressive ratio task to earn portions of the sampled methamphetamine dose. Subject-rated drug-effect and physiological measures were completed at regular intervals prior to and after sampling methamphetamine. Methamphetamine was self-administered as an orderly function of dose regardless of the maintenance condition. Methamphetamine produced prototypical subject-rated effects on 13 items of the drug-effects questionnaires, 10 of which were attenuated by d-amphetamine maintenance (e.g., increased ratings were attenuated on items such as Any Effect, Like Drug, and Willing to Take Again on the Drug Effect Questionnaire). Methamphetamine produced significant increases in systolic blood pressure, which were attenuated by d-amphetamine maintenance compared to placebo maintenance. Methamphetamine was well tolerated during d-amphetamine maintenance and no adverse events occurred. Although d-amphetamine attenuated some subject-rated effects of methamphetamine, the self-administration results are concordant with those of clinical trials showing that d-amphetamine did not reduce methamphetamine use. Unique pharmacological approaches may be needed for treating amphetamine use disorders. PMID:25154010

  1. Methamphetamine self-administration in humans during D-amphetamine maintenance.

    PubMed

    Pike, Erika; Stoops, William W; Hays, Lon R; Glaser, Paul E A; Rush, Craig R

    2014-12-01

    Agonist replacement may be a viable treatment approach for managing stimulant use disorders. This study sought to determine the effects of D-amphetamine maintenance on methamphetamine self-administration in stimulant using human participants. We predicted that D-amphetamine maintenance would reduce methamphetamine self-administration. Eight participants completed the protocol, which tested 2 D-amphetamine maintenance conditions in counterbalanced order (0 and 40 mg/d). Participants completed 4 experimental sessions under each maintenance condition in which they first sampled 1 of 4 doses of intranasal methamphetamine (0, 10, 20, or 30 mg). Participants then had the opportunity to respond on a computerized progressive-ratio task to earn portions of the sampled methamphetamine dose. Subject-rated drug effect and physiological measures were completed at regular intervals prior to and after sampling methamphetamine. Methamphetamine was self-administered as an orderly function of dose regardless of the maintenance condition. Methamphetamine produced prototypical subject-rated effects on 12 items of the drug-effects questionnaires, 8 of which were attenuated by D-amphetamine maintenance (eg, increased ratings were attenuated on items such as Any Effect, Like Drug, and Willing to Take Again on the Drug Effect Questionnaire). Methamphetamine produced significant increases in systolic blood pressure, which were attenuated by D-amphetamine maintenance compared to placebo maintenance. Methamphetamine was well tolerated during D-amphetamine maintenance and no adverse events occurred. Although D-amphetamine attenuated some subject-rated effects of methamphetamine, the self-administration results are concordant with those of clinical trials showing that D-amphetamine did not reduce methamphetamine use. Unique pharmacological approaches may be needed for treating amphetamine use disorders.

  2. Effects of diphenyl diselenide on behavioral and biochemical changes induced by amphetamine in mice.

    PubMed

    Figueira, Fernanda Hernandes; Leal, Caroline Queiroz; Reis, Elizete de Moraes; Röpke, Jivago; Wagner, Caroline; da Rocha, João Batista Teixeira; Fachinetto, Roselei

    2015-02-01

    Diphenyl diselenide (PhSe)2, an organoselenium compound, has been studied as a potential pharmacological agent in different in vitro and in vivo models, mainly due to its antioxidant properties. However, there are few studies concerning the effects of (PhSe)2 on dopaminergic system. Thus, the purpose of the present study was to evaluate the effects of acute and sub-chronic treatment of (PhSe)2 on amphetamine-induced behavioral and biochemical parameters. In acute protocol, mice were pre-treated with 5 or 10 mg/kg of (PhSe)2 and 30 min after, amphetamine was administered. In sub-chronic protocol, mice were pre-treated with 5 or 10 mg/kg of (PhSe)2 during 7 days and 24 h after, amphetamine was administered. Twenty-five minutes after amphetamine administration, behavioral (crossing, rearing, time of stereotypy and immobility) and biochemical (MAO activity, DCFH-DA oxidation, protein and non-protein thiol groups) parameters were analyzed. Amphetamine increased the number of crossing and rearing and (PhSe)2 prevented only the increase in the number of crossings when acutely administered to mice. Furthermore, amphetamine increased stereotypy and time of immobility in mice. (PhSe)2, at 10 mg/kg, increased per se the stereotypy and time of immobility when sub-chronically administered. (PhSe)2, at 10 mg/kg, potentiated the stereotypy caused by amphetamine in both protocols. Sub-chronic treatment with (PhSe)2 either alone (5 and 10 mg/kg) or in combination (10 mg/kg) with amphetamine decreased brain MAO-B activity. Oxidative stress parameters were not modified by (PhSe)2 and/or amphetamine treatments. In conclusion, sub-chronic administration of (PhSe)2 can promote a behavioral sensitization that seems to be, at least in part, dependent of MAO-B inhibition.

  3. REGULATION OF NETRIN-1 RECEPTORS BY AMPHETAMINE IN THE ADULT BRAIN

    PubMed Central

    YETNIKOFF, L.; LABELLE-DUMAIS, C.; FLORES, C.

    2016-01-01

    Netrin-1 is a guidance cue molecule fundamental to the organization of neuronal connectivity during development. Netrin-1 and its receptors, deleted in colorectal cancer (DCC) and UNC-5 homologues (UNC-5), continue to be expressed in the adult brain, although neither their function nor the kinds of events that activate their expression are known. Two lines of evidence suggest a role for netrin-1 in amphetamine-induced dopamine plasticity in the adult. First, DCC is highly expressed by adult dopamine neurons. Second, adult mice with reduced DCC levels do not develop amphetamine-induced behavioral sensitization. To explore the role of netrin-1 in amphetamine-induced plasticity, we examined the effects of sensitizing treatment regimens of amphetamine on DCC and/or UNC-5 protein expression in the adult rat. These treatments produced striking and enduring increases in DCC and UNC-5 expression in the cell body, but not terminal regions, of the mesocorticolimbic dopamine system. Notably, neuroadaptations in the cell body region of mesocorticolimbic dopamine neurons underlie the development of sensitization to the effects of amphetamine. Furthermore, these localized amphetamine-induced changes were prevented by co-treatment with an N-methyl-D-aspartate receptor antagonist, a treatment known to block the development of amphetamine-induced sensitization of behavioral activation, dopamine release and motivated behavior. Using immunohistochemistry, we showed that both DCC and UNC-5 receptors are highly expressed by adult mesocorticolimbic dopamine neurons. These results provide the first evidence that repeated exposure to a stimulant drug such as amphetamine affects netrin-1 receptor expression in the adult brain. Taken together, our findings suggest that changes in netrin-1 receptor expression may play a role in the lasting effects of exposure to amphetamine and other stimulant drugs. PMID:17996376

  4. Myths about drinking alcohol

    MedlinePlus

    ... to. I spend a lot of time getting alcohol, drinking alcohol, or recovering from the effects of alcohol. ... Institute on Alcohol Abuse and Alcoholism. Overview of Alcohol Consumption. www.niaaa.nih.gov/alcohol-health/overview-alcohol- ...

  5. Chronic social stress conditions differentially modify vulnerability to amphetamine self-administration.

    PubMed

    Lemaire, V; Deminière, J M; Mormède, P

    1994-06-27

    Using social instability and cohabitation with females as chronic stress, we observed that neuroendocrine systems were differentially activated according to the experimental design. We show here that amphetamine self-administration, a paradigm to study the reinforcing effects of psychostimulants, is also differentially affected by these conditions. Coexistence with females increases amphetamine self-administration and this effect is reduced when social instability is superimposed. On the other hand, locomotor response to amphetamine is not modified by either social factor, suggesting a specific involvement of a subset of dopaminergic neurons. PMID:7953651

  6. Experimental Investigation on Terahertz Spectra of Amphetamine Type Stimulants

    NASA Astrophysics Data System (ADS)

    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.

  7. Unpredictable saccharin reinforcement enhances locomotor responding to amphetamine.

    PubMed

    Singer, B F; Scott-Railton, J; Vezina, P

    2012-01-01

    Drug-naïve, non-deprived rats were trained to lever press for saccharin under fixed-ratio (FR) or variable-ratio (VR) schedules of reinforcement. Rats trained on the VR schedule in which saccharin reinforcement was not predicted by a fixed number of lever presses subsequently showed an enhanced locomotor response to a threshold amphetamine challenge injection (0.5mg/kg IP) administered 2 weeks following the last saccharin session. This finding suggests that chronic exposure to gambling-like conditions of uncertain reinforcement can induce neuroadaptations in brain reward systems that are similar to those produced by repeated psychostimulant exposure and may lead to the development of addictive behaviors.

  8. Exendin-4 Decreases Amphetamine-induced Locomotor Activity

    PubMed Central

    Erreger, Kevin; Davis, Adeola R.; Poe, Amanda M.; Greig, Nigel H.; Stanwood, Gregg D.; Galli, Aurelio

    2012-01-01

    Glucagon-like peptide-1 (GLP-1) is released in response to nutrient ingestion and is a regulator of energy metabolism and consummatory behaviors through both peripheral and central mechanisms. The GLP-1 receptor (GLP-1R) is widely distributed in the central nervous system, however little is known about how GLP-1Rs regulate ambulatory behavior. The abused psychostimulant amphetamine (AMPH) promotes behavioral locomotor activity primarily by inducing the release of the neurotransmitter dopamine. Here, we identify the GLP-1R agonist exendin-4 (Ex-4) as a modulator of behavioral activation by AMPH. We report that in rats a single acute administration of Ex-4 decreases both basal locomotor activity as well as AMPH-induced locomotor activity. Ex-4 did not induce behavioral responses reflecting anxiety or aversion. Our findings implicate GLP-1R signaling as a novel modulator of psychostimulant-induced behavior and therefore a potential therapeutic target for psychostimulant abuse. PMID:22465309

  9. PI3K signaling supports amphetamine-induced dopamine efflux.

    PubMed

    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.

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

    PubMed

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

    2016-09-01

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

  11. 3D-QSAR Studies on Barbituric Acid Derivatives as Urease Inhibitors and the Effect of Charges on the Quality of a Model

    PubMed Central

    Ul-Haq, Zaheer; Ashraf, Sajda; Al-Majid, Abdullah Mohammed; Barakat, Assem

    2016-01-01

    Urease enzyme (EC 3.5.1.5) has been determined as a virulence factor in pathogenic microorganisms that are accountable for the development of different diseases in humans and animals. In continuance of our earlier study on the helicobacter pylori urease inhibition by barbituric acid derivatives, 3D-QSAR (three dimensional quantitative structural activity relationship) advance studies were performed by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods. Different partial charges were calculated to examine their consequences on the predictive ability of the developed models. The finest developed model for CoMFA and CoMSIA were achieved by using MMFF94 charges. The developed CoMFA model gives significant results with cross-validation (q2) value of 0.597 and correlation coefficients (r2) of 0.897. Moreover, five different fields i.e., steric, electrostatic, and hydrophobic, H-bond acceptor and H-bond donors were used to produce a CoMSIA model, with q2 and r2 of 0.602 and 0.98, respectively. The generated models were further validated by using an external test set. Both models display good predictive power with r2pred ≥ 0.8. The analysis of obtained CoMFA and CoMSIA contour maps provided detailed insight for the promising modification of the barbituric acid derivatives with an enhanced biological activity. PMID:27144563

  12. 3D-QSAR Studies on Barbituric Acid Derivatives as Urease Inhibitors and the Effect of Charges on the Quality of a Model.

    PubMed

    Ul-Haq, Zaheer; Ashraf, Sajda; Al-Majid, Abdullah Mohammed; Barakat, Assem

    2016-01-01

    Urease enzyme (EC 3.5.1.5) has been determined as a virulence factor in pathogenic microorganisms that are accountable for the development of different diseases in humans and animals. In continuance of our earlier study on the helicobacter pylori urease inhibition by barbituric acid derivatives, 3D-QSAR (three dimensional quantitative structural activity relationship) advance studies were performed by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods. Different partial charges were calculated to examine their consequences on the predictive ability of the developed models. The finest developed model for CoMFA and CoMSIA were achieved by using MMFF94 charges. The developed CoMFA model gives significant results with cross-validation (q²) value of 0.597 and correlation coefficients (r²) of 0.897. Moreover, five different fields i.e., steric, electrostatic, and hydrophobic, H-bond acceptor and H-bond donors were used to produce a CoMSIA model, with q² and r² of 0.602 and 0.98, respectively. The generated models were further validated by using an external test set. Both models display good predictive power with r²pred ≥ 0.8. The analysis of obtained CoMFA and CoMSIA contour maps provided detailed insight for the promising modification of the barbituric acid derivatives with an enhanced biological activity. PMID:27144563

  13. Daily Isoflurane Exposure Increases Barbiturate Insensitivity in Medullary Respiratory and Cortical Neurons via Expression of ε-Subunit Containing GABA ARs

    PubMed Central

    Hengen, Keith B.; Nelson, Nathan R.; Stang, Kyle M.; Johnson, Stephen M.; Smith, Stephanie M.; Watters, Jyoti J.; Mitchell, Gordon S.; Behan, Mary

    2015-01-01

    The parameters governing GABAA receptor subtype expression patterns are not well understood, although significant shifts in subunit expression may support key physiological events. For example, the respiratory control network in pregnant rats becomes relatively insensitive to barbiturates due to increased expression of ε-subunit-containing GABAARs in the ventral respiratory column. We hypothesized that this plasticity may be a compensatory response to a chronic increase in inhibitory tone caused by increased central neurosteroid levels. Thus, we tested whether increased inhibitory tone was sufficient to induce ε-subunit upregulation on respiratory and cortical neurons in adult rats. Chronic intermittent increases in inhibitory tone in male and female rats was induced via daily 5-min exposures to 3% isoflurane. After 7d of treatment, phrenic burst frequency was less sensitive to barbiturate in isoflurane-treated male and female rats in vivo. Neurons in the ventral respiratory group and cortex were less sensitive to pentobarbital in vitro following 7d and 30d of intermittent isoflurane-exposure in both male and female rats. The pentobarbital insensitivity in 7d isoflurane-treated rats was reversible after another 7d. We hypothesize that increased inhibitory tone in the respiratory control network and cortex causes a compensatory increase in ε-subunit-containing GABAARs. PMID:25748028

  14. The shapes of neurotransmitters by millimetrewave spectroscopy: amphetamine

    NASA Astrophysics Data System (ADS)

    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. Ethanol enhancement of cocaine- and amphetamine-regulated transcript mRNA and peptide expression in the nucleus accumbens.

    PubMed

    Salinas, Armando; Wilde, Jennifer D; Maldve, Regina E

    2006-04-01

    Cocaine- and amphetamine-regulated transcript (CART) is a peptide neurotransmitter that has been implicated in drug reward and reinforcement. CART mRNA and peptide expression are highly concentrated in several compartments of the mesolimbic reward pathway. Several lines of evidence suggest that CART peptides may contribute to rewarding behaviors and the addiction liability of psychostimulants; however, there are no reports of basic work concerning CART in relation to alcohol and mechanisms of alcohol dependence development. Therefore, in this study we investigated the response of CART transcript and peptide to acute ethanol administration in vivo. Rats were administered ethanol (1 g/kg or 3.5 g/kg, 1 h, ip) and CART expression was measured by RT-PCR in the nucleus accumbens (NAcc). Ethanol (3.5 g/kg) increased CART transcription markedly. The interactions of dopamine on ethanol-induced CART expression were further evaluated pharmacologically using D1 and D2/D3 receptor antagonists. Both SCH 23390 (0.25 mg/kg) or raclopride (0.2 mg/kg) pre-treatment significantly suppressed ethanol-enhancement of CART mRNA transcription. Confocal immunofluorescence microscopy revealed that CART peptide immunoreactivity was also enhanced in both the core and the shell of the NAcc by ethanol administration. These findings demonstrate that CART mRNA and peptide expression are responsive to acute ethanol administrated in vivo and suggests that CART peptides may be important in regulating the rewarding and reinforcing properties of ethanol. PMID:16539670

  16. Alcohol and Alcoholism.

    ERIC Educational Resources Information Center

    National Inst. of Mental Health (DHEW), Chevy Chase, MD. National Clearinghouse for Mental Health Information.

    This concise survey presents some of the highlights of modern research on drinking and alcoholism, as based on technical articles published in the scientific literature and the views expressed by leading authorities in the field. Contents include discussions about: (1) the nature and scope of the problem; (2) the chemical composition of alcoholic…

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

    PubMed Central

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

    2012-01-01

    Maturation of mesocorticolimbic dopamine systems occurs during adolescence, and exposure to social stress during this period results in behavioral dysfunction including substance abuse disorders. Adult male rats exposed to repeated social defeat in adolescence exhibit reduced basal dopamine tissue content in the medial prefrontal cortex, altered dopamine tissue content in corticoaccumbal dopamine regions following acute amphetamine, and increased amphetamine conditioned place preference following repeated amphetamine treatment. Such changes may reflect altered amphetamine-induced extracellular dopamine release in the corticoaccumbal regions. Therefore, we used in vivo microdialysis to measure extracellular dopamine simultaneously within the medial prefrontal cortex and nucleus accumbens core of previously defeated rats and controls, in response to either acute or repeated (7 daily injections) of amphetamine (1.0 mg/kg). Locomotion responses to acute / repeated amphetamine were also assessed the day prior to taking dopamine measurements. Adolescent defeat potentiated adult locomotion responses to acute amphetamine, which was negatively correlated with attenuated amphetamine-induced dopamine release in the medial prefrontal cortex, but there was no difference in amphetamine-induced accumbal dopamine release. However, both locomotion and corticoaccumbal dopamine responses to repeated amphetamine were equivalent between previously defeated rats and controls. These data suggest adolescent defeat enhances behavioral responses to initial amphetamine exposure as a function of diminished prefrontal cortex dopamine activity, which may be sufficient to promote subsequently enhanced seeking of drug-associated cues. Interestingly, repeated amphetamine treatment appears to normalize amphetamine-elicited locomotion and cortical dopamine responses observed in adult rats exposed to adolescent social defeat, providing implications for treating stress-induced dopamine dysfunction

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

    PubMed

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

    2016-02-01

    Methamphetamine is a globally abused drug that is metabolized to amphetamine, which also produces abuse-related behavioral effects. However, the contributing role of methamphetamine metabolism to amphetamine in methamphetamine's abuse-related subjective effects is unknown. This preclinical study was designed to determine 1) the relationship between plasma methamphetamine levels and methamphetamine discriminative stimulus effects and 2) the contribution of the methamphetamine metabolite amphetamine in the discriminative stimulus effects of methamphetamine in rhesus monkeys. Adult male rhesus monkeys (n=3) were trained to discriminate 0.18mg/kg intramuscular (+)-methamphetamine from saline in a two-key food-reinforced discrimination procedure. Time course of saline, (+)-methamphetamine (0.032-0.32mg/kg), and (+)-amphetamine (0.032-0.32mg/kg) discriminative stimulus effects were determined. Parallel pharmacokinetic studies were conducted in the same monkeys to determine plasma methamphetamine and amphetamine levels after methamphetamine administration and amphetamine levels after amphetamine administration for correlation with behavior in the discrimination procedure. Both methamphetamine and amphetamine produced full, ≥90%, methamphetamine-like discriminative stimulus effects. Amphetamine displayed a slightly, but significantly, longer duration of action than methamphetamine in the discrimination procedure. Both methamphetamine and amphetamine behavioral effects were related to methamphetamine and amphetamine plasma levels by a clockwise hysteresis loop indicating acute tolerance had developed to the discriminative stimulus effects. Furthermore, amphetamine levels after methamphetamine administration were absent when methamphetamine stimulus effects were greatest and peaked when methamphetamine discriminative stimulus effects returned to saline-like levels. Overall, these results demonstrate the methamphetamine metabolite amphetamine does not contribute to

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

    ERIC Educational Resources Information Center

    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)

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

    PubMed

    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. Potential Adverse Effects of Amphetamine Treatment on Brain and Behavior: A Review

    PubMed Central

    Berman, Steven M.; Kuczenski, Ronald; McCracken, James T.; London, Edythe D.

    2009-01-01

    Rationale Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority 1. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Findings Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several-fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central

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

    PubMed

    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.

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

    PubMed

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

    2015-08-01

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

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  5. Contextual conditioning enhances the psychostimulant and incentive properties of d-amphetamine in humans

    PubMed Central

    Childs, Emma; de Wit, Harriet

    2014-01-01

    Learned associations between drugs and the places they are used are critical to the development of drug addiction. Contextual conditioning has long been studied in animals as an indirect measure of drug reward, but little is known about the process in humans. Here, we investigated de novo contextual conditioning with d-amphetamine in healthy humans (n = 34). Volunteers underwent four conditioning sessions conducted in two testing rooms with double-blind, alternating d-amphetamine (20 mg) and placebo administration. Before conditioning procedures began, they rated the two rooms to examine pre-existing preferences. One group (Paired, n = 19) always received d-amphetamine in their least preferred room and placebo in the other during conditioning sessions. Another group (Unpaired, n = 15) received d-amphetamine and placebo in both rooms. Subjective drug effects were monitored at repeated times. At a separate re-exposure test, preference ratings for the drug-associated room were increased among the Paired group only, and more subjects in the Paired than the Unpaired group switched their preference to their initially least preferred room. Also, ratings of d-amphetamine drug liking independently predicted room liking at test among the Paired group only. Further, Paired group subjects reported greater stimulation and drug craving after d-amphetamine on the second administration, relative to the first. This study supports preliminary findings that humans, like animals, develop a preference for a place associated with d-amphetamine that is related to its subjective effects. These findings also suggest that experiencing d-amphetamine in a consistent environment produces context-dependent changes in its subjective effects, including an enhanced rewarding efficacy and abuse potential. PMID:22129527

  6. Effects of amphetamine on the human brain opioid system--a positron emission tomography study.

    PubMed

    Guterstam, Joar; Jayaram-Lindström, Nitya; Cervenka, Simon; Frost, J James; Farde, Lars; Halldin, Christer; Franck, Johan

    2013-05-01

    Studies in rodents have shown that psychostimulant drugs such as cocaine and amphetamine cause endorphin release in the brain reward system. There is also evidence for the involvement of the opioid system in human psychostimulant dependence. The acute effects of an i.v. psychostimulant drug on the brain opioid system, however, have not yet been investigated in humans. We hypothesized that an i.v. dose of amphetamine as compared to placebo would cause an opioid release in the human brain reward system, measurable as a reduction of the binding potential of the μ-opioid receptor radioligand [(11)C]carfentanil. Ten healthy young men were examined using positron emission tomography (PET) and [(11)C]carfentanil in three sessions: at baseline; after placebo; after an i.v. amphetamine dose of 0.3 mg/kg bodyweight. The order of amphetamine and placebo was double-blinded and randomized. PET examinations were performed with a Siemens high resolution research tomograph. Data were analysed with the simplified reference tissue model, applying manually drawn regions of interest for every subject. Using repeated measures analysis of variance, we found no significant differences in [(11)C]carfentanil binding potential between amphetamine and placebo conditions in any of the investigated brain regions. In contrast to data from rodent studies and a recent study of oral amphetamine administration in humans, an i.v. dose of amphetamine does not cause any acute opioid release in healthy human subjects. The postulated role of the opioid system in mediating the effects of amphetamine needs to be further investigated in animal models of the disease as well as in patient populations.

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

    PubMed

    Wong, Jamie K; Steward, Oswald

    2012-02-01

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

  8. Midkine regulates amphetamine-induced astrocytosis in striatum but has no effects on amphetamine-induced striatal dopaminergic denervation and addictive effects: functional differences between pleiotrophin and midkine.

    PubMed

    Gramage, E; Martín, Y B; Ramanah, P; Pérez-García, C; Herradón, G

    2011-09-01

    Midkine (MK), a neurotrophic factor with important roles in survival and differentiation of dopaminergic neurons, is upregulated in different brain areas after administration of different drugs of abuse suggesting MK could modulate drugs of abuse-induced pharmacological or neuroadaptative effects. To test this hypothesis, we have studied the effects of amphetamine administration in MK genetically deficient (MK-/-) and wild-type (MK+/+) mice. In conditioning studies, we found that amphetamine induces conditioned place preference (CPP) similarly in both MK-/- and MK+/+ mice. In immunohistochemistry studies, we found that amphetamine (10 mg/kg, four times, every 2 h) causes a similar striatal dopaminergic denervation in both MK-/- and MK+/+ mice. However, we detected a significant increase of glial fibrillary acidic protein (GFAP)-positive cells in the striatum of amphetamine-treated MK-/- mice compared to MK+/+ mice, suggesting an enhanced amphetamine-induced astrocytosis in absence of endogenous MK. Interestingly, the levels of expression of the MK receptor, receptor protein tyrosine phosphatase (RPTP) β/ζ, in the striatum were not found to be changed by the drug administration or the mouse genotype. In a similar manner the phosphorylation levels of RPTP β/ζ substrates with important roles in survival of dopaminergic neurons, Fyn kinase and TrkA, and of the MAP kinases ERK1/2, were unaffected by the drug or the genotype. The data clearly suggest that endogenous MK limits amphetamine-induced astrocytosis through Fyn-, TrkA- and ERK1/2-independent mechanisms and identify previously unexpected functional differences between MK and pleiotrophin, the only other member of the MK family of growth factors, in the modulation of effects of drugs of abuse.

  9. The acute effects of d-amphetamine and d-methamphetamine on ERP components in humans.

    PubMed

    Silber, B; Croft, R; Camfield, D A; Downey, L A; Papafotiou, K; Stough, C

    2012-07-01

    While a number of behavioural studies have been conducted to investigate the acute effects of amphetamines on tasks of attention and information processing, there is currently a scarcity of research concerning their electrophysiological effects in healthy adults. It is also unclear as to whether amphetamines exert effects on stimulus evaluation or response selection. In two studies, independent groups of twenty healthy illicit stimulant users aged between 21 and 32 years were administered 0.42 mg/kg d-amphetamine versus placebo, and 0.42 mg/kg d-methamphetamine versus placebo respectively, and completed an auditory oddball task on two separate testing days. A 62-channel EEG was recorded during the completion of the task, and the effects of amphetamines on N200 and P300 ERP components were analysed. d-amphetamine significantly decreased reaction time, improved accuracy, and reduced the latency of the P300 component relative to placebo, while having no effect on the N200 component. d-methamphetamine had no effect on reaction time, accuracy or the P300 component, but reduced the amplitude of the N200 component, relative to placebo. It was concluded that there is tentative support to suggest that d-amphetamine at a dose of 0.42 mg/kg may enhance speed of information processing while d-methamphetamine at a dose of 0.42 mg/kg may reflect changes to stimulus evaluation.

  10. Urinary pharmacokinetics of methamphetamine and its metabolite, amphetamine following controlled oral administration to humans.

    PubMed

    Kim, Insook; Oyler, Jonathan M; Moolchan, Eric T; Cone, Edward J; Huestis, Marilyn A

    2004-12-01

    Methamphetamine is widely abused for its euphoric effects. Our objectives were to characterize the urinary pharmacokinetics of methamphetamine and amphetamine after controlled methamphetamine administration to humans and to improve the interpretation of urine drug test results. Participants (n = 8) received 4 daily 10-mg (low) oral doses of sustained-release (d)-methamphetamine hydrochloride within 7 days. After 4 weeks, 5 participants received 4 daily 20-mg (high) oral doses. All urine specimens were collected during the study. Methamphetamine and amphetamine were measured by GC-MS/PCI. Maximum excretion rates ranged from 403 to 4919 microg/h for methamphetamine and 59 to 735 microg/h for amphetamine with no relationship between dose and excretion rate. The mean molar percentage of dose in the urine as total methamphetamine and amphetamine were 57.5 +/- 21.7% (low dose) and 40.9 +/- 8.5% (high dose). Mean urinary terminal elimination half-lives across doses were 23.6 +/- 6.6 hours for methamphetamine and 20.7 +/- 7.3 hours for amphetamine. Methamphetamine renal clearance across doses was 175 +/- 102 mL/min. The mean amphetamine/methamphetamine percentage ratio based on the area under the urinary excretion-time curve increased over time from 13.4 +/- 6.5% to 35.7 +/- 26.6%. Slow urinary excretion results in drug accumulation and increases in detection time windows. Our findings also support the presence of an active renal excretion mechanism for methamphetamine.

  11. HIV risk-taking behaviour among amphetamine users in Sydney, Australia.

    PubMed

    Hando, J; Hall, W

    1994-01-01

    A survey was undertaken of needle-sharing and sexually risky behaviour among 231 Australian amphetamine users, half of whom usually injected amphetamine. The prevalence of risky needle use and sexual behaviour was similar to that observed in recent Australian surveys of opioid injectors. About a third of those who had ever injected had shared needles, and the variables that best predicted frequency of sharing needles were having an injecting drug user as a partner, having experienced symptoms of dependence on amphetamines, and having sought medical treatment for an amphetamine related problem. Regular condom use with either regular or causal partners was low; only the minority employed in the sex industry regularly used condoms. Sexual risk-taking was not related to needle-sharing or amphetamine use. Although Australian amphetamine and opioid users have reduced their risks of transmitting HIV, there remains a substantial minority of both types of drug injector who continue to place themselves and others at risk by sharing needles and engaging in unsafe sexual behaviour.

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

    PubMed

    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.

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

    PubMed

    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.

  14. Alcohol use disorder

    MedlinePlus

    ... Alcohol abuse; Problem drinking; Drinking problem; Alcohol addiction; Alcoholism - alcohol use; Substance use - alcohol ... The National Institute on Alcohol Abuse and Alcoholism ... 1 drink per day Men should not drink more than 2 drinks per day

  15. Low dose acute alcohol effects on GABAA receptor subtypes

    PubMed Central

    Wallner, Martin; Hanchar, H. Jacob; Olsen, Richard W.

    2010-01-01

    GABAA receptors (GABAARs) are the main inhibitory neurotransmitter receptors and have long been implicated in mediating at least part of the acute actions of ethanol. For example, ethanol and GABAergic drugs including barbiturates and benzodiazepines share many pharmacological properties. Besides the prototypical synaptic GABAAR subtypes, nonsynaptic GABAARs have recently emerged as important regulators of neuronal excitability. While high doses (≥100 mM) of ethanol have been reported to enhance activity of most GABAAR subtypes, most abundant synaptic GABAARs are essentially insensitive to ethanol concentrations that occur during social ethanol consumption (<30 mM). However, extrasynaptic δ and β3 subunit-containing GABAARs, associated in the brain with α4or α6 subunits, are sensitive to low millimolar ethanol concentrations, as produced by drinking half a glass of wine. Additionally, we found that a mutation in the cerebellar α6 subunit (α6R100Q), initially reported in rats selectively bred for increased alcohol sensitivity, is sufficient to produce increased alcohol-induced motor impairment and further increases of alcohol sensitivity in recombinant α6β3δ receptors. Furthermore, the behavioral alcohol antagonist Ro15-4513 blocks the low dose alcohol enhancement on α4/6/β3δ receptors, without reducing GABA-induced currents. In binding assays α4β3δ GABAARs bind [3H] Ro15-4513 with high affinity, and this binding is inhibited, in an apparently competitive fashion, by low ethanol concentrations, as well as analogs of Ro15-4513 that are active to antagonize ethanol or Ro15-4513’s block of ethanol. We conclude that most low to moderate dose alcohol effects are mediated by alcohol actions on alcohol/Ro15-4513 binding sites on GABAAR subtypes. PMID:16814864

  16. The role of regional nerve block anesthesia for carotid endarterectomy: an experimental comparison with previous series with the use of general anesthesia and barbiturates for cerebral protection.

    PubMed

    Agrifoglio, G; Agus, G B; Bonalumi, F; Costantini, A; Carlesi, R

    1987-01-01

    A retrospective analysis was performed on a consecutive series of 60 cases divided into two groups given carotid endarterectomy (C.E.) for atherosclerotic disease. In the first group general anesthesia and barbiturate cerebral protection were employed; in group two, loco-regional anesthesia. Indications and risk factors were similar in the two groups; the surgical procedure was identical. The differences in the results are reported and factors contributing to cerebral protection or reduction in the risk of stroke are analyzed. The analysis indicates that loco-regional anesthesia for C.E. is a reliable method for detecting cerebral ischemia and guaranteeing cerebral protection by means of a temporary shunt when strictly necessary. PMID:3450753

  17. Formation of C═C bond via knoevenagel reaction between aromatic aldehyde and barbituric acid at liquid/HOPG and vapor/HOPG interfaces.

    PubMed

    Geng, Yanfang; Dai, Hongliang; Chang, Shaoqing; Hu, Fangyun; Zeng, Qingdao; Wang, Chen

    2015-03-01

    Controlling chemical reactions on surface is of great importance to constructing self-assembled covalent nanostructures. Herein, Knoevenagel reaction between aromatic aldehyde compound 2,5-di(5-aldehyde-2-thienyl)-1,4-dioctyloxybenzene (PT2) and barbituric acid (BA) has been successfully performed for the first time at liquid/HOPG interface and vapor/HOPG interface. The resulting surface nanostructures and the formation of C═C bond are recorded through scanning tunneling microscopy (STM), and confirmed by attenuated total reflectance Fourier-transform infrared (ATR/FT-IR) spectrometer and UV-vis absorption. The obtained results reveal that Knoevenagel condensation reaction can efficiently occur at both interfaces. This surface reaction would be an important step toward further reaction to produce innovative conjugated nanomaterial on the surface.

  18. Incentive sensitization by previous amphetamine exposure: increased cue-triggered "wanting" for sucrose reward.

    PubMed

    Wyvell, C L; Berridge, K C

    2001-10-01

    We reported previously that an amphetamine microinjection into the nucleus accumbens enables Pavlovian reward cues in a conditioned incentive paradigm to trigger excessive instrumental pursuit. Here we show that sensitization caused by previous amphetamine administration also causes reward cues to trigger excessive pursuit of their associated reward, even when sensitized rats are tested in a drug-free state. Rats learned to lever press for sucrose pellets, and they separately learned to associate sucrose pellets with Pavlovian cues (30 sec auditory cues). Amphetamine sensitization was induced by six daily injections of amphetamine (3 mg/kg, i.p.; controls received saline). Rats were tested for lever pressing under extinction conditions 10 d later, after a bilateral microinjection of intra-accumbens vehicle or amphetamine (5 microg/0.5 microl per side). Cue-triggered pursuit of sucrose reward was assessed by increases in pressing on the sucrose-associated lever during intermittent presentations of a free conditioned stimulus (CS+) sucrose cue. Sensitized rats pressed at normal levels during baseline and during the CS-, but the CS+ triggered 100% greater increases in pressing from sensitized rats than from control rats after vehicle microinjection. Sensitization therefore enhanced the incentive salience attributed to the CS+ even when rats were tested while drug-free. For control rats, a microinjection of intra-accumbens amphetamine was needed to produce the same enhancement of cue-triggered reward "wanting." The amphetamine microinjection also interacted synergistically in sensitized rats to produce intrusive cue-triggered pursuit behaviors (e.g., investigatory sniffing) that interfered with goal-directed lever pressing. These results support the incentive-sensitization theory postulate that sensitization causes excessive cue-triggered "wanting" for an associated reward.

  19. Deposition characteristics of methamphetamine and amphetamine in fingernail clippings and hair sections.

    PubMed

    Lin, Dong-Liang; Yin, Rea-Ming; Liu, Hsiu-Chuan; Wang, Chung-Yi; Liu, Ray H

    2004-09-01

    Fingernail clippings collected from 97 consenting females, who admitted amphetamines and/or opiates use and are currently under treatment, were quantitatively analyzed for the presence of methamphetamine and amphetamine. Sixty-two subjects were found positive for methamphetamine/amphetamine. Paired nail-hair specimens were collected from 6 of these subjects for a 12-week period and analyzed to determine the duration of detectability and deposition characteristics of amphetamines in fingernails; whether data derived from the analysis of nail clippings and hair sections are reflective of drug use patterns; and whether there is a relationship between the analytical data derived from the paired nail-hair specimens. Typical sample pre-treatment procedures and GC-MS protocols were evaluated to establish the validity of various analytical parameters and to ensure that the resulting data can be properly interpreted. Major findings include 1. Methamphetamine was found in the nails of 62 subjects collected in Week 0. The distribution of methamphetamine concentrations (ng/mg) in these nail samples are range, 0.46-61.50; mean, 9.96; and standard deviation: 13.33. The corresponding data for amphetamine are < 0.20-5.42, 0.93, and 1.01, respectively. 2. Sectional analyses of hair samples collected from 6 subjects in Week 0 show methamphetamine concentrations peak at different distances from the root. 3. The concentrations of methamphetamine and amphetamine in nail clippings are generally lower than the first 1.5-cm section of hair samples collected at the same time from the same individual. 4. Amphetamine/ methamphetamine concentration ratios in nail clippings and hair samples are comparable. 5. Methamphetamine concentration in the nail clippings collected at Weeks 0, 4, 8, and 12 decreases in a pattern similar to that exhibited by the first 1.5-cm sections of the hair samples collected at the same time.

  20. Stress-induced changes in mood and cortisol release predict mood effects of amphetamine

    PubMed Central

    Hamidovic, Ajna; Childs, Emma; Conrad, Megan; King, Andrea; de Wit, Harriet

    2010-01-01

    Background Stress is thought to contribute to both initiation and relapse to drug abuse. However, the mechanisms by which stress influences drug use are unclear. Interestingly, responses to acute administration of stimulant drugs resemble certain neuronal and hormonal responses to acute stress, and there is accumulating evidence that individual variation in the positive reinforcing or euphorigenic effects of a drug are related to individual differences in responsivity to acute stress. Methods In this study we evaluated relationships between physiological and subjective responses to a stressful task and to an oral dose of d-amphetamine in healthy adult volunteers (N=34). Individuals participated in four experimental sessions; two behavioral sessions involving a stressful task (i.e. public speech) or a non-stressful control task, and two drug sessions involving oral administration of d-amphetamine (20mg) or a placebo. The dependent measures included salivary cortisol, heart rate, mean arterial pressure, and subjective ratings of mood. Results As expected, both stress and d-amphetamine increased cortisol, heart rate and blood pressure. Stress increased negative mood, whereas d-amphetamine induced prototypic stimulant effects and increased ratings of drug liking. Analyses revealed that increased negative mood states after stress were correlated with positive mood after amphetamine. In addition, increased cortisol after stress was correlated with positive mood responses to amphetamine. Finally, there were modest positive correlations between cortisol and heart rate increases after stress and mean arterial pressure after amphetamine. Conclusions These results support and extend previous observations that responses to acute stress are correlated with certain subjective, hormonal and cardiovascular effects of a stimulant drug. PMID:20176450

  1. Distribution of methamphetamine and amphetamine in drug abusers' head hair.

    PubMed

    Lee, Sooyeun; Han, Eunyoung; Park, Yonghoon; Choi, Hwakyung; Chung, Heesun

    2009-09-10

    In order to aid the interpretation of hair results from methamphetamine (MA) abusers the MA and amphetamine (AP) concentrations in 2070 hair samples were statistically evaluated. The MA and AP concentrations in hair were put into three groups arbitrarily representing low, medium and high ranges and the metabolite-to-parent drug ratios of each group were examined. The concentration ranges proposed here were also applied to the interpretation of five authentic cases. The low, medium and high ranges of MA were 0.5-4.2, 4.2-24.5 and 24.5-608.9 ng/mg and those of AP were 0.1-0.4, 0.4-1.7 and 1.7-41.4 ng/mg. The AP-to-MA ratios showed large variation but a tendency that it decreased as the MA ranges increased. This evaluation was very useful to presume the severity of individuals' MA abuse and to provide law enforcement agencies more understandable information. It could also facilitate the court's decision regarding specific circumstances surrounding the drug-related crimes.

  2. Amphetamine-Enhanced Motor Training after Cervical Contusion Injury

    PubMed Central

    Krisa, Laura; Frederick, Kelly L.; Canver, John C.; Stackhouse, Scott K.; Shumsky, Jed S.

    2012-01-01

    Abstract Individually, motor training, pharmacological interventions, and housing animals in an enriched environment (EE) following spinal cord injury (SCI) result in limited functional improvement but, when combined, may enhance motor function. Here, we tested amphetamine (AMPH)-enhanced skilled motor training following a unilateral C3–C4 contusion injury on the qualitative components of reaching and on skilled forelimb function, as assessed using single-pellet and staircase reaching tasks. Kinematic analysis evaluated the quality of the reach, and unskilled locomotor function was also tested. Animals receiving AMPH and skilled forelimb training performed better than operated control animals on qualitative reaching, but not on skilled reaching. Those that received the combination treatment and were housed in EE cages showed significantly less improvement in qualitative reaching and grasping. Kinematic analysis revealed a decrease in digit abduction during skilled reaching among all groups, with no differences among groups. Kinematics provided no evidence that improved function was related to improved quality of reach. There was no evidence of neuroprotection in the cervical spinal cord. The absence of evidence for kinematic improvement or neuroprotection suggested that AMPH-enhanced motor training is due primarily to supraspinal effects, an enhancement of attention during skilled motor training, or plasticity in supraspinal circuitry involved with motor control. PMID:21651384

  3. Influence of amphetamine on recovery after intracerebral hemorrhage in rats.

    PubMed

    Auriat, Angela M; Colbourne, Frederick

    2008-01-25

    D-amphetamine (AMP) paired with physical activity (e.g., beam walking) improves recovery after ischemic injury to the cortical motor system of rodents. We tested whether AMP promotes recovery after intracerebral hemorrhage (ICH) in rats. A moderate-sized ICH was produced by stereotaxically injecting collagenase into the striatum. Five days later rats were placed into either environmental enrichment cages (EE) or a control condition (group housing in standard cages) until euthanasia at 4 weeks post-ICH. Animals were injected with either AMP (2 mg/kg i.p.) or sterile saline on days 7, 9 and 11 after ICH. Rats in EE also received training on beam (walking) and tray (skilled reaching) tasks 30 min after each injection. Walking (beam and ladder task), skilled reaching (tray and staircase tasks) and neurological deficits (NDS) were repeatedly assessed. We predicted that EE would improve recovery and that AMP would further enhance it. Results showed that EE, but not AMP, significantly and consistently improved recovery on the beam and ladder task. Neither treatment significantly affected skilled reaching. Lesion volume was not significantly different among groups (overall average: 44.6 mm(3) of tissue lost +/-15.3 S.D.). In conclusion, EE provides modest benefit for striatal ICH whereas AMP does not. This suggests that AMP will not provide substantial benefit to those patients with severe ICH affecting the basal ganglia. PMID:17904232

  4. Rats showing low and high sensitization of frequency-modulated 50-kHz vocalization response to amphetamine differ in amphetamine-induced brain Fos expression.

    PubMed

    Kaniuga, Ewelina; Taracha, Ewa; Stępień, Tomasz; Wierzba-Bobrowicz, Teresa; Płaźnik, Adam; Chrapusta, Stanisław J

    2016-10-01

    Individuals predisposed to addiction constitute a minority of drug users, in both humans and animal models of the disorder, but there are no established characteristics that would allow identifying them beforehand. Our studies demonstrate that sensitization of rat 50-kHz ultrasonic vocalization (USV) response to amphetamine shows marked inter-individual diversity but substantial intra-individual stability. Low sensitization of the response shows relevance to the acquisition of self-administration of this drug and hence might be of predictive value regarding the risk of addiction. We compared amphetamine-induced Fos expression in 16 brain regions considered important for the development of addiction between rats preselected for low and high sensitization of the response and next given nine daily amphetamine doses followed by a 2-week withdrawal and final amphetamine challenge. Ventral tegmental area and nucleus accumbens shell Fos-positive nuclei counts correlated positively with 50-kHz USV response to the challenge in high-sensitized rats. Compared to those in amphetamine-untreated controls, Fos-positive nuclei counts were significantly and markedly (2-6 times) higher in 12 regions in high-sensitized rats, whereas in low-sensitized rats they were significantly higher in the cingulate cortex and dorsomedial striatum only. The difference in the counts between the latter two subsets reached statistical significance in dorsomedial and dorsolateral striatum and three out of four cortical regions studied. The fact that the diversification was most distinct in dorsal striatum that plays a critical role in the transition from controlled to compulsive drug intake suggests that the USV-based categorization may be related to divergent vulnerability of rats to AMPH addiction. PMID:27507424

  5. NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines.

    PubMed

    2005-07-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for amphetamines to cause adverse effects on reproduction and development in humans. Amphetamines evaluated were D- and D,L-amphetamine and methamphetamine. Amphetamine is approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD) in persons over 3 years of age and narcolepsy; methamphetamine is approved for the treatment of ADHD in persons 6 years of age and older and for short-term treatment of obesity. Amphetamines were selected for evaluation because of 1) widespread usage in children, 2) availability of developmental studies in children and experimental animals, and 3) public concern about the effect of this stimulant on child development. The results of this evaluation on amphetamines are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Methylphenidate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to methylphenidate on human development and reproduction. First, there is some concern for developmental effects, specifically for potential neurobehavioral alterations, from prenatal amphetamine exposure in humans both in therapeutic and non-therapeutic settings. After prenatal exposure to therapeutic doses of amphetamine, rat pups demonstrated neurobehavioral alterations. Data from human and animal studies were judged insufficient for an evaluation of the effect of amphetamine exposure on growth and other related developmental effects. Second, there is concern for methamphetamine-induced adverse developmental effects, specifically on growth and neurobehavioral development, in therapeutic and non-therapeutic settings. This conclusion is based

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2016-06-01

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

  8. The anorexigenic peptide cocaine-and-amphetamine-regulated transcript modulates rem-sleep in rats.

    PubMed

    Méndez-Díaz, M; Domínguez Martín, E; Pérez Morales, M; Ruiz-Contreras, A E; Navarro, L; Prospéro-García, O

    2009-12-01

    It is known that the sleep-waking cycle is modulated by several molecules that may also regulate food intake, among them several neuropeptides. The cocaine-and-amphetamine-regulated transcript has been studied in relation to food ingestion, but it seems to have several other functions that may include sleep regulation. In this context, we studied the effect of the intracerebroventricular administration of the cocaine-and-amphetamine-regulated transcript (0.15, 0.3, 0.6, 0.9nmol) on the sleep-waking cycle (12-h recordings), as well as its effect on food intake in rats. Additionally, we analyzed the neuronal activity as measured by c-Fos expression induced by the cocaine-and-amphetamine-regulated transcript in neurons of nuclei involved in the regulation of sleep and feeding behavior. Our main finding is that 0.3nmol of the cocaine-and-amphetamine-regulated transcript increases rapid-eye-movement sleep. In addition, our results further support that this neuropeptide triggers satiety; c-Fos expression suggested that the cocaine-and-amphetamine-regulated transcript activates specific hypothalamic nuclei without affecting other brain structures known to be involved in sleep regulation. These data further support the notion that a few neuropeptides are involved in the regulation of both the sleep-waking and the hunger-satiety cycles.

  9. The Relative Reinforcing Strength of Methamphetamine and d-Amphetamine in Monkeys Self-Administering Cocaine

    PubMed Central

    Lile, Joshua A.; Charnigo, Richard J.; Nader, Michael A.

    2013-01-01

    Epidemiological data indicate that rates of methamphetamine misuse surpass those of d-amphetamine, but self-administration research in animals and humans has not typically demonstrated differences in their reinforcing effects. The present study used a within-session, exponentially-increasing progressive-ratio schedule and extended-access conditions to assess the relative reinforcing strength of d-amphetamine and methamphetamine in rhesus monkeys (n=5) trained to self-administer cocaine. A range of doses of methamphetamine (0.003–0.1 mg/kg/injection), d-amphetamine (0.003–0.1 mg/kg/injection) and cocaine (0.003–0.3 mg/kg/injection) was tested to capture the ascending and descending limbs of the dose-effect functions. Each drug functioned as a reinforcer, but the peak number of self-administered d-amphetamine injections was significantly lower compared to methamphetamine and cocaine; the peak number of self-administered injections of cocaine and methamphetamine did not differ. Although differences in availability and other social factors likely impact relative rates of abuse, the present data suggest that the greater reinforcing strength of methamphetamine contributes to its increased use compared to d-amphetamine. PMID:23907377

  10. Caffeine and amphetamine produce cross-sensitization to nicotine-induced locomotor activity in mice.

    PubMed

    Celik, Eylem; Uzbay, I Tayfun; Karakas, Sirel

    2006-01-01

    Sensitization development is linked to the addictive potential of the drugs. The same mechanisms might play a role in sensitization development to the different addictive drugs. The aim of the study was to investigate the development of cross-sensitization to caffeine and amphetamine in nicotine-induced locomotor sensitization in mice. Caffeine (2.5-20 mg/kg), amphetamine (1-16 mg/kg) or saline were injected to Swiss-Webster mice and locomotor activity was recorded for 30 min. Nicotine (0.5-2 mg/kg) or saline were injected to mice and locomotor activity was recorded for 30 min. Process was applied for 19 days, every other day (10 sessions). Caffeine (5 mg/kg), amphetamine (4 mg/kg) or saline were challenged to the different groups of nicotine-sensitized mice 2 days later on the last nicotine injection, and locomotor activity was recorded. Repetitive injections of nicotine (0.5-2 mg) produced locomotor sensitization in mice. After caffeine and amphetamine challenge injections, locomotor activity of the nicotine-sensitized mice was found to be significantly higher than saline-pretreated mice. Saline challenge did not produce any significant effect in nicotine- or saline-pretreated mice. Our results suggest that a cross-sensitization developed to both caffeine and amphetamine in nicotine-sensitized mice. In conclusion, similar central mechanisms may be responsible for the development of addiction to these substances.

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

    SciTech Connect

    Daniel, D.G.; Weinberger, D.R.; Jones, D.W.; Zigun, J.R.; Coppola, R.; Handel, S.; Bigelow, L.B.; Goldberg, T.E.; Berman, K.F.; Kleinman, J.E. )

    1991-07-01

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

  12. The relative reinforcing strength of methamphetamine and D-amphetamine in monkeys self-administering cocaine.

    PubMed

    Lile, Joshua A; Charnigo, Richard J; Nader, Michael A

    2013-09-01

    Epidemiological data indicate that rates of methamphetamine misuse surpass those of D-amphetamine, but self-administration research in animals and humans has not typically demonstrated differences in their reinforcing effects. The present study used a within-session, exponentially increasing progressive-ratio schedule and extended-access conditions to assess the relative reinforcing strength of D-amphetamine and methamphetamine in rhesus monkeys (n=5) trained to self-administer cocaine. A range of doses of methamphetamine (0.003-0.1 mg/kg/injection), D-amphetamine (0.003-0.1 mg/kg/injection), and cocaine (0.003-0.3 mg/kg/injection) was tested to capture the ascending and descending limbs of the dose-effect functions. Each drug functioned as a reinforcer, but the peak number of self-administered D-amphetamine injections was significantly lower compared with methamphetamine and cocaine; the peak number of self-administered injections of cocaine and methamphetamine did not differ. Although differences in availability and other social factors likely impact relative rates of abuse, the present data suggest that the greater reinforcing strength of methamphetamine contributes to its increased use compared with D-amphetamine.

  13. Pleiotrophin gene transcription in the rat nucleus accumbens is stimulated by an acute dose of amphetamine.

    PubMed

    Le Grevès, Pierre

    2005-05-30

    Pleiotrophin (PTN) is a heparin-binding protein with diverse functions. For example, it stimulates neurite outgrowth, mitogenesis, repair and differentiation, effects that are similar to those of the neurotrophins. The neurotrophins have, in recent years, been implicated as mediators of structural plasticity, suggested to underlie the development of behavioural sensitisation to many drugs of abuse. Since NMDA receptor antagonists inhibit the underlying morphological changes, the mechanisms are thought to be highly dependent on the activation of the NMDA subtype of glutamate receptors. To investigate if PTN has a possible role in structural plasticity, its responsiveness to an acute dose of amphetamine was studied. Amphetamine is a well-characterised inducer of sensitisation. A group of rats was systemically treated with amphetamine (10 mg/kg) and the effect on the PTN gene transcription was studied 4 h later. A separate group of rats was pretreated with the NMDA receptor antagonist MK-801 (0.25 mg/kg) 30 min prior to the administration of amphetamine. Northern blot analysis revealed a significant increase of the PTN transcript after the administration of amphetamine. However, MK-801 pretreatment did not block this effect; in contrast, it further increased PTN mRNA levels. As the response to the two drugs resembles the one earlier reported on the gene expression of brain-derived neurotrophic factor (BDNF), the present results suggest that PTN may be an attractive protein to study further in the field of synaptic plasticity.

  14. Progression of Cellular Adaptations in Medial Prefrontal and Orbitofrontal Cortex in Response to Repeated Amphetamine

    PubMed Central

    Homayoun, Houman; Moghaddam, Bita

    2010-01-01

    Recent theories on addiction implicate adaptive changes in prefrontal cortex (PFC) neurons in reinforcing and psychotomimetic properties of psychostimulants, yet little is known about how neuronal responses to these drugs change over time. Here we describe electrophysiological evidence for a progressive and sustained change in the response of PFC neurons to amphetamine during repeated exposure. In spontaneously behaving rats and in rats engaged in an instrumental responding task, we followed the activity of medial PFC (mPFC) and orbitofrontal cortex (OFC) neurons during daily exposure to amphetamine and after a post-withdrawal challenge. Repeated amphetamine increased the number of responsive neurons and the magnitude of responses and modified spontaneous burst patterns. These changes were apparent after a few exposures to amphetamine, were amplified after withdrawal, and were region specific in that repeated amphetamine increasingly produced inhibitory responses in mPFC and excitatory responses in OFC. In behaviorally engaged animals, the gradual enhancement in mPFC inhibition and OFC overactivation correlated with a progressive impairment of instrumental responding. Furthermore, these changes were evident predominately in neurons that displayed phasic responses during task-related events. These rapid-onset and sustained cellular adaptations suggest that even limited exposure to psychostimulants may reduce the influence of mPFC neurons on behavior while at the same time exaggerating information encoded by OFC neurons. PMID:16885216

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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. PMID:27418423

  18. The relative reinforcing strength of methamphetamine and D-amphetamine in monkeys self-administering cocaine.

    PubMed

    Lile, Joshua A; Charnigo, Richard J; Nader, Michael A

    2013-09-01

    Epidemiological data indicate that rates of methamphetamine misuse surpass those of D-amphetamine, but self-administration research in animals and humans has not typically demonstrated differences in their reinforcing effects. The present study used a within-session, exponentially increasing progressive-ratio schedule and extended-access conditions to assess the relative reinforcing strength of D-amphetamine and methamphetamine in rhesus monkeys (n=5) trained to self-administer cocaine. A range of doses of methamphetamine (0.003-0.1 mg/kg/injection), D-amphetamine (0.003-0.1 mg/kg/injection), and cocaine (0.003-0.3 mg/kg/injection) was tested to capture the ascending and descending limbs of the dose-effect functions. Each drug functioned as a reinforcer, but the peak number of self-administered D-amphetamine injections was significantly lower compared with methamphetamine and cocaine; the peak number of self-administered injections of cocaine and methamphetamine did not differ. Although differences in availability and other social factors likely impact relative rates of abuse, the present data suggest that the greater reinforcing strength of methamphetamine contributes to its increased use compared with D-amphetamine. PMID:23907377

  19. Overview of Alcohol Consumption

    MedlinePlus

    ... Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol ... other questions about alcohol. Here’s what we know: Alcohol’s effects vary from person to person, depending on a ...

  20. Alcohol and pregnancy

    MedlinePlus

    Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... When a pregnant woman drinks alcohol, the alcohol travels through her blood and into the baby's blood, tissues, and organs. Alcohol breaks down much more slowly in ...

  1. Amphetamine paradoxically augments exocytotic dopamine release and phasic dopamine signals.

    PubMed

    Daberkow, D P; Brown, H D; Bunner, K D; Kraniotis, S A; Doellman, M A; Ragozzino, M E; Garris, P A; Roitman, M F

    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 nonexocytotic 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 2 h. 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, nonelectrically evoked, phasic increases in extracellular dopamine. Finally, using an operant sugar reward paradigm, we showed that low-dose AMPH augmented dopamine transients elicited by sugar-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 upregulation 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

  2. Biphasic mechanisms of amphetamine action at the dopamine terminal.

    PubMed

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

    2014-04-16

    In light of recent studies suggesting that amphetamine (AMPH) increases electrically evoked dopamine release ([DA]o), we examined discrepancies between these findings and literature that has demonstrated AMPH-induced decreases in [DA]o. The current study has expanded the inventory of AMPH actions by defining two separate mechanisms of AMPH effects on [DA]o at high and low doses, one dopamine transporter (DAT) independent and one DAT dependent, respectively. AMPH concentrations were measured via microdialysis in rat nucleus accumbens after intraperitoneal injections of 1 and 10 mg/kg and yielded values of ∼10 and 200 nM, respectively. Subsequently, voltammetry in brain slices was used to examine the effects of low (10 nM), moderate (100 nM), and high (10 μM) concentrations of AMPH across a range of frequency stimulations (one pulse; five pulses, 20 Hz; 24 pulses, 60 Hz). We discovered biphasic, concentration-dependent effects in WT mice, in which AMPH increased [DA]o at low concentrations and decreased [DA]o at high concentrations across all stimulation types. However, in slices from DAT-KO mice, [DA]o was decreased by all concentrations of AMPH, demonstrating that AMPH-induced increases in [DA]o are DAT dependent, whereas the decreases at high concentrations are DAT independent. We propose that low AMPH concentrations are insufficient to disrupt vesicular sequestration, and therefore AMPH acts solely as a DAT inhibitor to increase [DA]o. When AMPH concentrations are high, the added mechanism of vesicular depletion leads to reduced [DA]o. The biphasic mechanisms observed here confirm and extend the traditional actions of AMPH, but do not support mechanisms involving increased exocytotic release.

  3. Regulation of dopamine transporter trafficking by intracellular amphetamine.

    PubMed

    Kahlig, Kristopher M; Lute, Brandon J; Wei, Yuqiang; Loland, Claus J; Gether, Ulrik; Javitch, Jonathan A; Galli, Aurelio

    2006-08-01

    The dopamine (DA) transporter (DAT) mediates the removal of released DA. DAT is the major molecular target responsible for the rewarding properties and abuse potential of the psychostimulant amphetamine (AMPH). AMPH has been shown to reduce the number of DATs at the cell surface, and this AMPH-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-hDAT. Furthermore, direct intracellular application of AMPH, via a whole-cell patch pipette, stimulated the trafficking of Y335A-hDAT. Taken together, these data suggest that the DAT transport cycle is not required for AMPH-induced down-regulation and that an increase of intracellular AMPH is an essential component of DAT redistribution.

  4. Exercise modifies amphetamine relapse: behavioral and oxidative markers in rats.

    PubMed

    Segat, H J; Kronbauer, M; Roversi, Kr; Schuster, A J; Vey, L T; Roversi, K; Pase, C S; Antoniazzi, C T D; Burger, M E

    2014-04-01

    Exercise has been reported to attenuate rewarding symptoms related to addictive drugs mainly by affecting the brain neuroplasticity and neurotransmission. In this study, we investigated the influence of physical exercise on the behavioral and enzymatic status related to drug relapse in rats. Animals were primarily treated with amphetamine (AMPH; 4.0 mg/kg, i.p.) or vehicle (C; NaCl 0.9% solution) in the conditioned place preference (CPP) paradigm for 14 days. Half of each experimental group was then submitted to swimming sessions (60 min/day, 5 days/week) for 5 weeks. Animals were re-exposed to AMPH- or vehicle-CPP paradigm for another 3 days, in order to observe drug relapse and anxiety-like symptoms, which were observed 24h after AMPH reconditioning in CPP, and elevated plus maze (EPM), respectively, and brain biochemical evaluations were carried out subsequently. While AMPH was related to place preference and anxiety, indicating drug addiction and abstinence symptoms, respectively, physical activity was able to prevent relapse symptoms after AMPH reconditioning, as observed through consecutive decreased CPP and anxiety-like symptoms. In addition, AMPH exposure increased reactive species (RS) generation and protein carbonyl (PC) levels together with decreased activity of catalase- and Na(+)K(+)-ATPase in hippocampus. On the other hand, while all AMPH-induced effects were prevented by physical activity, there was a negative correlation between PC levels (r=0.65; p<0.003) and CAT activity, and a positive correlation between RS generation and PC levels (r=0.54; r=0.52, p<0.05) with AMPH-CPP after exercise. These results indicate that exercise has a clear beneficial influence on the prevention of psychostimulant drug relapse.

  5. Enhancement of Auditory Fear Conditioning after Housing in a Complex Environment Is Attenuated by Prior Treatment with Amphetamine

    ERIC Educational Resources Information Center

    Briand, Lisa A.; Robinson, Terry E.; Maren, Stephen

    2005-01-01

    Prior exposure to drugs of abuse has been shown to occlude the structural plasticity associated with living in a complex environment. Amphetamine treatment may also occlude some cognitive advantages normally associated with living in a complex environment. To test this hypothesis we examined the influence of prior exposure to amphetamine on fear…

  6. Effects of Amphetamine-CNS Depressant Combinations and of Other CNS Stimulants in Four-Choice Drug Discriminations

    ERIC Educational Resources Information Center

    Li, Mi; Wessinger, William D.; McMillan, D. E.

    2005-01-01

    Three pigeons were trained to discriminate among 5 mg/kg pentobarbital, 2 mg/kg amphetamine, a combination of these two drugs at these doses, and saline using a four-choice procedure (amphetamine--pentobarbital group). Three other pigeons were trained to discriminate among 5 mg/kg morphine, 2 mg/kg methamphetamine, a combination of these two drugs…

  7. The effects of paradoxical sleep deprivation on amphetamine-induced behavioral sensitization in adult and adolescent mice.

    PubMed

    Kameda, Sonia R; Fukushiro, Daniela F; Trombin, Thaís F; Sanday, Leandro; Wuo-Silva, Raphael; Saito, Luis P; Tufik, Sergio; D'Almeida, Vânia; Frussa-Filho, Roberto

    2014-08-30

    Drug-induced behavioral sensitization (BS), paradoxical sleep deprivation (PSD) and adolescence in rodents are associated with changes in the mesolimbic dopaminergic system. We compared the effects of PSD on amphetamine-induced BS in adult and adolescent mice. Adult (90 days old) and adolescent (45 days old) Swiss mice were subjected to PSD for 48h. Immediately after PSD, mice received saline or 2.0mg/kg amphetamine intraperitoneally (i.p.), and their locomotion was quantified in activity chambers. Seven days later, all the animals were challenged with 2.0mg/kg amphetamine i.p., and their locomotion was quantified again. Acute amphetamine enhanced locomotion in both adult and adolescent mice, but BS was observed only in adolescent mice. Immediately after its termination, PSD decreased locomotion of both saline- and amphetamine-treated adolescent mice. Seven days later, previous PSD potentiated both the acute stimulatory effect of amphetamine and its sensitization in adolescent mice. In adult animals, previous PSD revealed BS. Our data suggest that adolescent mice are more vulnerable to both the immediate and long-term effects of PSD on amphetamine-induced locomotion. Because drug-induced BS in rodents shares neuroplastic changes with drug craving in humans, our findings also suggest that both adolescence and PSD could facilitate craving-related mechanisms in amphetamine abuse.

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

    PubMed

    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.

  9. Some effects of chlordiazepoxide and d-amphetamine on response force during punished responding in rats.

    PubMed

    Fowler, S C; Price, A W

    1978-03-01

    Rats were reinforced with water on a continuous reinforcement schedule and were also punished with electric shock for every fifth response applied to a silent, isometric, force-sensing manipulandum. Oral doses of chlordiazepoxide (3.0, 9.0, 27.0 mg/kg) increased both conventional rate and force of punished responding. In contrast, d-amphetamine (0.8, 1.6, 3.2 mg/kg, by gavage) further decreased conventional rate and force of response, but this latter drug increased the rate of recorded responses that were lower than the 15-g force criterion for response consequences. The results for chlordiazepoxide are viewed in terms of its anxiolytic properties, while the d-amphetamine data appear to support a theory of amphetamine effects based on the concept of stereotyped behaviors.

  10. Analysis of amphetamine and methamphetamine as emerging pollutants in wastewater and wastewater-impacted streams.

    PubMed

    Boles, Tammy H; Wells, Martha J M

    2010-04-16

    The identification and quantitation of the non-ecstasy amphetamine-type stimulants (ATSs) amphetamine and methamphetamine in lakes, rivers, wastewater treatment plant influents, effluents, and biosolids are reviewed. Neither monitoring nor reporting is required of these ATSs, which are considered emerging pollutants, but they have been identified in the environment. Amphetamine and methamphetamine enter our water supply by human excretion after legal or illegal consumption and via manufacturing in clandestine laboratories. Analytical methodology for sampling, sample preparation, separation, and detection of ATSs is discussed. Reported occurrences of ATSs in the environment and their use in municipal sewage epidemiology are noted. Future research needs that challenge applications of analytical techniques are discussed. The review focuses on research reported from 2004 to 2009.

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

    PubMed

    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. PMID:23767434

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Amphetamine accelerates recovery of locomotor function following bilateral frontal cortex ablation in cats.

    PubMed

    Sutton, R L; Hovda, D A; Feeney, D M

    1989-08-01

    Prior work has demonstrated that d-amphetamine hastens recovery of beam-walking ability following unilateral sensorimotor or frontal cortex ablation (Hovda & Feeney, 1984). In this study, after bilateral frontal cortex ablation, cats given injections of d-amphetamine showed an enduring acceleration of recovery of beam-walking ability relative to saline controls. In general, rates of spontaneous and drug-induced recovery in cats with bilateral lesions were similar to those previously reported for cats with unilateral ablations. These results indicate that the bilateral corticostriate and corticothalamic projections from the contralateral homotopic cortex do not mediate the beneficial effects of d-amphetamine on locomotor recovery after unilateral cortical ablation. PMID:2765187

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

    PubMed

    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.

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

    PubMed

    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-tetrahydrocannabinol.

  16. Reduction of amphetamine hydroxylamine and other aliphatic hydroxylamines by benzamidoxime reductase and human liver microsomes.

    PubMed

    Clement, B; Behrens, D; Möller, W; Cashman, J R

    2000-10-01

    For the reduction of N-hydroxylated derivatives of strongly basic functional groups, such as amidines, guanidines, and aminohydrazones, an oxygen-insensitive liver microsomal system, the benzamidoxime reductase, has been described. To reconstitute the complete activity of the benzamidoxime reductase, the system required cytochrome b(5), NADH-cytochrome b(5)-reductase, and the benzamidoxime reductase, a cytochrome P450 enzyme, which has been purified to homogeneity from pig liver. It was not known if this enzyme system was also capable of reducing aliphatic hydroxylamines. The N-hydroxylation of aliphatic amines is a well-known metabolic process. It was of interest to study the possibility of benzamidoxime reductase reducing N-hydroxylated metabolites of aliphatic amines back to the parent compound. Overall, N-hydroxylation and reduction would constitute a futile metabolic cycle. As examples of medicinally relevant compounds, the hydroxylamines of methamphetamine, amphetamine, and N-methylamine as model compounds were investigated. Formation of methamphetamine and amphetamine was analyzed by newly developed HPLC methods. All three hydroxylamines were easily reduced by benzamidoxime reductase to their parent amines with reduction rates of 220.6 nmol min(-1) (mg of protein)(-1) for methamphetamine, 5.25 nmol min(-1) (mg of protein)(-1) for amphetamine, and 153 nmol min(-1) (mg of protein)(-1) for N-methylhydroxylamine. Administration of synthetic hydroxylamines of amphetamine and methamphetamine to primary rat neuronal cultures produced frank cell toxicity. Compared with amphetamine or the oxime of amphetamine, the hydroxylamines were significantly more toxic to primary neuronal cells. The benzamidoxime reductase is therefore involved in the detoxication of these reactive hydroxylamines.

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

    PubMed

    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.

  18. Prolonged attenuation of the reinforcing strength of cocaine by chronic d-amphetamine in rhesus monkeys.

    PubMed

    Czoty, Paul W; Gould, Robert W; Martelle, Jennifer L; Nader, Michael A

    2011-01-01

    Chronic treatment with the indirect dopamine agonist d-amphetamine can reduce cocaine use in clinical trials and, in preclinical studies in laboratory animals, attenuates daily cocaine self-administration. The present study extended previous results to conditions designed to reflect a more clinically relevant experience of cocaine exposure and d-amphetamine treatment. Each morning, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio schedule of reinforcement. After determining a dose-response curve for cocaine (0.003-0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule of reinforcement in the evening, cocaine self-administration sessions were suspended and d-amphetamine (0.01-0.056 mg/kg/h, i.v.) was administered continuously for at least 24 days, except during cocaine self-administration sessions, which were conducted using the PR schedule once every 8 days. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was redetermined. Cocaine- and food-maintained responding were also examined after discontinuation of d-amphetamine. Although individual differences in sensitivity were observed, d-amphetamine produced selective, qualitatively similar decreases in the reinforcing strength of cocaine in all monkeys that persisted at least 4 weeks. Moreover, cocaine dose-effect curves were shifted downward and/or to the right. For 2 weeks following discontinuation of d-amphetamine treatment, the reinforcing strength of cocaine varied within and across individuals, however, on the whole no increased sensitivity was apparent. These data provide further support for the use of agonist medications for cocaine abuse, and extend the conditions under which such treatment is successful to those that incorporate clinically relevant patterns of cocaine use and drug treatment. PMID:20962765

  19. Amphetamine reward in food restricted mice lacking the melanin-concentrating hormone receptor-1.

    PubMed

    Geuzaine, Annabelle; Tyhon, Amélie; Grisar, Thierry; Brabant, Christian; Lakaye, Bernard; Tirelli, Ezio

    2014-04-01

    Chronic food restriction (FR) and maintenance of low body weight have long been known to increase the rewarding and motor-activating effects of addictive drugs. However, the neurobiological mechanisms through which FR potentiates drug reward remain largely unknown. Melanin-concentrating hormone (MCH) signaling could be one of these mechanisms since this peptide is involved in energy homeostasis and modulates mesolimbic dopaminergic transmission. The purpose of the present study was to test this hypothesis by investigating the impact of FR on amphetamine reward in wild-type (WT) and knockout mice lacking the melanin-concentrating hormone receptor-1 (MCHR1-KO). The rewarding effects of amphetamine (0.75-2.25 mg/kg, i.p.) were measured with the conditioned place preference (CPP) technique. The food of the mice was restricted to maintain their body weight at 80-85% of their free-feeding (FF) weight throughout the entire CPP experiment. Locomotor activity of the animals was recorded during the conditioning sessions. Our results show that locomotion of all the food-restricted mice treated with saline or amphetamine increased over the sessions whatever the genotype. On the place preference test, the amplitude of CPP induced by 0.75 mg/kg amphetamine was higher in food restricted WT mice than in free-fed WT mice and food restricted MCHR1-KO mice. However, FR did not affect amphetamine reward in MCHR1-KO mice. The present results indicate that MCH signaling could be involved in the ability of FR to increase amphetamine-induced CPP.

  20. Evaluation of the pharmacological similarities between phenylpropanolamine and amphetamine: effects on schedule-controlled behavior.

    PubMed

    Wagner, G C; Jarvis, M F

    1990-01-01

    In an effort to determine the degree to which the repeated administration of phenylpropanolamine (PPA) results in the development of tolerance to its disruptive effects on operant responding as well as cross-tolerance to the effects of acutely administered amphetamine, water-deprived rats were first trained on a fixed-ratio 5 (FR-5) schedule for water presentation. Dose-response curves for the effects of PPA and amphetamine (administered IP, 15 min presession) were then determined (ED50 = 35.0 and 2.6 mg/kg, respectively) followed by the chronic administration of 40.0 mg/kg PPA (administered IP, 15 min prior to each session). When responding returned to prechronic rates, the dose-response curves were redetermined for both PPA (ED50 = 220 mg/kg) and amphetamine (ED50 = 4.8 mg/kg). In a second set of rats, trained under similar conditions, it was observed that pretreatment with alpha-methyltyrosine (AMT, 100 mg/kg IP, 2 h presession) antagonized the disruptive effects of both PPA and amphetamine, whereas pretreatment with reserpine (0.31 mg/kg, IP, 12 h presession) antagonized the disruptive effects of PPA, but exacerbated the disruptive effects of amphetamine. In a separate experiment, the repeated administration of PPA 100 mg/kg or 200 mg/kg IP resulted in no long-lasting depletions of rat striatal dopamine, serotonin, or 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations. These observations indicate that PPA and amphetamine share a similar mechanism of action to the degree that cross-tolerance develops, but which is nonetheless dissociable with respect to their differential sensitivity to antagonists and their neurotoxic efficacy.

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

    SciTech Connect

    Foye, W.O. )

    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.

  2. Determination of amphetamine and methamphetamine in umbilical cord using liquid chromatography-tandem mass spectrometry.

    PubMed

    Jones, Joseph; Rios, Rosemarie; Jones, Mary; Lewis, Douglas; Plate, Charles

    2009-11-01

    The use of meconium as a drug-screening matrix for newborns has been the gold standard of care for the past two decades. A recent study using matched pairs of meconium and umbilical cord demonstrated a high degree of agreement. The use of liquid chromatography-tandem mass spectrometry as a means to confirm amphetamines presumptive positive umbilical cord specimens for amphetamine and methamphetamine is described here for the first time. The limit of detection for both compounds was 0.2 ng/g. The limit of quantitation for both compounds was 0.6 ng/g. The assay was linear for both compounds up to 100 ng/g.

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

    SciTech Connect

    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.

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

    PubMed

    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

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

    PubMed Central

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

    2016-01-01

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

  6. 1,3-Dimethyl-5-(3,4,5-tris(alkoxy)benzoyl) barbituric acid derivatives and their liquid crystalline difluoroboron complexes: Synthesis, characterization and comparative investigations of mesomorphic, thermotropic and thermo-morphologic properties

    NASA Astrophysics Data System (ADS)

    Giziroglu, Emrah; Nesrullajev, Arif; Orhan, Nil

    2014-01-01

    A series of 1,3-dimethyl-5-(3,4,5-tris(alkoxy)benzoyl) barbituric acid derivatives 1a-4a with various chain length were synthesized by our group for the first time through the addition of 1,3-dimethyl barbituric acid to 3,4,5-tris(alkoxy)benzoyl chloride at room temperature in presence of pyridine. For preparation of their difluoroboron complexes, the derivatives 1a-4a reacts with borontrifluoride in the presence of triethylamine affording 1b-4b in moderate yields. All derivatives and complexes have been fully characterized by MS, FT-IR and multinuclear NMR spectroscopy. We also explored their liquid crystal properties by using POM, OM, CTW and DSC techniques. The results show that 3b and 4b with longer alkyl chain are monomorphic mesogens and exhibited enantiotropic thermotropic liquid crystalline mesophases. Investigation of their mesomorphic, thermo-morphologic and thermotropic properties is presented in this work.

  7. Imaging human intrasynaptic dopamine release by IV cocaine and amphetamine

    SciTech Connect

    Wong, D.F.; Hong, C.; Yokoi, F.

    1995-05-01

    Intrasynaptic dopamine (DA) release was measured with C-11 Raclopride (RAC) PET in 15 human subjects with two psychostimulant drugs, IV cocaine or IV amphetamine (AMPH). Eleven cocaine users received IV saline then cocaine with high specific activity (SA) tracer RAC by IV bolus. To determine the optimal timing of drug administration, subjects received 48mg cocaine at 0 min.(1 subject), 4 min.(3 subjects) or 10 min.(7 subjects) post injection (mpi). One received 32mg at 4 and 16mg at 10 mpi. In a separate paradigm, the effect of AMPH not only on the binding of Hi SA but also on the receptor density (B{sub max}) using Hi SA and low SA was examined. Four normals received 2 pairs of Hi SA and Low SA RAC PET scans, each pair separated by 1 week to estimate 2 B{sub max}`s, one affected by AMPH. Before the 2nd pair, 0.3mg/kg IV AMPH was given in the times corresponding to the AMPH times for the 1s B{sub max} measurement. All were scanned on a GE 4096WB+PET with 50 frames over 90 min with radial arterial plasma sampling and HPLC metabolite correction. Neuropsychological-endocrine testing was done concurrently. All subjects had a marked psychophysiological response for cocaine or AMPH (less with Low SA RAC). However, evidence of substantial DA release was not consistent with IV cocaine nor correlated with any timing of cocaine vs. RAC, except for an overall trend for RAC reduction with cocaine. The % change in k{sub 3}/k{sub 4} by graphical analysis ranged from +10 to -21%, with similar changes by other methods of quantification, such as k{sub 3}/k{sub 4} constrained to cerebellar K{sub 1}/k{sub 2}, and simple tissue ratios comparisons. IV AMPH showed DA release (19% {plus_minus} 2 (SEM) decrease) in all Hi SA RAC (k{sub 3}/k{sub 4}) by graphical analysis. The calculation of B{sub max} in putamen using Scatchard analysis (baseline B{sub max}29{plus_minus}2) showed 12 to 28% decreases following AMPH.

  8. The enigma of fetal alcohol neurotoxicity.

    PubMed

    Olney, John W; Wozniak, David F; Farber, Nuri B; Jevtovic-Todorovic, Vesna; Bittigau, Petra; Ikonomidou, Chrysanthy

    2002-01-01

    The neurotoxic effects of ethanol on the human fetal brain (fetal alcohol syndrome, FAS) have been recognized for three decades, but the underlying mechanisms have remained elusive. Recently, we discovered that a single episode of ethanol intoxication lasting for several hours can trigger a massive wave of apoptotic neurodegeneration in the developing rat or mouse brain. The window of vulnerability coincides with the developmental period of synaptogenesis, also known as the brain growth-spurt period, which in rodents is a postnatal event, but in humans extends from the sixth month of gestation to several years after birth. We propose that the N-methyl-D-aspartate (NMDA) antagonist and gamma-aminobutyric (GABA)mimetic properties of ethanol are responsible for its apoptogenic action, in that we have found that other drugs that block NMDA glutamate receptors or mimic GABA at GABA(A) receptors also trigger apoptotic neurodegeneration in the developing brain. Our findings have clinical significance, not only because they can explain the reduced brain mass and neurobehavioral disturbances associated with the human FAS, but because many agents in the human environment, other than ethanol, have NMDA antagonist or GABAmimetic properties. Such agents include drugs that may be abused by pregnant mothers [phencyclidine (angel dust), ketamine (Special K), nitrous oxide (laughing gas), barbiturates, benzodiazepines], and many medicinals used in obstetric and pediatric neurology (anticonvulsants), and anesthesiology (all general anesthetics are either NMDA antagonists or GABAmimetics). PMID:12108574

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

    PubMed

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

    2014-08-01

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

  10. The effects of amphetamine, butorphanol, and their combination on cocaine self-administration.

    PubMed

    Smith, Mark A; Pennock, Michael M; Pitts, Elizabeth G; Walker, Katherine L; Lang, Kimberly C

    2014-11-01

    There have been recent calls to examine the efficacy of drug-combination therapies in the treatment of substance use disorders. The purpose of the present study was to examine the ability of a novel stimulant-opioid combination to reduce cocaine self-administration, and to compare these effects to those of each drug administered alone. To this end, male Long-Evans rats were implanted with intravenous catheters and trained to self-administer cocaine under positive reinforcement contingencies. Once self-administration was acquired, rats were divided into four different groups and treated chronically for 20 days with (1) saline, (2) the psychomotor stimulant and monoamine releaser amphetamine, (3) the mu/kappa opioid agonist butorphanol, or (4) a combination of amphetamine and butorphanol. During chronic treatment, cocaine self-administration was examined on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. On the FR schedule, butorphanol significantly decreased cocaine self-administration, but this effect was not enhanced by amphetamine. On the PR schedule, amphetamine and butorphanol non-significantly decreased cocaine self-administration when administered alone but significantly decreased cocaine self-administration when administered in combination. These data suggest that under some conditions (e.g., when the response requirement of cocaine is high), a dual stimulant-opioid pharmacotherapy may be more effective than a single-drug monotherapy. PMID:25127681

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

    PubMed

    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.

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

    PubMed

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

    2016-05-20

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

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

    PubMed

    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.

  14. Increased lever pressing for amphetamine after pimozide in rats: implications for a dopamine theory of reward.

    PubMed

    Yokel, R A; Wise, R A

    1975-02-14

    Low and high doses of a dopamine blocking agent had effects on lever pressing for intravenous amphetamine reward which resembled the effects of reward reduction and reward termination, respectively. Noradrenaline blockade had no such effects. A role in central mediation of reward perception is suggested for dopamine but not for noradrenaline.

  15. Famprofazone as the source of methamphetamine and amphetamine in urine specimen collected during sport competition.

    PubMed

    Tseng, Ying Lung; Lin, Chien-Tzong; Wang, Sheng-Meng; Liu, Ray H

    2007-03-01

    During a sport competition event in Taiwan, one urine specimen was found positive for both methamphetamine (2688 ng/mL) and amphetamine (462 ng/mL). The specimen donor claimed that she had taken Gewolen (a nonprescription drug manufactured in Taiwan) for treating abdominal pain and the medication was presented. Laboratory investigation confirmed that Gewolen contains famprofazone, which is known to metabolize to methamphetamine and amphetamine and is included in the prohibited list of the World Anti-Doping Agency. Study on the excretion profiles of three volunteers ingesting 50 mg famprofazone produced the following patterns similar to that observed in the case specimen: (a) the ratio of methamphetamine to amphetamine was approximately 6 to 1; (b) d- and l-enantiomers of both methamphetamine and amphetamine were present, while the amount of l-methamphetamine was 3-4-fold greater than its counterpart. The data suggested that famprofazone (as the ingredient of Gewolen) was likely the source of the prohibited drugs found in the case specimen.

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed

    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).

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

    PubMed

    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.

  19. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Amphetamine and methamphetamine inhalers regarded as prescription drugs. 250.101 Section 250.101 Food and Drugs FOOD AND DRUG ADMINISTRATION...-enforcement officials, health officials, individual physicians, parents, and others as well as from Food...

  20. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Amphetamine and methamphetamine inhalers regarded as prescription drugs. 250.101 Section 250.101 Food and Drugs FOOD AND DRUG ADMINISTRATION...-enforcement officials, health officials, individual physicians, parents, and others as well as from Food...

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

    ERIC Educational Resources Information Center

    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…

  2. Enantiomer profiling of high loads of amphetamine and MDMA in communal sewage: a Dutch perspective.

    PubMed

    Emke, Erik; Evans, Sian; Kasprzyk-Hordern, Barbara; de Voogt, Pim

    2014-07-15

    Analysis of wastewater with an aim of community-wide estimation of drug use is a new and very promising approach. Until now it was very difficult to determine if mass loads of studied drugs were actually originating from consumption, or disposal of unused drugs or production waste. This uncertainty in the estimation of community wide drugs use should not be underestimated. This paper aims to apply for the first time enantiomeric profiling in verifying sources of the presence of MDMA and amphetamine in wastewater based on a case study in two Dutch cities: Utrecht and Eindhoven. The results showed that MDMA is usually present in wastewater due to its consumption (MDMA enriched with R(-)-enantiomer). Excessively high mass loads of MDMA during a sampling campaign in Utrecht in 2011 proved to be racemic indicating direct disposal of unused MDMA possibly as a result of a police raid at a nearby illegal production facility. Enantiomeric profiling was also undertaken in order to verify the origin of unexpectedly high mass loads of amphetamine in the city of Eindhoven in 2011. Unfortunately, a distinction between consumption and direct disposal of unused amphetamine in Dutch wastewater could not be achieved. Further work will have to be undertaken to fully understand sources of amphetamine in Dutch wastewaters.

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

    SciTech Connect

    Cody, J.T. )

    1990-01-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  6. The effects of amphetamine, butorphanol, and their combination on cocaine self-administration.

    PubMed

    Smith, Mark A; Pennock, Michael M; Pitts, Elizabeth G; Walker, Katherine L; Lang, Kimberly C

    2014-11-01

    There have been recent calls to examine the efficacy of drug-combination therapies in the treatment of substance use disorders. The purpose of the present study was to examine the ability of a novel stimulant-opioid combination to reduce cocaine self-administration, and to compare these effects to those of each drug administered alone. To this end, male Long-Evans rats were implanted with intravenous catheters and trained to self-administer cocaine under positive reinforcement contingencies. Once self-administration was acquired, rats were divided into four different groups and treated chronically for 20 days with (1) saline, (2) the psychomotor stimulant and monoamine releaser amphetamine, (3) the mu/kappa opioid agonist butorphanol, or (4) a combination of amphetamine and butorphanol. During chronic treatment, cocaine self-administration was examined on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. On the FR schedule, butorphanol significantly decreased cocaine self-administration, but this effect was not enhanced by amphetamine. On the PR schedule, amphetamine and butorphanol non-significantly decreased cocaine self-administration when administered alone but significantly decreased cocaine self-administration when administered in combination. These data suggest that under some conditions (e.g., when the response requirement of cocaine is high), a dual stimulant-opioid pharmacotherapy may be more effective than a single-drug monotherapy.

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

    PubMed Central

    Sadeghi, Hasan; Ebrahimi, Leyla; Vatandoust, Leyla

    2015-01-01

    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. PMID:26870707

  8. Adrenaline Instead of Amphetamine-Replacing Psychoactive Substances with Parachute Jumps.

    PubMed

    Makarowski, Ryszard; Makarowski, Piotr; Kamiński, Zbigniew

    2016-01-01

    The "Adrenaline Instead of Amphetamine" program was launched by Gdańsk's MONAR association-a center for drug treatment. The purpose of the program was to show some alternatives to using psychoactive substances and to propose replacing these anti-medical behaviors with parachuting. The treatment effectiveness in this center is about 30%, and the program's effectiveness was 80%. PMID:27649360

  9. Adrenaline Instead of Amphetamine-Replacing Psychoactive Substances with Parachute Jumps.

    PubMed

    Makarowski, Ryszard; Makarowski, Piotr; Kamiński, Zbigniew

    2016-01-01

    The "Adrenaline Instead of Amphetamine" program was launched by Gdańsk's MONAR association-a center for drug treatment. The purpose of the program was to show some alternatives to using psychoactive substances and to propose replacing these anti-medical behaviors with parachuting. The treatment effectiveness in this center is about 30%, and the program's effectiveness was 80%.

  10. The Effects of Amphetamine, Butorphanol, and Their Combination on Cocaine Self-Administration

    PubMed Central

    Smith, Mark A.; Pennock, Michael M.; Pitts, Elizabeth G.; Walker, Katherine L.; Lang, Kimberly C.

    2014-01-01

    There have been recent calls to examine the efficacy of drug-combination therapies in the treatment of substance use disorders. The purpose of the present study was to examine the ability of a novel stimulant-opioid combination to reduce cocaine self-administration, and to compare these effects to those of each drug administered alone. To this end, male Long-Evans rats were implanted with intravenous catheters and trained to self-administer cocaine under positive reinforcement contingencies. Once self-administration was acquired, rats were divided into four different groups and treated chronically for 20 days with (1) saline, (2) the psychomotor stimulant and monoamine releaser amphetamine, (3) the mu/kappa opioid agonist butorphanol, or (4) a combination of amphetamine and butorphanol. During chronic treatment, cocaine self-administration was examined on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. On the FR schedule, butorphanol significantly decreased cocaine self-administration, but this effect was not enhanced by amphetamine. On the PR schedule, amphetamine and butorphanol non-significantly decreased cocaine self-administration when administered alone but significantly decreased cocaine self-administration when administered in combination. These data suggest that under some conditions (e.g., when the response requirement of cocaine is high), a dual stimulant-opioid pharmacotherapy may be more effective than a single-drug monotherapy. PMID:25127681

  11. Amphetamine affects the start of responding in the peak interval timing task.

    PubMed

    Taylor, Kathleen M; Horvitz, Jon C; Balsam, Peter D

    2007-02-22

    In this paper we investigate how amphetamine affects performance in a PI task by comparing two analyses of responding during peak trials. After training on 24 s fixed interval (FI-24) with 96 s peak trials, rats were given amphetamine for 4 consecutive days at doses of .5 and 1.0 mg/kg. Responses during peak trials were fitted with a Gaussian distribution to estimate the expected time of reinforcement from the peak time. A single trials analysis was also performed to determine the start time and stop time of the transition into and out of a high rate of responding on each peak trial. Amphetamine significantly decreased peak times as measured with the Gaussian curve fitting. However, in the single trials analysis, animals initiated responding significantly earlier, but did not stop responding earlier. Thus, fitting a Gaussian to the average performance across trials sometimes provides a different characterization of the timing process than does analyzing the start and stop of responding on individual trials. In the current experiment, the latter approach provided a more precise characterization of the effects of amphetamine on response timing.

  12. [Pathomorphological features of chronic toxic osteomyelitis in drug addicts taking amphetamine of a street drugs brand].

    PubMed

    Ruzin, G P; Tkachenko, O V; Miroshnichenko, M S; Pliten', O N

    2013-06-01

    In the article the authors present the pathological features of chronic toxic osteomyelitis in drug addicts taking amphetamine of handicraft production (pervitin, vint). It is shown that this pathology is characterized by the predominance of marked degenerative, necrotic and inflammatory changes over the reparative processes.

  13. Alcohol during Pregnancy

    MedlinePlus

    ... Home > Pregnancy > Is it safe? > Alcohol during pregnancy Alcohol during pregnancy E-mail to a friend Please ... and fetal alcohol spectrum disorders. How does drinking alcohol during pregnancy affect your baby's health? Drinking alcohol ...

  14. Alcohol Energy Drinks

    MedlinePlus

    ... Home / About Addiction / Alcohol / Alcohol Energy Drinks Alcohol Energy Drinks Read 17728 times font size decrease font size increase font size Print Email Alcohol energy drinks (AEDs) or Caffeinated alcoholic beverages (CABs) are ...

  15. The influence of ionotropic and metabotropic glutamate receptor ligands on anxiety-like effect of amphetamine withdrawal in rats.

    PubMed

    Koltunowska, D; Gibula-Bruzda, E; Kotlinska, J H

    2013-08-01

    Chronic amphetamine use results in anxiety-like states after drug cessation. The aim of the study was to determine a role of ionotropic and metabotropic glutamate receptor ligands in amphetamine-evoked withdrawal anxiety in the elevated plus-maze test in rats. In our study memantine (8 and 12 mg/kg), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist did not reduce amphetamine withdrawal anxiety. Acamprosate (NMDA and metabotropic glutamate 5 receptor (mGluR5) antagonist) at the dose 200 and 400mg/kg showed anxiolytic-like effect, thus increasing the percent of time spent in open arms and a number of open arm entries. mGluR5 selective antagonist, MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine hydrochloride) and mGluR2/3 agonist, LY354740 (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid), caused effects similar to acamprosate at doses 1.25-5mg/kg and 2.5-5mg/kg, respectively. None of the glutamate ligands influenced locomotor activity of rats when given to the saline-treated group. Taking into account the positive correlation between amphetamine withdrawal-induced anxiety and relapse to amphetamine taking, our results suggest that modulation of mGluRs may prevent relapse to amphetamine and might pose a new direction in amphetamine abuse therapy. PMID:23623810

  16. Involvement of hypothalamic PI3K–STAT3 signalling in regulating appetite suppression mediated by amphetamine

    PubMed Central

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

    2014-01-01

    BACKGROUND AND PURPOSE Appetite suppression induced by amphetamine has been attributed to its inhibition of neuropeptide Y (NPY) neurons and activation of pro-opiomelanocortin (POMC) neurons in the hypothalamus. This study examined whether STAT3 was involved in these actions of amphetamine. EXPERIMENTAL APPROACH Rats were given amphetamine daily for 4 days. Changes in the expression of NPY, POMC, melanocortin MC3 receptors, PI3K and STAT3 in the hypothalamus were assessed by RT-PCR and Western blotting. Antisense oligonucleotides to STAT3 were also used. KEY RESULTS Expression of NPY decreased with a maximum effect day 2 of amphetamine treatment. Expression of POMC, MC3 receptors, PI3K and STAT3 increased with a maximum response on day 2. Moreover, phosphorylation of STAT3 and its DNA binding activity increased and was expressed in a similar pattern. Infusion (i.c.v.) of STAT3 antisense at 60 min before amphetamine treatment, partly blocked amphetamine-induced anorexia and modulated expression of NPY, POMC, MC3 receptors and PI3K, indicating the involvement of STAT3 in amphetamine-treated rats. CONCLUSIONS AND IMPLICATIONS Hypothalamic PI3K–STAT3 signalling participated in the regulation of NPY- and POMC-mediated appetite suppression. These findings may contribute to a better understanding of anorectic drugs. PMID:24597972

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

    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 1.0 Gy 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. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    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.

  19. The Reliability and Validity of Drug Users' Self Reports of Amphetamine Use Among Primarily Heroin and Cocaine Users

    PubMed Central

    Napper, Lucy E.; Fisher, Dennis G.; Johnson, Mark E.; Wood, Michele M.

    2009-01-01

    Relatively few studies have addressed the psychometric properties of self-report measures of amphetamine use. This study examines the reliability and validity of the Risk Behavior Assessment's (RBA) lifetime and recent amphetamine-use questions. To evaluate validity, 4027 out-of-treatment primarily cocaine and heroin users provided urine samples that were compared to self-report data; to evaluate reliability, 218 completed the RBA at two time points, 48 hours apart. In the overall sample, self-reports demonstrated moderately high validity, with a 95% accuracy rate (kappa =.54). When analysis was restricted to recent amphetamine users validity was slightly lower (71.5% accuracy; kappa = .41). Test-retest data indicated good reliability for self-reports of ever having used amphetamine (kappa =.79), and amphetamine use in the past 30 days (.75 < r < .91). Out-of-treatment drug users provided accurate self-reports of amphetamine use. Reliable and valid measures are essential for describing and predicting trends in amphetamine use, evaluating the effectiveness of interventions, and developing policies and programs. PMID:20053503

  20. A new synthetic methodology for the preparation of biocompatible and organo-soluble barbituric- and thiobarbituric acid based chitosan derivatives for biomedical applications.

    PubMed

    Shahzad, Sohail; Shahzadi, Lubna; Mahmood, Nasir; Siddiqi, Saadat Anwar; Rauf, Abdul; Manzoor, Faisal; Chaudhry, Aqif Anwar; Rehman, Ihtesham Ur; Yar, Muhammad

    2016-09-01

    Chitosan's poor solubility especially in organic solvents limits its use with other organo-soluble polymers; however such combinations are highly required to tailor their properties for specific biomedical applications. This paper describes the development of a new synthetic methodology for the synthesis of organo-soluble chitosan derivatives. These derivatives were synthesized from chitosan (CS), triethyl orthoformate and barbituric or thiobarbituric acid in the presence of 2-butannol. The chemical interactions and new functional motifs in the synthesized CS derivatives were evaluated by FTIR, DSC/TGA, UV/VIS, XRD and (1)H NMR spectroscopy. A cytotoxicity investigation for these materials was performed by cell culture method using VERO cell line and all the synthesized derivatives were found to be non-toxic. The solubility analysis showed that these derivatives were readily soluble in organic solvents including DMSO and DMF. Their potential to use with organo-soluble commercially available polymers was exploited by electrospinning; the synthesized derivatives in combination with polycaprolactone delivered nanofibrous membranes.

  1. Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P-450 monooxygenase induced by barbiturates in Bacillus megaterium.

    PubMed

    Narhi, L O; Fulco, A J

    1986-06-01

    A unique cytochrome P-450-dependent fatty acid monooxygenase from Bacillus megaterium ATCC 14581 is strongly induced by phenobarbital (Narhi, L. O., and Fulco, A. J. (1982) J. Biol. Chem. 257, 2147-2150) and many other barbiturates (Kim, B.-H., and Fulco, A. J. (1983) Biochem. Biophys. Res. Commun. 116, 843-850). This monooxygenase has now been purified to homogeneity from pentobarbital-induced bacteria as a single polypeptide with a molecular weight of 119,000 +/- 5,000 daltons. In the presence of NADPH and O2, it can catalyze the oxygenation of long chain fatty acids without the aid of any other protein. The enzyme has a catalytic center activity of 4,600 nmol of fatty acid oxygenated per nmol of P-450 (the highest activity yet reported for a P-450-dependent monooxygenase) and also functions as a highly active cytochrome c reductase in the presence of NADPH. The purified holoenzyme is a soluble protein containing 40 mol % hydrophobic amino acid residues and 1 mol each of FAD and FMN/mol of heme. It is isolated and purified in the low spin form but is converted to the high spin form in the presence of long chain fatty acids. The enzyme, which catalyzes the omega-2 hydroxylation of saturated fatty acids and the hydroxylation and epoxidation of unsaturated fatty acids has its highest affinity (Km = 2 +/- 1 microM) for the C15 and C16 chain lengths. PMID:3086309

  2. Stability of [123I]IBZM SPECT measurement of amphetamine-induced striatal dopamine release in humans.

    PubMed

    Kegeles, L S; Zea-Ponce, Y; Abi-Dargham, A; Rodenhiser, J; Wang, T; Weiss, R; Van Heertum, R L; Mann, J J; Laruelle, M

    1999-03-15

    Binding competition between endogenous dopamine (DA) and the D2 receptor radiotracer [123I]IBZM allows measurement of the change in synaptic DA following amphetamine challenge with SPECT in the living human brain. Previous investigations using this technique in healthy subjects have shown that the magnitude of amphetamine effect on [123I]IBZM binding potential (BP) is small (range between 5 to 15% decrease), and that a large between-subject variability in this effect is observed. Therefore, it was unclear how much of the apparent between-subject variability was due to a low signal-to-noise ratio in the measurement, vs. true between-subject differences in the magnitude of the response. The goals of this investigation were to test the within-subject reproducibility and reliability of amphetamine-induced decrease in [123I]IBZM BP with a test/retest paradigm, and to establish the presence or absence of tolerance or sensitization to single administration ofi.v. amphetamine. Six healthy male subjects, never previously exposed to psychostimulants, twice underwent measurement of striatal amphetamine-induced DA release (between-measurement interval 16 +/- 10 days) using SPECT and the [123I]IBZM constant infusion technique. Results demonstrated an excellent within-subject reproducibility of amphetamine-induced DA release: amphetamine-induced decreases in [123I]IBZM BP were significant on each day, and had an intraclass correlation coefficient (ICC) of 0.89. Moreover, values from the second experiment were not significantly different from first experiment, suggesting the absence of either sensitization or tolerance to the effect of amphetamine on DA release in these experimental conditions. The subjective activation, as rated by the subjects on analog scales, was also highly reproducible. In conclusion, this scanning technique provides a reliable measurement of amphetamine-induced reduction of [123I]IBZM BP and enables detection of between-subject differences that appear

  3. Alcohol conversion

    DOEpatents

    Wachs, Israel E.; Cai, Yeping

    2002-01-01

    Preparing an aldehyde from an alcohol by contacting the alcohol in the presence of oxygen with a catalyst prepared by contacting an intimate mixture containing metal oxide support particles and particles of a catalytically active metal oxide from Groups VA, VIA, or VIIA, with a gaseous stream containing an alcohol to cause metal oxide from the discrete catalytically active metal oxide particles to migrate to the metal oxide support particles and to form a monolayer of catalytically active metal oxide on said metal oxide support particles.

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

    PubMed

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

    2016-08-15

    The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine>methamphetamine>hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation

  5. Acute methoxetamine and amphetamine poisoning with fatal outcome: a case report.

    PubMed

    Wiergowski, Marek; Anand, Jacek Sein; Krzyżanowski, Maciej; Jankowski, Zbigniew

    2014-08-01

    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.

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

    PubMed

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

    2015-12-18

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

  7. Pharmacological modulation of amphetamine-induced dyskinesia in transplanted hemi-parkinsonian rats.

    PubMed

    Smith, Gaynor A; Breger, Ludivine S; Lane, Emma L; Dunnett, Stephen B

    2012-10-01

    Foetal cell transplantation in patients with Parkinson's disease can induce motor complications independent of L-DOPA administration, known as graft-induced dyskinesia. In the 6-OHDA lesioned rat model of Parkinson's disease, post-transplantation abnormal movements can develop in response to an amphetamine challenge, a behaviour which is used to model graft-induced dyskinesia. Although L-DOPA-induced dyskinesia has been well characterised pharmacologically, we lack knowledge on the modulation of post-transplantation amphetamine-induced dyskinesia which may shed light on the mechanisms underlying graft-induced dyskinesia. We assessed a series of drugs effective at reducing L-DOPA-induced dyskinesia against post-transplantation amphetamine-induced dyskinesia. Agents include: dopaminergic antagonists (D₁: CP94253; D₂: SCH-22390; D₃: nafadotride), serotonergic agonists (5-HT(1A): 8-OH-DPAT; 5-HT(1B): CP94253), opioid antagonist (μ: naloxone), cannabinoid agonist (CB₁: WIN55, 212-2), adrenergic antagonist (α₁ and α₂: yohimbine) and glutamatergic antagonists (NMDA: amantadine and MK-801; mGluR5: MTEP; AMPA: IEM1460). Abnormal involuntary movements in response to amphetamine were decreased by SCH-22390, raclopride, CP94253 and 8-OH-DPAT, yet were unaltered by naloxone, WIN55, 212-2, yohimbine, amantadine, MTEP and IEM1460. Unusually, MK-801 increased the appearance of amphetamine-induced dyskinesia. The results suggest that dopaminergic, serotoninergic and glutamatergic systems are likely to have a fundamental role in the development of graft-induced dyskinesias, which are mechanistically distinct from L-DOPA-induced behvaviours. Importantly, the expression of D₁ and D₂ receptors was unrelated to the severity of AIMs.

  8. Medial prefrontal cortex inactivation attenuates the diurnal rhythm in amphetamine reward.

    PubMed

    Baltazar, R M; Coolen, L M; Webb, I C

    2014-01-31

    Psychostimulant reward, as assessed via the conditioned place preference (CPP) paradigm, exhibits a daily rhythm with peaks in the late dark and early light periods, and a nadir near the light-to-dark transition. While this diurnal rhythm is correlated with neural activity in several corticolimbic structures, the brain regions mediating this behavioral rhythm remain unknown. Here, we examine the role of the ventral medial prefrontal cortex (mPFC). The effects of excitotoxic mPFC lesions on daily rhythms in amphetamine CPP were examined at previously observed peak (zeitgeber time [ZT] 23) and nadir times (ZT11). mPFC lesions encompassing the prelimbic and infralimbic subregions increased the CPP for amphetamine at the nadir time, thereby eliminating the daily rhythm in amphetamine reward. To examine the effects of transient mPFC inactivation, rats received intra-mPFC infusions of GABA receptor agonists during the acquisition or expression phases of CPP testing. Inactivation of the ventral mPFC at either of these phases also eliminated the daily rhythm in amphetamine-induced CPP via an increase in drug-paired chamber dwell time at the baseline nadir. Together, these results indicate that the ventral mPFC plays a critical role in mediating the diurnal rhythm in amphetamine CPP during both the acquisition and expression of learned reward-context associations. Moreover, as the loss of rhythmicity occurs via an increase at the nadir point, these results suggest that excitatory output from the ventral mPFC normally inhibits context-elicited reward seeking prior to the light-to-dark transition.

  9. Acute methoxetamine and amphetamine poisoning with fatal outcome: a case report.

    PubMed

    Wiergowski, Marek; Anand, Jacek Sein; Krzyżanowski, Maciej; Jankowski, Zbigniew

    2014-08-01

    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. PMID:25060403

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

    PubMed Central

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

    2006-01-01

    AIM: To study the effects of amphetamine, an indirect-acting adrenomimetic compound on the indomethacin-induced 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, 25 and 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 indomethacin-induced gastric ulcerations in rats. It is suggested that the adrenergic system is involved in the gastric mucosa protection. PMID:17131481

  11. Alcoholic ketoacidosis

    MedlinePlus

    Tests may include: Arterial blood gases (measure the acid/base balance and oxygen level in blood) Blood alcohol ... PA: Elsevier Saunders; 2013:chap 161. Seifter JL. Acid-Base disorders. In: Goldman L, Schafer AI, eds. Goldman's ...

  12. Alcohol withdrawal

    MedlinePlus

    ... Seeing or feeling things that aren't there (hallucinations) Seizures Severe confusion ... alcohol withdrawal. You will be watched closely for hallucinations and other signs of delirium tremens. Treatment may ...

  13. Affinity isolation and characterization of cytochrome P450 102 (BM-3) from barbiturate-induced Bacillus megaterium.

    PubMed

    Black, S D; Linger, M H; Freck, L C; Kazemi, S; Galbraith, J A

    1994-04-01

    Cytochrome P450 102 (BM-3) is a catalytically self-sufficient enzyme from Bacillus megaterium that is presently accepted as an important model of the mammalian microsomal P450 monooxygenase system. We have developed a novel affinity approach to purify P450 102 in a single chromatographic step and have studied the spectroscopic, catalytic, nucleotide binding, and crystallization properties of the highly purified enzyme. B. megaterium ATCC 14581 was grown to high cell density, and P450 102 was purified rapidly and in high yield by chromatography on adenosine-2',5'-diphosphate agarose from crude cell-free extract. The cytochrome bound to the column with remarkable avidity, in contrast to the significantly weaker binding observed for NADPH-cytochrome P450 reductase. Chromatographic behavior also showed that the cytochrome bound NADP(+)-type nucleotides more tightly than any other cellular polypeptide. The purified protein was electrophoretically homogeneous and had essentially theoretical contents of FAD, FMN, and heme. Optical spectra showed the expected heme and flavin absorption bands, and three previously undescribed charge-transfer-type absorptions were characterized. Molar extinction coefficients in the oxidized, fully reduced, and ferrous carbonyl states have been determined; notable is the large soret extinction in the ferrous carbonyl state (epsilon 449 nm = 143,500 M-1 cm-1). Final preparations were active in the oxidation of a wide variety of substrates. Of the C14 alkyl compounds studied, tetradecyltrimethylammonium bromide showed the highest substrate-dependent oxidation of NADPH, followed by myristate and myristyl alcohol; however, myristate exhibited the lowest Km value. Activities were tightly coupled to NADPH oxidation (> 97%). Phenobarbital, benzphetamine, cocaine, cyclohexane, methanol, ethanol, retinoic acid, benzoate, heptaflourobutyrate, and 7-ethoxycoumarin were not substrates. NADP+ titrations showed, as expected, that the coenzyme was bound

  14. One barbiturate and two solvated thiobarbiturates containing the triply hydrogen-bonded ADA/DAD synthon, plus one ansolvate and three solvates of their coformer 2,4-diaminopyrimidine.

    PubMed

    Hützler, Wilhelm Maximilian; Egert, Ernst; Bolte, Michael

    2016-09-01

    A path to new synthons for application in crystal engineering is the replacement of a strong hydrogen-bond acceptor, like a C=O group, with a weaker acceptor, like a C=S group, in doubly or triply hydrogen-bonded synthons. For instance, if the C=O group at the 2-position of barbituric acid is changed into a C=S group, 2-thiobarbituric acid is obtained. Each of the compounds comprises two ADA hydrogen-bonding sites (D = donor and A = acceptor). We report the results of cocrystallization experiments of barbituric acid and 2-thiobarbituric acid, respectively, with 2,4-diaminopyrimidine, which contains a complementary DAD hydrogen-bonding site and is therefore capable of forming an ADA/DAD synthon with barbituric acid and 2-thiobarbituric acid. In addition, pure 2,4-diaminopyrimidine was crystallized in order to study its preferred hydrogen-bonding motifs. The experiments yielded one ansolvate of 2,4-diaminopyrimidine (pyrimidine-2,4-diamine, DAPY), C4H6N4, (I), three solvates of DAPY, namely 2,4-diaminopyrimidine-1,4-dioxane (2/1), 2C4H6N4·C4H8O2, (II), 2,4-diaminopyrimidine-N,N-dimethylacetamide (1/1), C4H6N4·C4H9NO, (III), and 2,4-diaminopyrimidine-1-methylpyrrolidin-2-one (1/1), C4H6N4·C5H9NO, (IV), one salt of barbituric acid, viz. 2,4-diaminopyrimidinium barbiturate (barbiturate is 2,4,6-trioxopyrimidin-5-ide), C4H7N4(+)·C4H3N2O3(-), (V), and two solvated salts of 2-thiobarbituric acid, viz. 2,4-diaminopyrimidinium 2-thiobarbiturate-N,N-dimethylformamide (1/2) (2-thiobarbiturate is 4,6-dioxo-2-sulfanylidenepyrimidin-5-ide), C4H7N4(+)·C4H3N2O2S(-)·2C3H7NO, (VI), and 2,4-diaminopyrimidinium 2-thiobarbiturate-N,N-dimethylacetamide (1/2), C4H7N4(+)·C4H3N2O2S(-)·2C4H9NO, (VII). The ADA/DAD synthon was succesfully formed in the salt of barbituric acid, i.e. (V), as well as in the salts of 2-thiobarbituric acid, i.e. (VI) and (VII). In the crystal structures of 2,4-diaminopyrimidine, i.e. (I)-(IV), R2(2)(8) N-H...N hydrogen-bond motifs are preferred and, in two

  15. [Development of tolerance to the activating action of morphine, fenamin, and alcohol on the positive reinforcement system of rats].

    PubMed

    Burov, Iu V; Borisenko, S A

    1980-06-01

    The development of cross tolerance to morphine, amphetamine and alcohol according to their activating effect on the system of positive reinforcement of the brain was shown on the basis of experimental self-stimulation reaction. It is assumed that the common neurophysiological and neurochemical mechanisms, particularly the adrenergic mechanisms of the system of positive reinforcement, lie at the basis of the development of tolerance to the drugs with euphoric type of action.

  16. The administration of atomoxetine during alcohol deprivation induces a time-limited increase in alcohol consumption after relapse.

    PubMed

    Alén, Francisco; Serrano, Antonia; Gorriti, Miguel Ángel; Pavón, Francisco Javier; Orio, Laura; de Heras, Raquel Gómez; Ramírez-López, María Teresa; Antón, María; Pozo, Miguel Ángel; Rodríguez de Fonseca, Fernando

    2014-11-01

    The administration of selective serotonin reuptake inhibitors (SSRIs) typically used as antidepressants increases alcohol consumption after an alcohol deprivation period in rats. However, the appearance of this effect after the treatment with selective noradrenaline reuptake inhibitors (SNRIs) has not been studied. In the present work we examined the effects of a 15-d treatment with the SNRI atomoxetine (1, 3 and 10 mg/kg, i.p.) in male rats trained to drink alcohol solutions in a 4-bottle choice test. The treatment with atomoxetine (10 mg/kg, i.p.) during an alcohol deprivation period increased alcohol consumption after relapse. This effect only lasted one week, disappearing thereafter. Treatment with atomoxetine did not cause a behavioral sensitized response to a challenge dose of amphetamine (1.5 mg/kg, i.p.), indicating the absence of a supersensitive dopaminergic transmission. This effect is markedly different from that of SSRI antidepressants that produced both long-lasting increases in alcohol consumption and behavioral sensitization. Clinical implications are discussed. PMID:25025529

  17. Previous Exposure to Δ9-Tetrahydrocannibinol Enhances Locomotor Responding to but Not Self-Administration of AmphetamineS⃞

    PubMed Central

    Cortright, James J.; Lorrain, Daniel S.; Beeler, Jeff A.; Tang, Wei-Jen

    2011-01-01

    Previous exposure to amphetamine leads to enhanced locomotor and nucleus accumbens (NAcc) dopamine (DA) responding to the drug as well as enhanced amphetamine self-administration. Here, we investigated the effects of exposure to Δ9-tetrahydrocannibinol (Δ9-THC) on behavioral and biochemical responding to amphetamine. Rats in different groups received five exposure injections of vehicle or one of five doses of Δ9-THC (0.4, 0.75, 1.5, 3.0, and 6.0 mg/kg i.p.) and were tested 2 days and 2 weeks later. Exposure to all but the lowest and highest doses of Δ9-THC enhanced the locomotor response to amphetamine (0.75 mg/kg i.p.), but all failed to enhance NAcc DA overflow in response to the drug. Moreover, exposure to 3.0 mg/kg i.p. Δ9-THC increased forskolin-evoked adenylyl cyclase activity in the NAcc and rats' locomotor response to the direct DA receptor agonist apomorphine (1.0 mg/kg s.c.), suggesting that Δ9-THC sensitized locomotor responding to amphetamine by up-regulating postsynaptic DA receptor signaling in the NAcc. Finally, amphetamine self-administration (200 μg/kg/infusion i.v.) was enhanced in amphetamine (5 × 1.5 mg/kg i.p.)-exposed rats, but not in rats exposed to Δ9-THC (5 × 3.0 mg/kg i.p.). Previous exposure to this dose of Δ9-THC modestly increased apomorphine SA (0.5 mg/kg/infusion i.v.). Thus, unlike amphetamine exposure, exposure to Δ9-THC does not enhance the subsequent NAcc DA response to amphetamine or promote amphetamine self-administration. Although Δ9-THC leads to alterations in postsynaptic DA receptor signaling in the NAcc and these can affect the generation of locomotion, these neuroadaptations do not seem to be linked to the expression of enhanced amphetamine self-administration. PMID:21389094

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

    PubMed

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

    2016-05-27

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

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

    PubMed

    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.

  20. Deciding to quit drinking alcohol

    MedlinePlus

    ... Alcohol abuse - quitting drinking; Quitting drinking; Quitting alcohol; Alcoholism - deciding to quit ... pubmed/23698791 . National Institute on Alcohol Abuse and Alcoholism. Alcohol and health. www.niaaa.nih.gov/alcohol- ...

  1. [Value of early acoustic and somatosensory evoked potentials in monitoring and prognostic assessment of coma in barbiturate therapy--comparison with clinical aspects and EEG].

    PubMed

    Reisecker, F; Witzmann, A; Löffler, W; Leblhuber, F; Deisenhammer, E; Valencak, E

    1987-03-01

    25 comatose patients suffering from severe cerebral lesions of different etiology were examined during barbiturate-therapy by Glasgow-Pittsburg-Coma-Scoring-System (GPCS), EEG, somatosensory and brainstem acoustic evoked potentials. The findings were correlated in view of prognostic prediction and importance for monitoring. A modified form of the Glasgow-Outcome-Score (GOS; independent-survival, dependent-survival, dead) was used for evaluating the outcome. In case of an initial GPCS less than 10 points none of the patients survived, in case of GPCS greater than 10 points 11 out of 19 patients survived. The latter relation of survival was also found in patients with improving or impairing scores during the observation period. In case of initial burst-suppression pattern in the EEG 7 out of 11 patients survived, in case of diffuse abnormalities with or with-out additional focal signs - 4 out of 10 patients survived, but in the latter there was none with an outcome of independent survival. All patients with an isoelectric EEG died. In case of bilateral recording of scalp- SEP 7 out of 11 patients survived, in case of unilateral loss of scalp-EP 4 out of 8 patients survived, but in the latter cases none with an outcome of independence. All patients with initial bilateral failure of scalp-SSEP or loss during the observation period died. In case of bilateral registrable BAEP (wave I to V) 11 out of 17 patients survived. All patients with initial uni- or bilateral failure of those potentials or loss during the observation period died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3106004

  2. Cocaine and Amphetamine Induce Overlapping but Distinct Patterns of AMPAR Plasticity in Nucleus Accumbens Medium Spiny Neurons.

    PubMed

    Jedynak, Jakub; Hearing, Matthew; Ingebretson, Anna; Ebner, Stephanie R; Kelly, Matthew; Fischer, Rachel A; Kourrich, Saïd; Thomas, Mark J

    2016-01-01

    Repeated exposure to psychostimulant drugs such as cocaine or amphetamine can promote drug-seeking and -taking behavior. In rodent addiction models, persistent changes in excitatory glutamatergic neurotransmission in the nucleus accumbens (NAc) appear to drive this drug-induced behavioral plasticity. To study whether changes in glutamatergic signaling are shared between or exclusive to specific psychostimulant drugs, we examined synaptic transmission from mice following repeated amphetamine or cocaine administration. Synaptic transmission mediated by AMPA-type glutamate receptors was potentiated in the NAc shell 10-14 days following repeated amphetamine or cocaine treatment. This synaptic enhancement was depotentiated by re-exposure to amphetamine or cocaine. By contrast, in the NAc core only repeated cocaine exposure enhanced synaptic transmission, which was subsequently depotentiated by an additional cocaine but not amphetamine injection during drug abstinence. To better understand the drug-induced depotentiation, we replicated these in vivo findings using an ex vivo model termed 'challenge in the bath,' and showed that drug-induced decreases in synaptic strength occur rapidly (within 30 min) and require activation of metabotropic glutamate receptor 5 (mGluR5) and protein synthesis in the NAc shell, but not NAc core. Overall, these data demonstrate the specificity of neuronal circuit changes induced by amphetamine, introduce a novel method for studying drug challenge-induced plasticity, and define NAc shell medium spiny neurons as a primary site of persistent AMPA-type glutamate receptor plasticity by two widely used psychostimulant drugs.

  3. Rapid and simple method for direct determination of several amphetamines in seized tablets by GC--FID.

    PubMed

    Mitrevski, Blagoj; Zdravkovski, Zoran

    2005-09-10

    A simple and rapid method for direct simultaneous determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA) and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in seized tablets was developed using gas chromatography with flame ionization detection. Separation of all six underivatized amphetamines, including diphenylamine as internal standard, was performed in about 6 min, using SPB-50 capillary column. Amphetamine and methamphetamine eluted with negligible tailing while the other amphetamines had highly symmetrical peaks. Sensitivity per component on-column was in the nanogram range, and reproducibility from 2.6 to 6.6% at low concentration (2.4 microg/mL) and from 1.2 to 2.6% at high (70 microg/mL) concentration. The method has a wide linear range, from Limit of detection (LOD) to almost 200 microg/mL, thus allowing analysis of different samples across a wide range of possible concentrations of amphetamines. This simple, fast and precise method using gas chromatography--flame ionization detector (GC--FID), in conjunction with other methods (TLC, IR, HPLC), can be used for identification of amphetamines and direct determination in seized tablets, especially in laboratories with heavy workload. PMID:15978345

  4. Reinstatement of extinguished amphetamine self-administration by 3,4-methylenedioxymethamphetamine (MDMA) and its enantiomers in rhesus monkeys

    PubMed Central

    McClung, Jessica; Fantegrossi, William

    2010-01-01

    Rationale The effectiveness of MDMA and its enantiomers to reinstate responding previously maintained by drug self-administration has not been thoroughly investigated. Objectives The present study was designed to compare the reinstatement effects of amphetamine, the piperazine-analog BZP, SR(+/−)-MDMA, S(+)-MDMA, R(−)-MDMA, and fenfluramine on behavior maintained under a second-order schedule of intravenous amphetamine self-administration in rhesus monkeys (n=4). Methods Following saline substitution and extinction, a range of doses of amphetamine, BZP, SR(+/−)-MDMA, S(+)-MDMA, R(−)-MDMA, and fenfluramine were administered i.v. as non-contingent priming injections in order to characterize their effectiveness to reinstate responding previously maintained by amphetamine self-administration. Results Priming injections of amphetamine, BZP, SR(+/−)-MDMA, and S(+)-MDMA induced significant reinstatement effects. In contrast, neither R(−)-MDMA nor fenfluramine effectively reinstated behavior. Pretreatment with the selective serotonin transporter inhibitor, fluoxetine, attenuated the reinstatement effects of SR(+/−)-MDMA, S(+)-MDMA, and BZP but had no significant effect on amphetamine-primed reinstatement. Conclusions Given the profile of neurochemical effects published previously, these findings suggest that the reinstatement effects of MDMA are mediated primarily by dopamine release; however, the attenuation of MDMA-induced reinstatement by fluoxetine supports previous research demonstrating the complex behavioral pharmacology of MDMA-like drugs and that the reinstatement effects of MDMA are at least partially mediated by serotonergic mechanisms. PMID:20309529

  5. Determination of amphetamine and methamphetamine in umbilical cord using liquid chromatography-tandem mass spectrometry

    PubMed Central

    Jones, Joseph; Rios, Rosemarie; Jones, Mary; Lewis, Douglas; Plate, Charles

    2009-01-01

    The use of meconium as a drug-screening matrix for newborns has been the gold standard of care for the past two decades. A recent study using matched pairs of meconium and umbilical cord demonstrated a high degree of agreement. The use of liquid chromatography-tandem mass spectrometry as a means to confirm amphetamines presumptive positive umbilical cord specimens for amphetamine and methamphetamine is described here for the first time. The limit of detection for both compounds was 0.2 ng/g. The limit of quantitation for both compounds was 0.6 ng/g. The assay was linear for both compounds up to 100 ng/g. PMID:19783234

  6. Amphetamine induced dopamine release increases anxiety in individuals recovered from anorexia nervosa

    PubMed Central

    Bailer, Ursula F.; Narendran, Rajesh; Frankle, W. Gordon; Himes, Michael L; Duvvuri, Vikas; Mathis, Chester A; Kaye, W.H.

    2011-01-01

    Objective Genetic, pharmacologic, and physiological data suggest that individuals with anorexia nervosa (AN) have altered striatal dopamine (DA) function. Method We used an amphetamine challenge and positron emission tomography [11C]raclopride paradigm to explore DA striatal transmission in 10 recovered (REC) AN compared to 9 control women (CW). Results REC AN and CW were similar for baseline, post-amphetamine [11C]raclopride binding potential (BPND) and change (Δ) in BPND for all regions. In CW, ventral striatum Δ BPND was associated with euphoria (r = − .76; p = .03), which was not found for REC AN. Instead, REC AN showed a significant relationship between anxiety and Δ BPND in the pre-commissural dorsal caudate (r = −.62, p = .05). Discussion REC AN have a positive association between endogenous DA release and anxiety in the dorsal caudate. This finding could explain why food-related DA release produces anxiety in AN, whereas feeding is pleasurable in healthy participants. PMID:21541980

  7. Repeated exposures intensify rather than diminish the rewarding effects of amphetamine, morphine, and cocaine.

    PubMed

    Lett, B T

    1989-01-01

    It is commonly believed that repeated exposures diminish the pleasurable effects of drugs and hence that pleasure must have only a minor role in addiction. In six experiments with rats, repeated exposures to amphetamine, morphine, or cocaine were found to enhance the drug-induced rewarding effect as measured by conditioned place preference. Thus, sensitization to the rewarding effect, rather than tolerance, was obtained. Also, cross-sensitization was obtained; exposures to amphetamine enhanced the rewarding effect of morphine and vice versa; similarly, exposures to morphine enhanced the rewarding effect of cocaine. These findings support a new theory: drugs of abuse are addictive because repeated exposures sensitize the central reward mechanism so that drug taking produces a progressively greater reinforcing effect each time it occurs.

  8. Differential effects of scopolamine and amphetamine on microcomputer-based performance tests

    NASA Technical Reports Server (NTRS)

    Kennedy, Robert S.; Odenheimer, Robert C.; Baltzley, Dennis R.; Dunlap, William P.; Wood, Charles D.

    1990-01-01

    The effects of four weekly treatments with scopolamine (1.0 mg) and d-amphetamine (10 mg), separately or in combination, on human performance were investigated in 16 subjects undergoing nine performance tests from a menu of microcomputer-based tests administered after the treatment. It was d-amphetamine treatment that enhanced the results of motor and perceptual speed tests, while scopolamine had no effect on these tests. Two of the five cognitive tests showed reductions with scopolamine. The effects of scopolamine in this and other studies are considered in terms of a model which implies that the magnitude of the performance deficit depends on the performance type and the dosage level of the drug.

  9. Effects of d-amphetamine, methaqualone, and phencyclidine on the reaction time of pigeons.

    PubMed

    Kaczor, T; Blakely, E; Poling, A

    1993-06-01

    The effects of acute administrations of d-amphetamine (0.56, 1.0, 1.78, 3.2, and 5.6 mg/kg), methaqualone (5.6, 10, 18, 32, and 56 mg/kg), and phencyclidine (0.3, 0.56, 1.0, and 1.78 mg/kg) on the reaction time of pigeons were examined. In the reaction time assay, birds were trained to depress and hold a foot treadle until a stimulus change occurred. Releases within 2 s of the stimulus change were reinforced with food; premature releases or releases occurring after the 2-s limited hold were not reinforced. At relatively high doses, each of the drugs decreased the percentage of responses that were reinforced. Methaqualone and phencyclidine usually increased median reaction times at these doses, whereas the effects of d-amphetamine on reaction time were less clear.

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

    PubMed

    Al Shehri, Mohammed A; Youssef, Ali A

    2016-07-01

    A 35-year-old man of average build and a smoker, with a background of a psychiatric disorder, was brought by his neighbor to the emergency department after an hour of severe chest pain. Upon arrival at the hospital he had cardiac arrest, was resuscitated, and moved to the catheterization laboratory with inferior, posterior, and lateral myocardial infarction. Coronary angiography showed an unusual thrombosis in multiple coronary branches. Toxicology report showed high levels of amphetamines and benzodiazepines in the patient's original blood sample. The patient was kept under ventilation for 18 days, with difficult recovery due to severe withdrawal manifestations, ventilation acquired pneumonia, and rhabdomyolysis inducing acute renal failure. The patient regained near normal left ventricular function after baseline severe regional and global dysfunction. We postulate a relationship between the use of amphetamines, potentiated by benzodiazepines, and occurrence of acute thrombosis of multiple major coronary arteries. PMID:27358538

  11. Amphetamine-Type Stimulants: The Early History of Their Medical and Non-Medical Uses.

    PubMed

    Rasmussen, Nicolas

    2015-01-01

    Amphetamine was discovered as a drug in the late 1920s, and its pharmacological effects on attention and cognition, emotions, and appetite were explored thoroughly in the 1930s and 1940s. By the late 1940s, it had achieved medical and market success as an antidepressant and was quickly gaining such success as a diet medication. In contrast, both careful testing and extensive military experience had left the impression that the drugs' benefits for attention and cognition were more subjective than real and that any objective benefits were explained mainly by the drug's mood-elevating effects. Because of its unpatentable status, methamphetamine had been introduced for all the same uses by drug firms competing with the holder of the amphetamine patent. The drugs were being widely used nonmedically and their abuse potential was becoming recognized by medicine, eventually leading to their strict control internationally around 1970.

  12. Fetal alcohol syndrome

    MedlinePlus

    Alcohol in pregnancy; Alcohol-related birth defects; Fetal alcohol effects; FAS ... varies. Almost none of these babies have normal brain development. Infants and children with fetal alcohol syndrome have many different problems, which can be ...

  13. Fetal Alcohol Spectrum Disorders

    MedlinePlus

    ... alcohol can cause a group of conditions called fetal alcohol spectrum disorders (FASDs). Effects can include physical and behavioral problems such ... alcohol syndrome is the most serious type of FASD. People with fetal alcohol syndrome have facial abnormalities, ...

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

    PubMed

    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.

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

    PubMed Central

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

    2013-01-01

    Rationale Social play behavior is a characteristic form of social behavior displayed by juvenile and adolescent mammals. This social play behavior is highly rewarding, and of major importance for social and cognitive development. Social play is known to be modulated by neurotransmitter systems involved in reward and motivation. Interestingly, psychostimulant drugs, such as amphetamine and cocaine, profoundly suppress social play, but the neural mechanisms underlying these effects remain to be elucidated. Objective In this study we investigated the pharmacological underpinnings of amphetamine- and cocaine-induced suppression of social play behavior in rats. Results The play-suppressant effects of amphetamine were antagonized by the alpha-2 adrenoreceptor antagonist RX821002 but not by the dopamine receptor antagonist alpha-flupenthixol. Remarkably, the effects of cocaine on social play were not antagonized by alpha-2 noradrenergic, dopaminergic or serotonergic receptor antagonists, administered either alone or in combination. The effects of a subeffective dose of cocaine were enhanced by a combination of subeffective doses of the serotonin reuptake inhibitor fluoxetine, the dopamine reuptake inhibitor GBR12909 and the noradrenaline reuptake inhibitor atomoxetine. Conclusions Amphetamine, like methylphenidate, exerts its play-suppressant effect through alpha-2 noradrenergic receptors. On the other hand, cocaine reduces social play by simultaneous increases in dopamine, noradrenaline and serotonin neurotransmission. In conclusion, psychostimulant drugs with different pharmacological profiles suppress social play behavior through distinct mechanisms. These data contribute to our understanding of the neural mechanisms of social behavior during an important developmental period, and of the deleterious effects of psychostimulant exposure thereon. PMID:24057815

  16. Dopaminergic and noradrenergic substrates of positive reinforcement: differential effects of d- and l-amphetamine.

    PubMed

    Phillips, A G; Fibiger, H C

    1973-02-01

    Intracranial self-stimulation was elicited from electrodes located in either the lateral hypothalamus or substantia nigra of the rat. Facilitatory effects of d- and l-isomers of amphetamine on self-stimulation were assessed. The d-isomer was seven to ten times more effective than the l-isomer at the hypothalamic placement, whereas the two isomers were equipotent for substantia nigra electrodes. These data support the hypothesis that both dopaminergic and noradrenergic systems subserve positive reinforcement.

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

    PubMed Central

    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

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

    PubMed

    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.

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

    PubMed

    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. PMID:24913801

  20. Health promotion: Alcohol and drug misuse prevention.

    PubMed

    1983-01-01

    Currently, average apparent consumption of alcohol for all persons older than 14 is 10 percent higher than 10 years ago, and is equivalent to about 2.75 gallons of ethanol per person per year. Approximately 10 million adult Americans (i.e., 7 percent of those 18 or older) can be considered problem drinkers. Youthful problem drinkers, aged 14 to 17, are estimated to number more than 3 million and comprise 19 percent of this age group. In addition to the social costs, the economic costs to society as a result of alcohol misuse are substantial--an estimated +49.4 billion in 1977. Ten percent of all deaths in the United States are alcohol-related. Cirrhosis, which is largely attributable to alcohol consumption, ranks among the 10 leading causes of death. Alcohol use also is associated with cancer of the liver, pancreas, esophagus, and mouth. Alcohol consumption during pregnancy is associated with a wide range of possible harmful effects to the fetus--among them decreased birth weight, spontaneous abortion, and physical and mental birth defects. Drug misuse is also an expanding problem. There are some 16 million current marijuana users. The popularity of cocaine continues to increase--over 10 million Americans have tried cocaine at least once and there are an estimated 1 to 2 million current users. Misuse of barbiturates remains a significant problem with at least 1 million persons believed to misuse these drugs and the 30,000 estimated to be addicted to them. In addition, heroin addiction is still considered by many to be the most serious drug problem in the United States. Drug misuse leads to a number of social and health problems. Excessive doses of depressants can result in both physical and psychological dependence. The toll from heroin includes premature death and severe disability, family disruption, and crime committed to maintain the habit. Misuse of hallucinogens often results in emergency room visits. A special problem is the relationship of marijuana to

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

    PubMed Central

    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

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

    PubMed

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

    1999-01-01

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

  3. DPP IV inhibitor blocks mescaline-induced scratching and amphetamine-induced hyperactivity in mice.

    PubMed

    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.

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

    PubMed

    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. PMID:26419092

  5. Determination of amphetamines in biological samples using electro enhanced solid-phase microextraction-gas chromatography.

    PubMed

    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.

  6. Amphetamine binding to synthetic melanin and scatchard analysis of binding data.

    PubMed

    Gautam, Lata; Scott, Karen S; Cole, Michael D

    2005-01-01

    Previous research into drug-hair binding shows that hair color affects drug-hair binding. There are no structural disparities in hair of different colors other than the type and content of melanin present. For this reason, this investigation focuses on synthetic eumelanin as a site for drug interaction using amphetamine as the candidate drug. The binding study was carried out at room temperature. The interaction between synthetic eumelanin and amphetamine was monitored using UV-Vis spectrophotometry at 257.2 nm. As the molecular weight of melanin is unknown, the number of binding sites could not be calculated directly. Hence the ratio of the number of mumoles of drug bound and the dry weight of melanin in mug was considered. Equilibrium was reached when approximately 32% of the drug was bound to melanin. Hence this study proves that amphetamine binds to synthetic eumelanin in vitro. Data interpretation using Scatchard analysis yielded a curvilinear plot with upward concavity indicating multiple binding sites on melanin and negative cooperativity. PMID:16105258

  7. Temporal concordance of anorectic, behavioral, cardiovascular and amphetamine receptor binding activity of phenethylamines in rats

    SciTech Connect

    Borrelli, A.; Blosser, J.; Barrantes, M.; Colombo, P.; Kinsolving, C.R.; Ordy, M.; Watkins, B.

    1986-03-01

    Although numerous studies have described the anorectic, cardiovascular, and behavioral effects of phenthylamines, a comparison of the pharmacological concordance of these properties in a single species is needed. The objectives of this study were to compare the anorectic potency of 13 phenethylamines following po administration with their effects on spontaneous locomotor activity (SLA) and blood pressure (BP) in vivo and with amphetamine receptor affinity in vitro. The anorectic potencies (ED 50) ranged from 12 umol/kg (fenfluramine) to over 400 umol/kg (d-norephedrine and 1-pseudoephedrine). d-Amphetamine, phentermine, and d-norpseudoephedrine were among the most active and 1-pseudoephedrine and 1-nor-ephedrine the least active in increasing SLA. 1-Norephedrine, and d-norpseudoephedrine were the most active increasing BP while d-norephedrine produced a weak vasodepressor effect. A significant correlation (r = .80) was observed between anorectic potency and affinity (IC 50) for /sup 3/H-amphetamine binding sites in the hypothalamus. However, the stereoselectivity between pairs of enantiomers to inhibit food consumption was not paralleled in binding affinity. The rank order of concordance of phenethylamines in anorectic activity was most apparent in behavior and binding affinity.

  8. Reference region modeling approaches for amphetamine challenge studies with [11C]FLB 457 and PET.

    PubMed

    Sandiego, Christine M; Gallezot, Jean-Dominique; Lim, Keunpoong; Ropchan, Jim; Lin, Shu-fei; Gao, Hong; Morris, Evan D; Cosgrove, Kelly P

    2015-04-01

    Detecting fluctuations in synaptic dopamine levels in extrastriatal brain regions with [(11)C]FLB 457 and positron emission tomography (PET) is a valuable tool for studying dopaminergic dysfunction in psychiatric disorders. The evaluation of reference region modeling approaches would eliminate the need to obtain arterial input function data. Our goal was to explore the use of reference region models to estimate amphetamine-induced changes in [(11)C]FLB 457 dopamine D2/D3 binding. Six healthy tobacco smokers were imaged with [(11)C]FLB 457 at baseline and at 3 hours after amphetamine (0.4 to 0.5 mg/kg, per os) administration. Simplified reference tissue models, SRTM and SRTM2, were evaluated against the 2-tissue compartmental model (2TC) to estimate [(11)C]FLB 457 binding in extrastriatal regions of interest (ROIs), using the cerebellum as a reference region. No changes in distribution volume were observed in the cerebellum between scan conditions. SRTM and SRTM2 underestimated binding, compared with 2TC, in ROIs by 26% and 9%, respectively, with consistent bias between the baseline and postamphetamine scans. Postamphetamine, [(11)C]FLB 457 binding significantly decreased across several brain regions as measured with SRTM and SRTM2; no significant change was detected with 2TC. These data support the sensitivity of [(11)C]FLB 457 for measuring amphetamine-induced dopamine release in extrastriatal regions with SRTM and SRTM2. PMID:25564239

  9. Amphetamine binding to synthetic melanin and scatchard analysis of binding data.

    PubMed

    Gautam, Lata; Scott, Karen S; Cole, Michael D

    2005-01-01

    Previous research into drug-hair binding shows that hair color affects drug-hair binding. There are no structural disparities in hair of different colors other than the type and content of melanin present. For this reason, this investigation focuses on synthetic eumelanin as a site for drug interaction using amphetamine as the candidate drug. The binding study was carried out at room temperature. The interaction between synthetic eumelanin and amphetamine was monitored using UV-Vis spectrophotometry at 257.2 nm. As the molecular weight of melanin is unknown, the number of binding sites could not be calculated directly. Hence the ratio of the number of mumoles of drug bound and the dry weight of melanin in mug was considered. Equilibrium was reached when approximately 32% of the drug was bound to melanin. Hence this study proves that amphetamine binds to synthetic eumelanin in vitro. Data interpretation using Scatchard analysis yielded a curvilinear plot with upward concavity indicating multiple binding sites on melanin and negative cooperativity.

  10. Behavioral sensitization following concurrent exposure to mephedrone and D-amphetamine in female mice.

    PubMed

    Berquist, Michael D; Peet, M Melissa; Baker, Lisa E

    2015-02-01

    Recreational use of illicit methcathinone derivatives is a public health concern in the USA and Europe. Recent reports indicate that mephedrone (MEPH) produces neurochemical and behavioral effects comparable with amphetamines. The present study investigated the effects of a mixture of MEPH and D-amphetamine (AMPH) on the induction and expression of behavioral sensitization. Thirty female CD-1 mice received seven subcutaneous injections of saline, AMPH (1.0 mg/kg), MEPH (3.0 mg/kg), or AMPH (1.0 mg/kg)+MEPH (3.0 mg/kg) over an 8-day period with 48 h between the first and second injection and 24 h between subsequent injections. Activity was assessed immediately following the first and seventh dose. After a 10-day washout, 1.0 mg/kg AMPH was administered to all animals and activity was assessed in a similar manner. Compared with mice treated with AMPH or MEPH, those treated with AMPH+MEPH displayed stronger indices of behavioral sensitization after the seventh dose and in response to AMPH after the washout period. These results suggest that MEPH may enhance sensitivity to the behavioral effects of AMPH. Considered in light of findings that MEPH has comparable neurochemical actions to the amphetamines and is commonly used with other stimulants, further research on the abuse liability of drug mixtures with methcathinones and other psychostimulants is warranted.

  11. Allyl alcohol

    Integrated Risk Information System (IRIS)

    Allyl alcohol ; CASRN 107 - 18 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  12. Propargyl alcohol

    Integrated Risk Information System (IRIS)

    Propargyl alcohol ; CASRN 107 - 19 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  13. Isobutyl alcohol

    Integrated Risk Information System (IRIS)

    Isobutyl alcohol ; CASRN 78 - 83 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  14. Alcohol project

    SciTech Connect

    Not Available

    1980-12-01

    The Great Western Sugar Company has announced plans for the construction of a $300 million plant for the production of fuel grade alcohol from corn. The plant at Reserve, Lousiana, will also produce high fructose corn syrup and animal feed by-products and will employ an additional 200 people.

  15. Alcoholism and Minority Populations.

    ERIC Educational Resources Information Center

    Watts, Thomas D.; Wright, Roosevelt, Jr.

    1991-01-01

    Briefly discusses some aspects of the role of the state and the position of minorities in respect to alcoholism policies and services. Includes case study of a Black alcoholic. Refers readers to studies on Black alcoholism, Native American alcoholism, Hispanic alcoholism, and Asian-American alcoholism. (Author/NB)

  16. Testosterone attenuates and the selective estrogen receptor modulator, raloxifene, potentiates amphetamine-induced locomotion in male rats.

    PubMed

    Purves-Tyson, Tertia D; Boerrigter, Danny; Allen, Katherine; Zavitsanou, Katerina; Karl, Tim; Djunaidi, Vanezha; Double, Kay L; Desai, Reena; Handelsman, David J; Weickert, Cynthia Shannon

    2015-04-01

    Although sex steroids are known to modulate brain dopamine, it is still unclear how testosterone modifies locomotor behaviour controlled, at least in part, by striatal dopamine in adolescent males. Our previous work suggests that increasing testosterone during adolescence may bias midbrain neurons to synthesise more dopamine. We hypothesised that baseline and amphetamine-induced locomotion would differ in adult males depending on testosterone exposure during adolescence. We hypothesised that concomitant stimulation of estrogen receptor signaling, through a selective estrogen receptor modulator (SERM), raloxifene, can counter testosterone effects on locomotion. Male Sprague-Dawley rats at postnatal day 45 were gonadectomised (G) or sham-operated (S) prior to the typical adolescent testosterone increase. Gonadectomised rats were either given testosterone replacement (T) or blank implants (B) for six weeks and sham-operated (i.e. intact or endogenous testosterone group) were given blank implants. Subgroups of sham-operated, gonadectomised and gonadectomised/testosterone-replaced rats were treated with raloxifene (R, 5mg/kg) or vehicle (V), daily for the final four weeks. There were six groups (SBV, GBV, GTV, SBR, GBR, GTR). Saline and amphetamine-induced (1.25mg/kg) locomotion in the open field was measured at PND85. Gonadectomy increased amphetamine-induced locomotion compared to rats with endogenous or with exogenous testosterone. Raloxifene increased amphetamine-induced locomotion in rats with either endogenous or exogenous testosterone. Amphetamine-induced locomotion was negatively correlated with testosterone and this relationship was abolished by raloxifene. Lack of testosterone during adolescence potentiates and testosterone exposure during adolescence attenuates amphetamine-induced locomotion. Treatment with raloxifene appears to potentiate amphetamine-induced locomotion and to have an opposite effect to that of testosterone in male rats.

  17. Chronic variable stress prevents amphetamine-elicited 50-kHz calls in rats with low positive affectivity.

    PubMed

    Kõiv, Kadri; Metelitsa, Mait; Vares, Marten; Tiitsaar, Kai; Raudkivi, Karita; Jaako, Külli; Vulla, Kaspar; Shimmo, Ruth; Harro, Jaanus

    2016-04-01

    The relationship between stress response and positive affective states is thought to be bidirectional: whilst stress can lead to a blunted hedonic response, positive affect reduces the negative effects of stress. We have previously shown that persistently high positive affectivity as measured by 50-kHz ultrasonic vocalizations (USVs) is protective against chronic variable stress (CVS). The present study examined the effect of CVS on 50-kHz USVs elicited by amphetamine administration, simultaneously considering the stable inter-individual differences in positive affectivity. Forty juvenile male Wistar rats were categorised as of high (HC) or low (LC) positive affectivity based on their 50-kHz USV response to imitation of rough-and-tumble play ('tickling'). As adults, the rats were subjected to four weeks of CVS, after which D-amphetamine was administered in five daily doses followed by a challenge dose (all 1mg/kg IP) nine days later. CVS reduced sucrose preference in LC-rats only. After CVS, amphetamine-elicited 50-kHz USVs were significantly reduced in LC-rats, the effect of stress in HC-rats being smaller and less consistent. In previously stressed and amphetamine-treated LC-rats, locomotor response to amphetamine was attenuated. In stressed LC-rats, DOPAC levels and dopamine turnover were increased in striatum after amphetamine treatment, and dopamine D1 receptor levels were upregulated in nucleus accumbens. LC-rats had lower isoleucine levels in frontal cortex. These results show that stress-related changes in response to amphetamine are dependent on inter-individual differences in positive affectivity both at neurochemical and behavioural levels, and further support the notion of higher vulnerability of animals with low positive affect.

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

    PubMed

    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.

  19. Evidence for Fibroblast Growth Factor-2 as a Mediator of Amphetamine-Enhanced Motor Improvement following Stroke

    PubMed Central

    Wolf, William A.; Martin, Jody L.; Kartje, Gwendolyn L.; Farrer, Robert G.

    2014-01-01

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

  20. Interstellar Alcohols

    NASA Technical Reports Server (NTRS)

    Charnley, S. B.; Kress, M. E.; Tielens, A. G. G. M.; Millar, T. J.

    1995-01-01

    We have investigated the gas-phase chemistry in dense cores where ice mantles containing ethanol and other alcohols have been evaporated. Model calculations show that methanol, ethanol, propanol, and butanol drive a chemistry leading to the formation of several large ethers and esters. Of these molecules, methyl ethyl ether (CH3OC2H5) and diethyl ether (C2H5)2O attain the highest abundances and should be present in detectable quantities within cores rich in ethanol and methanol. Gas-phase reactions act to destroy evaporated ethanol and a low observed abundance of gas-phase C,H,OH does not rule out a high solid-phase abundance. Grain surface formation mechanisms and other possible gas-phase reactions driven by alcohols are discussed, as are observing strategies for the detection of these large interstellar molecules.

  1. Alcohol use and safe drinking

    MedlinePlus

    ... RISKS OF ALCOHOL Alcohol increases the risk of: Alcoholism Falls, drownings, and other accidents Head, neck, stomach, ... pubmed/23698791 . National Institute on Alcohol Abuse and Alcoholism. Alcohol and your health. www.niaaa.nih.gov/ ...

  2. Amphetamine and morphine may produce acute-withdrawal related hypoactivity by initially activating a common dopamine pathway.

    PubMed

    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

  3. Estimation of gamma-hydroxybutyrate (GHB) co-consumption in serum samples of drivers positive for amphetamine or ecstasy.

    PubMed

    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.

  4. Changes in striatal D2-receptor density following chronic treatment with amphetamine as assessed with PET in nonhuman primates.

    PubMed

    Ginovart, N; Farde, L; Halldin, C; Swahn, C G

    1999-02-01

    Recent brain imaging studies suggest that schizophrenia may be related to abnormally high amphetamine-induced dopamine release. It is known that repeated use of amphetamine may cause paranoid psychosis and persisting stereotypies. The biochemical background for these signs and symptoms has not been clarified. In this study, positron emission tomography and [11C]raclopride were used to determine central D2-dopamine receptor density (Bmax) and apparent affinity (K(D)app) in Cynomolgus monkeys before and after 14 days of treatment with d-amphetamine sulphate (2 mg/kg/day; s.c.). One day after withdrawal from amphetamine, K(D)app was increased, suggesting [11C]raclopride competition with elevated concentration of dopamine. At 7 and 14 days after withdrawal, there was a 19-26% decrease in Bmax but no change in K(D)app as compared to baseline. Although this study was performed on two monkeys only, there was thus no support for the view that chronic intermittent hyperactivity of the dopamine system may be related to an upregulation of striatal D2-dopamine receptors. Repeated administration of amphetamine may, rather, cause a long-lasting downregulation of the D2-receptor density, which may be a neurochemical correlate to the abnormal movements, anhedonia, anxiety, and depression seen in psychostimulant abusers.

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

    PubMed

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

    2015-10-15

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

  6. Axonal plasticity is associated with motor recovery following amphetamine treatment combined with rehabilitation after brain injury in the adult rat.

    PubMed

    Ramic, Maya; Emerick, April J; Bollnow, Melanie R; O'Brien, Timothy E; Tsai, Shih-Yen; Kartje, Gwendolyn L

    2006-09-21

    Clinical and laboratory studies have suggested that amphetamine treatment when paired with rehabilitation results in improved recovery of function after stroke or traumatic brain injury. In the present study, we investigated whether new anatomical pathways developed in association with improved motor function after brain damage and amphetamine treatment linked with rehabilitation. Following a unilateral sensorimotor cortex lesion in the adult rat, amphetamine (2 mg/kg) was administered in conjunction with physiotherapy sessions on postoperative days two and five. Physiotherapy was continued twice daily for the first 3 weeks after injury, and then once daily until week six. Performance on skilled forelimb reaching and ladder rung walking was used to assess motor improvement. Our results show that animals with sensorimotor cortical lesions receiving amphetamine treatment linked with rehabilitation had significant improvement in both tasks. Neuroanatomical tracing of efferent pathways from the opposite, non-damaged cortex resulted in the novel finding that amphetamine treatment linked with rehabilitation, significantly increased axonal growth in the deafferented basilar pontine nuclei. These results support the notion that pharmacological interventions paired with rehabilitation can enhance neuronal plasticity and thereby improve functional recovery after CNS injury. PMID:16920088

  7. The rate of intravenous cocaine or amphetamine delivery: influence on drug-taking and drug-seeking behavior in rats

    PubMed Central

    Crombag, Hans S.; Ferrario, Carrie R.; Robinson, Terry E.

    2008-01-01

    We studied the influence of rate of intravenous infusion of cocaine or amphetamine on drug-taking and seeking behavior. First, drug-naive rats were tested for acquisition of self-administration of increasing doses of amphetamine or cocaine infused over 5 or 100s. Second, self-administration of cocaine or amphetamine infused over 5–100 sec was assessed on fixed or progressive-ratio (PR) reinforcement schedules. Finally, the ability of a single 5 or 100 sec amphetamine or cocaine infusion to reinstate extinguished drug seeking was assessed. Although slower infusion rates produced a small effect on drug taking under continuous-reinforcement conditions, infusion rate did not alter drug taking on intermittent or PR reinforcement schedules, or the ability of cocaine or amphetamine to reinstate drug seeking. Taken together, our results suggest that variation in drug delivery rate over a range that we previously found alters the induction of behavioral sensitization, gene-expression and striatal dopamine activity, does not markedly alter drug-taking or seeking behavior. PMID:18586051

  8. Separation mechanism of chiral impurities, ephedrine and pseudoephedrine, found in amphetamine-type substances using achiral modifiers in the gas phase.

    PubMed

    Holness, Howard K; Jamal, Adeel; Mebel, Alexander; Almirall, José R

    2012-11-01

    A new mechanism is proposed that describes the gas-phase separation of chiral molecules found in amphetamine-type substances (ATS) by the use of high-resolution ion mobility spectrometry (IMS). Straight-chain achiral alcohols of increasing carbon chain length, from methanol to n-octanol, are used as drift gas modifiers in IMS to highlight the mechanism proposed for gas-phase separations of these chiral molecules. The results suggest the possibility of using these achiral modifiers to separate the chiral molecules (R,S) and (S,R)-ephedrine and (S,S) and (R,R)-pseudoephedrine which contain an internal hydroxyl group at the first chiral center and an amino group at the other chiral center. Ionization was achieved with an electrospray source, the ions were introduced into an IMS with a resolving power of 80, and the resulting ion clusters were characterized with a coupled quadrupole mass spectrometer detector. A complementary computational study conducted at the density functional B3LYP/6-31g level of theory for the electronic structure of the analyte-modifier clusters was also performed, and showed either "bridged" or "independent" binding. The combined experimental and simulation data support the proposed mechanism for gas-phase chiral separations using achiral modifiers in the gas phase, thus enhancing the potential to conduct fast chiral separations with relative ease and efficiency.

  9. [Alcohol and alcoholism: attitudes of nursing students].

    PubMed

    Vargas, Divane; Bittencourt, Marina Nolli

    2013-01-01

    This is a descriptive exploratory study that aimed to verify nursing students' attitudes facing to the alcoholic drinks, alcoholism and alcoholics, according to their position in face of an attitudes scale items. For data collection, it was used the Scale of Attitudes to alcohol, alcoholism and alcoholic, applied to 144 nursing students. The results showed a tendency to negative attitudes of these students in face of alcoholism, alcoholic person and alcoholic drinks, since most participants were placed in category indifferent or disagree with the positive items, agreeing with negative scale items. We conclude that this trend of negative attitudes is connected to insufficient attention given to the subject during the nurses' education, being verified the need for greater importance to be given to this problem.

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

    PubMed Central

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

    2014-01-01

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

  11. Gestational Toluene Exposure Effects on Spontaneous and Amphetamine-Induced Locomotor Behavior in Rats

    PubMed Central

    Mohammadi, Michael H.; Batis, Jeffery C.; Hannigan, John H.

    2007-01-01

    The abuse of volatile organic solvents (inhalants) continues to be a major health concern throughout the world. Toluene, which is found in many products such as glues and household cleaners, is among the most commonly abused organic solvents. The neurobehavioral teratogenic sequelae of solvent abuse (i.e., repeated, brief inhalation exposures to very high concentrations of solvents) have not been examined thoroughly. In a preclinical model of inhalant abuse, timed-pregnant Sprague-Dawley rats were exposed to 0, 8,000, or 12,000 parts per million (ppm) for 15 min twice daily from gestation day 8 (GD8) through GD20. In the first experiment, separate groups of offspring were observed individually in an open-field on postnatal day 22 (PN22), PN42 or PN63. In the second experiment, other offspring given identical prenatal toluene exposures were observed in an “open-field” following an acute i.p. injection of amphetamine (0, 0.56, 1.78 mg/kg) on PN28. Automated measurements of distance traveled and ambulatory time were recorded. Prenatal toluene exposure resulted in small alterations in spontaneous activity compared to non-exposed rats. Prenatal exposure to 12,000 ppm toluene resulted in significant hyposensitivity to the locomotor stimulatory effects of the amphetamine challenge in male but not female rats on PN28. The results demonstrate that prenatal exposure to abuse patterns of high concentrations of toluene through inhalation can alter spontaneous and amphetamine-induced locomotor behavior in rats. The expression of these effects also appears to depend upon the postnatal age of testing. These results imply that abuse of organic solvents during pregnancy in humans may also produce long-lasting effects on biobehavioral development. PMID:17112700

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

    PubMed

    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.

  13. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder.

    PubMed

    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.

  14. Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. I. Saturable sequestration

    SciTech Connect

    Zaczek, R.; Culp, S.; Goldberg, H.; Mccann, D.J.; De Souza, E.B. )

    1991-05-01

    Previous studies have identified a saturable site of d-({sup 3}H)amphetamine sequestration (AMSEQ) in rat brain synaptosomes. The present study characterized AMSEQ with respect to its subcellular, neuronal and regional distributions, ontogenetic development, pharmacological specificity and factors required for its maintenance. Although AMSEQ was reduced when assays were performed in Krebs' buffer incubated at 37{degree}C as compared to assays performed in isotonic Tris-sucrose buffer incubated at room temperature, the pharmacological profiles of AMSEQ were virtually identical under both conditions. AMSEQ was negligible in tissues outside the central nervous system, enriched in synaptosomes and partially reduced by striatal kainic acid lesion, indicating neuronal localization. The distribution of AMSEQ in the central nervous system was heterogenous. Highest levels were present in hypothalamus with progressively lower levels noted in parietal cortex, frontal cortex, striatum, thalamus, hippocampus, midbrain, cerebellum, pons-medulla and spinal cord. With regard to its ontogeny, AMSEQ increased early in neonatal life, reaching adult levels by postnatal day 14. Although the effects of amphetamine to abolish the transynaptosomal pH gradient suggest a possible role for this gradient in the maintenance of AMSEQ, the pharmacological profile of AMSEQ indicates that other factors are involved. An interaction with an intrasynaptosomal acid, such as N-acetylaspartate, may account for AMSEQ maintenance. AMSEQ did not possess a stereospecific preference for either d-(IC50 = 177 microM) or I-amphetamine (IC50 = 173 microM). However, the pharmacological profile of AMSEQ indicated structural specificity with antidepressants being relatively potent inhibitors. (Abstract Truncated)

  15. Effects of amphetamine, morphine, and CP 55, 940 on Go/No-Go task performance in rhesus monkeys.

    PubMed

    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. PMID:26061355

  16. Increased locomotor response to novelty and propensity to intravenous amphetamine self-administration in adult offspring of stressed mothers.

    PubMed

    Deminière, J M; Piazza, P V; Guegan, G; Abrous, N; Maccari, S; Le Moal, M; Simon, H

    1992-07-17

    It is suggested that drug addiction is more likely to develop in individuals who are particularly sensitive to the reinforcing effects of drugs. Animal studies of intravenous drug self-administration (SA) have shown that rats display a large range of individual differences in the propensity to develop drug-seeking. Predisposed animals are characterized by a higher locomotor reactivity to both novelty and psychostimulants. In this report, we show that prenatal stress (restraint of the mother during the last week of pregnancy) may contribute to an individual's vulnerability to develop amphetamine self-administration. The adult offspring of stressed mothers exhibited: (i) a higher locomotor response to novelty and to an injection of amphetamine (0.3 mg/kg, i.v.); (ii) a higher level of amphetamine self-administration. The data indicate that individual predisposition to drug-seeking in the adult may be induced by prenatal events. PMID:1511342

  17. Ethanol, nicotine, amphetamine, and aspartame consumption and preferences in C57BL/6 and DBA/2 mice.

    PubMed

    Meliska, C J; Bartke, A; McGlacken, G; Jensen, R A

    1995-04-01

    Using a two-bottle choice paradigm, adult C57BL/6 and DBA/2 mice (11 males an 10 females per strain) were given access to tapwater and an ascending series of concentrations of ethanol, nicotine, amphetamine, and th artificial sweetener, aspartame. The C57 mice consumed more ethanol, nicotine, and amphetamine, and showed greater preferences for these substances, than did the DBA/2 mice. In contrast, DBAs consumed more and showed greater preference for aspartame than C57s. However, measures of drug and aspartame consumption and preference were moderately intercorrelated when the effects of gender and strain were controlled for. This pattern of results suggests that factors modulating differences between C57BL/6 and DBA/2 mice in ethanol consumption and preference also modulate differences in consumption of nicotine and amphetamine.

  18. [AWMF-guideline: cocaine-, amphetamine-, ecstasy- and hallucinogen-related disorders].

    PubMed

    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.

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

    PubMed

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

    2016-08-01

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

  20. Amphetamine with experience promotes recovery of locomotor function after unilateral frontal cortex injury in the cat.

    PubMed

    Hovda, D A; Fenney, D M

    1984-04-30

    In cats, a single dose of D-amphetamine (AMP) given at 10 days after unilateral frontal cortex ablation produced an immediate and enduring (60 day) acceleration of beam-walking ability compared to saline control animals. Four doses of AMP at 4-day intervals promoted recovery faster than a single dose of AMP. Subjects with no beam-walking experience while under AMP intoxication were not different from saline controls after two doses of AMP. However, after 4 doses these cats recovered significantly faster than saline controls and were comparable to animals that received AMP and experience under the drug. PMID:6722561

  1. Superior Mesenteric Artery Syndrome Associated with Rapid Weight Loss Attributed to Amphetamine Abuse

    PubMed Central

    Fazio, Richard M.; Chen, On; Eldarawy, Wael

    2015-01-01

    Superior mesenteric artery (SMA) syndrome arises from a reduction in the angle formed between the SMA and the aorta, thereby compressing the third portion of the duodenum. This phenomenon may be caused by a number of factors, one of which being acute weight loss. We report a case of a female patient presenting with abdominal pain and vomiting who developed superior mesenteric artery (SMA) syndrome as a result of rapid weight loss, thought to be secondary to amphetamine abuse. This association can often be overlooked and, to our knowledge, has not been previously reported. PMID:26351593

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

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

    2014-01-01

    Withdrawal from amphetamine increases anxiety and reduces the ability to cope with stress, factors that are believed to contribute to drug relapse. Stress-induced serotonergic transmission in the central nucleus of the amygdala is associated with anxiety states and fear. Conversely, increases in stress-induced ventral hippocampal serotonin have been linked to coping mechanisms. The goal of this study is to understand neurobiological changes induced by amphetamine that contribute to stress-sensitivity during withdrawal. We tested the hypothesis that limbic serotonergic responses to restraint stress would be altered in male Sprague-Dawley rats chronically pre-treated with amphetamine (2.5 mg/kg, ip.) followed by two weeks withdrawal. Amphetamine withdrawal resulted in increased stress-induced behavioral arousal relative to control treatment, suggesting that drug withdrawal induced a greater sensitivity to the stressor. When microdialysis was used to determine the effects of restraint on extracellular serotonin, stress-induced increases in serotonin were abolished in the ventral hippocampus and augmented in the central amygdala during amphetamine withdrawal. Reverse dialysis of the glucocorticoid receptor antagonist mifepristone into the ventral hippocampus blocked the stress-induced serotonin increase in saline pre-treated rats, suggesting that glucocorticoid receptors mediate stress-induced serotonin increases in the ventral hippocampus. However, mifepristone had no effect on stress-induced serotonin increases in the central amygdala, indicating that stress increases serotonin in this region independent of glucocorticoid receptors. During amphetamine withdrawal, the absence of stress-induced increases in ventral hippocampus serotonin combined with enhanced stress-induced serotonergic responses in the central amygdala may contribute to drug relapse by decreasing stress-coping ability and heightening stress responsiveness. PMID:25234335

  4. Non-parametric analysis of neurochemical effects and Arc expression in amphetamine-induced 50-kHz ultrasonic vocalization.

    PubMed

    Hamed, Adam; Daszczuk, Patrycja; Kursa, Miron Bartosz; Turzyńska, Danuta; Sobolewska, Alicja; Lehner, Małgorzata; Boguszewski, Paweł M; Szyndler, Janusz

    2016-10-01

    A number of studies have identified the importance of dopaminergic, opioid, serotonergic, noradrenergic and glutamatergic neurotransmission in amphetamine-induced "50-kHz" ultrasonic vocalizations (USVs). Amphetamine became a topic of interest for many researchers interested in USVs due to its ability to induce 50-kHz USVs. To date, it has been difficult to identify the neurotransmitters responsible for this phenomenon. The aim of this study was to determine the following: (i) concentrations of neurotransmitters in selected structures of the rat brain after re-exposure of the rats to amphetamine administration; (ii) changes in Arc in the medial prefrontal cortex, striatum, nucleus accumbens core and shell, hippocampus, amygdala and ventral tegmental area; and (iii) a biological basis for differences in 50-kHz USV emissions in response to amphetamine administration. Re-exposure to amphetamine increased 50-kHz USVs. This parameter do not correlate with distance covered by the investigated animals. An increased concentration of noradrenaline in the nucleus accumbens (NAcc) strongly correlated with the number of 50-kHz USVs. We found that NAcc noradrenaline concentrations negatively correlated with the concentration of dopamine and dopamine metabolites and positively correlated with the concentration of GABA and 5-HIAA (serotonin metabolite) in this structure. We have also identified a positive correlation between striatal 3-MT (dopamine metabolite) concentrations and Arc expression in the hippocampal DG as well as a negative correlation between the concentration of GABA in the amygdala and Arc expression in the central amygdala. Thus, the relationship between the emission of 50-kHz USVs and the neurochemical changes that occur after re-exposure to amphetamine indicates cross-talk between NA, DA, 5-HT and GABA neurotransmission in the NAcc.

  5. Non-parametric analysis of neurochemical effects and Arc expression in amphetamine-induced 50-kHz ultrasonic vocalization.

    PubMed

    Hamed, Adam; Daszczuk, Patrycja; Kursa, Miron Bartosz; Turzyńska, Danuta; Sobolewska, Alicja; Lehner, Małgorzata; Boguszewski, Paweł M; Szyndler, Janusz

    2016-10-01

    A number of studies have identified the importance of dopaminergic, opioid, serotonergic, noradrenergic and glutamatergic neurotransmission in amphetamine-induced "50-kHz" ultrasonic vocalizations (USVs). Amphetamine became a topic of interest for many researchers interested in USVs due to its ability to induce 50-kHz USVs. To date, it has been difficult to identify the neurotransmitters responsible for this phenomenon. The aim of this study was to determine the following: (i) concentrations of neurotransmitters in selected structures of the rat brain after re-exposure of the rats to amphetamine administration; (ii) changes in Arc in the medial prefrontal cortex, striatum, nucleus accumbens core and shell, hippocampus, amygdala and ventral tegmental area; and (iii) a biological basis for differences in 50-kHz USV emissions in response to amphetamine administration. Re-exposure to amphetamine increased 50-kHz USVs. This parameter do not correlate with distance covered by the investigated animals. An increased concentration of noradrenaline in the nucleus accumbens (NAcc) strongly correlated with the number of 50-kHz USVs. We found that NAcc noradrenaline concentrations negatively correlated with the concentration of dopamine and dopamine metabolites and positively correlated with the concentration of GABA and 5-HIAA (serotonin metabolite) in this structure. We have also identified a positive correlation between striatal 3-MT (dopamine metabolite) concentrations and Arc expression in the hippocampal DG as well as a negative correlation between the concentration of GABA in the amygdala and Arc expression in the central amygdala. Thus, the relationship between the emission of 50-kHz USVs and the neurochemical changes that occur after re-exposure to amphetamine indicates cross-talk between NA, DA, 5-HT and GABA neurotransmission in the NAcc. PMID:27288591

  6. Multivariate Analysis of Subjective Responses to d-amphetamine In Healthy Volunteers Finds Novel Genetic Pathway Associations

    PubMed Central

    Yarosh, Haley L.; Meda, Shashwath A.; de Wit, Harriet; Hart, Amy B.; Pearlson, Godfrey D.

    2015-01-01

    Rationale Researchers studying behavioral and physiologic effects of d-amphetamine have explored individual response differences to the drug. Concurrently, genome wide analyses have identified several single nucleotide polymorphisms (SNPs) associated with these traits. Univariate methods can identify SNPs associated with behavioral and physiological traits, but multivariate analyses allow identification of clusters of related biologically relevant SNPs and behavioral components. Objectives To identify clusters of related biologically relevant SNPs and behavioral components in the responses of healthy individuals to d-amphetamine using multivariate analysis. Methods Individuals (N=375) without substance abuse histories completed surveys and detailed cardiovascular monitoring during randomized, blinded sessions: d-amphetamine (10mg, 20mg), placebo. We applied parallel-independent component analysis (Para-ICA) to data previously analyzed with univariate approaches, revealing new associations between genes and behavioral responses to d-amphetamine. Results Three significantly associated (p<.001) phenotype-genotype pairs emerged. The first component included physiologic measures of systolic and diastolic blood pressure (BP) and mean arterial pressure (MAP) along with SNPs in calcium and glutamatergic signaling pathways. The second associated components included the ‘Anger’ items from the Profile of Mood States (POMS) questionnaire and the Marijuana effects from the Addiction Research Center Inventory (Cuyas, Verdejo-Garcia et al.), with enriched genetic pathways involved in Cardiomyopathy and MAPK signaling. The final pair included ‘Anxious’, ‘Fatigue’, and ‘Confusion’ items from the POMS questionnaire, plus functional pathways related to cardiac muscle contraction and cardiomyopathy. Conclusions Multifactorial genetic networks related to calcium signaling, glutamatergic and dopaminergic synapse function and amphetamine addiction appear to mediate common

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

    PubMed Central

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

    2011-01-01

    Individual differences that may contribute to vulnerability to abuse drugs have been identified. Sensation-seeking status has been shown to influence both vulnerability to drug use and response to acute drug administration. The purpose of the present experiment was to examine the reinforcing effects of d-amphetamine in high and low sensation-seeking subjects using a modified progressive-ratio procedure. A battery of subject-rated, performance, and cardiovascular measures was also included to better characterize the effects of d-amphetamine in these groups. Ten high sensation seekers and ten low sensation seekers that were matched for education, age, drug use, height, and weight, first sampled doses of d-amphetamine (0, 8, and 16 mg). In subsequent sessions, subjects were offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. d-Amphetamine functioned as a reinforcer and produced prototypical stimulant-like effects (e.g., increased subject-ratings of Like Drug, enhanced performance, and increased heart rate). High sensation seekers were more sensitive than low sensation seekers to the reinforcing and some of the subject-rated effects of d-amphetamine. The results of the present experiment extend those of previous findings by demonstrating that the reinforcing effects of d-amphetamine vary as a function of the biologically based sensation-seeking personality trait. These results suggest that increased stimulant drug use and abuse among high sensation seekers may be related, in part, to increased sensitivity to the reinforcing effects of stimulants among these individuals. PMID:17011712

  8. Behind the Label "Alcoholic."

    ERIC Educational Resources Information Center

    Wright, Deborah M.

    1989-01-01

    Relates individual's personal story of her childhood influenced by her parent's alcoholism, her own alcoholism as a young adult, and her experiences with counseling. Asks others not to reject her because of the label "alcoholic." (ABL)

  9. Breath alcohol test

    MedlinePlus

    Alcohol test - breath ... There are various brands of breath alcohol tests. Each one uses a different method to test the level of alcohol in the breath. The machine may be electronic or manual. One ...

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

    PubMed

    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

  11. Mortality, causes of death and risk factors for death among primary amphetamine users in the Swedish criminal justice system.

    PubMed

    Ericsson, Emmy; Bradvik, Louise; Hakansson, Anders

    2014-02-01

    This study examined mortality and predictors of death in 1,396 primary amphetamine users (85% males) who were interviewed with the Addiction Severity Index in the Swedish criminal justice system during 2000-2006 and followed through 2008. Forty-nine clients deceased (standardized mortality ratio 4.1 [3.0-5.4]), at least 84% of deaths were violent or drug-related (12% suicides), and Cox regression analysis indicated that death was associated with frequent use of sedatives and less frequent use of amphetamine. No female deaths were observed; death and male gender were associated in binary analysis. Implications for diagnostics and treatment are discussed.

  12. Histone Deacetylase Inhibitors Modulates the Induction and Expression of Amphetamine-induced Behavioral Sensitization Partially Through an Associated Learning of the Environment in Mice

    PubMed Central

    Kalda, Anti; Heidmets, Lenne-Triin; Shen, Hai-ying; Zharkovsky, Alexander; Chen, Jiang-Fan

    2010-01-01

    The behavioral sensitization produced by repeated amphetamine treatment may represent the neural adaptations underlying some of the features of psychosis and addiction in humans. Chromatin modification (specifically histone hyperacetylation) was recently recognized as an important regulator of psychostimulant-induced plasticity. We have investigated the effects of treatment with the histone deacetylase (HDAC) inhibitors butyric acid (BA, 630 mg/kg, i.p) and valproic acid (VPA, 175 mg/kg, i.p.) on the psyhcostimulant locomotor sensitization induced by amphetamine (AMPH, 2.0 mg/kg, i.p.). Neither BA nor VPA had locomotor effects alone, but both significantly potentiated the amphetamine-induced behavioral sensitization in mice. At the molecular level, VPA and amphetamine produced an increase of histone H4 acetylation in the striatum as detected by Western blot analysis, while co-treatment with VPA and AMPH produced an additive effect on histone H4 acetylation. We then administered the HDAC inhibitors after treatment with amphetamine for 8 days to establish locomotor sensitization. We found that repeated administration of VPA or BA for 6 days inhibited the expression of sensitized response following amphetamine challenge. Finally, in a context-specific model we studied the effect of HDAC inhibitors on amphetamine-induced association of the treatment environment (associative learning). We found that VPA and BA enhance the context-specificity of expression of amphetamine sensitization. Thus, HDAC inhibitors differentially modulate the induction and expression of amphetamine-induced effects. Together, these results suggest that dynamic changes in chromatin modification may be an important mechanism underlying amphetamine-induced neuronal plasticity and associative learning. PMID:17477979

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Developmental Exposure to Polychlorinated Biphenyls Reduces Amphetamine Behavioral Sensitization in Long-Evans Rats

    PubMed Central

    Poon, Emily; Monaikul, Supida; Kostyniak, Paul J.; Chi, Lai Har; Schantz, Susan L.; Sable, Helen J. K.

    2013-01-01

    PCBs have long been known to affect dopamine (DA) function in the brain. The current study used an amphetamine behavioral sensitization paradigm in rats developmentally exposed to PCBs. Long-Evans rats were given perinatal exposure to 0, 3, or 6 mg/kg/day PCBs and behavioral sensitization to d-amphetamine (AMPH) was assessed in one adult male and female/litter. Non-exposed (control) males showed increasing locomotor activity to repeated injections of 0.5 mg/kg AMPH, typical of behavioral sensitization. PCB-exposed males showed greater activation to the initial acute AMPH injection, but sensitization occurred later and was blunted relative to controls. Sensitization in control females took longer to develop than in the males, but no exposure-related differences were observed. Analysis of whole brain and serum AMPH content following a final IP injection of 0.5 mg/kg revealed no differences among the exposure groups. Overall, these results indicated developmental PCB-exposure can alter the motor-stimulating effects of repeated AMPH injections. Males developmentally exposed to PCBs appeared to be pre-sensitized to AMPH, but quickly showed behavioral tolerance to the same drug dose. Results also revealed the behavioral effect was not due to exposure-induced alterations in AMPH metabolism following PCB exposure. PMID:23623962

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

    PubMed

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

    2015-12-01

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

  17. Does zinc moderate essential fatty acid and amphetamine treatment of attention-deficit/hyperactivity disorder?

    PubMed

    Arnold, L E; Pinkham, S M; Votolato, N

    2000-01-01

    Zinc is an important co-factor for metabolism relevant to neurotransmitters, fatty acids, prostaglandins, and melatonin, and indirectly affects dopamine metabolism, believed intimately involved in attention-deficit/hyperactivity disorder (ADHD). To explore the relationship of zinc nutrition to essential fatty acid supplement and stimulant effects in treatment of ADHD, we re-analyzed data from an 18-subject double-blind, placebo-controlled crossover treatment comparison of d-amphetamine and Efamol (evening primrose oil, rich in gamma-linolenic acid). Subjects were categorized as zinc-adequate (n = 5), borderline zinc (n = 5), and zinc-deficient (n = 8) by hair, red cell, and urine zinc levels; for each category, placebo-active difference means were calculated on teachers' ratings. Placebo-controlled d-amphetamine response appeared linear with zinc nutrition, but the relationship of Efamol response to zinc appeared U-shaped; Efamol benefit was evident only with borderline zinc. Placebo-controlled effect size (Cohen's d) for both treatments ranged up to 1.5 for borderline zinc and dropped to 0.3-0.7 with mild zinc deficiency. If upheld by prospective research, this post-hoc exploration suggests that zinc nutrition may be important for treatment of ADHD even by pharmacotherapy, and if Efamol benefits ADHD, it likely does so by improving or compensating for borderline zinc nutrition. PMID:10933121

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

    PubMed

    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.

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

    PubMed Central

    Jiao, Dongliang; liu, Yao; Li, Xiaohong; liu, Jinggen; Zhao, Min

    2015-01-01

    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. PMID:25999814

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

    PubMed

    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. PMID:26327309

  1. Endogenous 5-HT outflow from chicken aorta by 5-HT uptake inhibitors and amphetamine derivatives

    PubMed Central

    DELGERMURUN, Dugar; ITO, Shigeo; OHTA, Toshio; YAMAGUCHI, Soichiro; OTSUGURO, Ken-ichi

    2015-01-01

    Chemoreceptor cells aggregating in clusters in the chicken thoracic aorta contain 5-hydroxytryptamine (5-HT) and have voltage-dependent ion channels and nicotinic acetylcholine receptors, which are characteristics typically associated with neurons. The aim of the present study was to investigate the effects of 5-HT uptake inhibitors, fluvoxamine, fluoxetine and clomipramine (CLM), and amphetamine derivatives, p-chloroamphetamine (PCA) and methamphetamine (MET), on endogenous 5-HT outflow from the isolated chick thoracic aorta in vitro. 5-HT was measured by using a HPLC system with electrochemical detection. The amphetamine derivatives and 5-HT uptake inhibitors caused concentration-dependent increases in endogenous 5-HT outflow. PCA was about ten times more effective in eliciting 5-HT outflow than MET. The 5-HT uptake inhibitors examined had similar potency for 5-HT outflow. PCA and CLM increased 5-HT outflow in a temperature-dependent manner. The outflow of 5-HT induced by PCA or 5-HT uptake inhibitors was independent of extracellular Ca2+ concentration. The 5-HT outflow induced by CLM, but not that by PCA, was dependent on the extracellular NaCl concentration. These results suggest that the 5-HT uptake system of 5-HT-containing chemoreceptor cells in the chicken thoracic aorta has characteristics similar to those of 5-HT-containing neurons in the mammalian central nervous system (CNS). PMID:26321443

  2. Divergent activation of ventromedial and ventrolateral dopamine systems in animal models of amphetamine sensitization and schizophrenia.

    PubMed

    Lodge, Daniel J; Grace, Anthony A

    2012-02-01

    Aberrant dopamine-mediated behaviours are a hallmark of a number of psychiatric disorders, including substance use disorders and schizophrenia. It has been demonstrated recently that rodent models of these diseases display enhanced dopamine neuron activity throughout the ventral tegmental area (VTA). It is known, however, that the VTA is not a homogeneous structure, and that the dopamine neuron population provides discrete, topographical innervation of nucleus accumbens subregions. In addition, these ventromedial and ventrolateral dopamine systems are known to subserve complementary but distinct aspects of goal-directed behaviour. Using in-vivo extracellular recordings of identified dopamine neurons in chloral hydrate-anaesthetized rats, we examined the level of dopamine neuron population activity across the mediolateral extent of the VTA following amphetamine sensitization or gestational methylazoxymethanol acetate (MAM) treatment, a verified rodent model of schizophrenia. Here we demonstrate that both models display an augmented medial VTA-ventromedial striatal dopamine system function that correlates with the augmented locomotor response to amphetamine observed in both models. In contrast, only MAM-treated rats exhibit an increase in VTA-ventrolateral striatal dopamine system function. This latter finding is consistent with human imaging studies in schizophrenia patients. In summary, we demonstrate that, although a number of disorders involving a hyperdopaminergic state demonstrate an increase in dopamine neuron population activity, there is divergence in the exact populations of neurons affected. This distinction probably underlies the observed differences in disease symptomatology. PMID:21329556

  3. The Histaminergic Tuberomamillary Nucleus Is Involved in Appetite for Sex, Water and Amphetamine.

    PubMed

    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.

  4. The Histaminergic Tuberomamillary Nucleus Is Involved in Appetite for Sex, Water and Amphetamine

    PubMed Central

    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 24h 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. PMID:26845170

  5. Matrix effect and cross-reactivity of select amphetamine-type substances, designer analogues, and putrefactive amines using the Bio-Quant direct ELISA presumptive assays for amphetamine and methamphetamine.

    PubMed

    Apollonio, Luigino G; Whittall, Ian R; Pianca, Dennis J; Kyd, Jennelle M; Maher, William A

    2007-05-01

    The aim of this study was to evaluate the Bio-Quant Direct ELISA assays for amphetamine and methamphetamine in the routine presumptive screening of biological fluids. Standard concentration curves of the target analytes were assayed to assess sensitivity, and known concentrations of common amphetamine-type substances (ephedrine, pseudoephedrine, phentermine), designer analogues (MDA, MDMA, MDEA, MBDB, PMA, 4-MTA, 2CB), and putrefactive amines (phenylethylamine, putrescine, tryptamine, tyramine) were analyzed to determine cross-reactivity. Results of the standard curve studies show the capacity of both Direct ELISA kits to confidently detect down to 3 ng/mL interday (PBS matrix; CVs 6.3-15.5%). Cross-reactivity relative to that of 50 ng/mL preparations of the target compounds demonstrated that the Direct ELISA kit for amphetamine also detected MDA (282%), PMA (265%), 4-MTA (280%), and phentermine (61%), and the Direct ELISA for methamphetamine also assayed positive for MDMA (73%), MDEA (18%), pseudoephedrine (19%), MBDB (8%), and ephedrine (9%). Matrix studies demonstrated that both ELISA kits could be applied to screening of blood, urine, and saliva to a concentration of 6 ng/mL or lower. In conclusion, the Bio-Quant Direct ELISA kits for amphetamine and methamphetamine are fast and accurate and have demonstrated themselves to be useful tools in routine toxicological testing.

  6. Health risks of alcohol use

    MedlinePlus

    Alcoholism - risks; Alcohol abuse - risks; Alcohol dependence - risks; Risky drinking ... Beer, wine, and liquor all contain alcohol. If you are drinking any of these, you are using alcohol. Your drinking patterns may vary, depending on who you are with ...

  7. Effects of heavy particle irradiation and diet on amphetamine- and lithium chloride-induced taste avoidance learning in rats

    NASA Technical Reports Server (NTRS)

    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.

  8. Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity

    PubMed Central

    Bowyer, John F; Hanig, Joseph P

    2014-01-01

    The adverse effects of amphetamine- (AMPH) and methamphetamine- (METH) induced hyperthermia on vasculature, peripheral organs and peripheral immune system are discussed. Hyperthermia alone does not produce amphetamine-like neurotoxicity but AMPH and METH exposures that do not produce hyperthermia (≥40°C) are minimally neurotoxic. Hyperthermia likely enhances AMPH and METH neurotoxicity directly through disruption of protein function, ion channels and enhanced ROS production. Forebrain neurotoxicity can also be indirectly influenced through the effects of AMPH- and METH- induced hyperthermia on vasculature. The hyperthermia and the hypertension produced by high doses amphetamines are a primary cause of transient breakdowns in the blood-brain barrier (BBB) resulting in concomitant regional neurodegeneration and neuroinflammation in laboratory animals. This BBB breakdown can occur in the amygdala, thalamus, striatum, sensory and motor cortex and hippocampus. Under these conditions, repetitive seizures greatly enhance neurodegeneration in hippocampus, thalamus and amygdala. Even when the BBB is less disrupted, AMPH- or METH- induced hyperthermia effects on brain vasculature may play a role in neurotoxicity. In this case, striatal and cortical vascular function are adversely affected, and even greater ROS, immune and damage responses are seen in the meninges and cortical surface vasculature. Finally, muscle and liver damage and elevated cytokines in blood can result when amphetamines produce hyperthermia. Proteins, from damaged muscle may activate the peripheral immune system and exacerbate liver damage. Liver damage can further increase cytokine levels, immune system activation and increase ammonia levels. These effects could potentially enhance vascular damage and neurotoxicity. PMID:27626044

  9. High-anxiety rats are less sensitive to the rewarding affects of amphetamine on 50kHz USV.

    PubMed

    Lehner, Małgorzata H; Taracha, Ewa; Kaniuga, Ewelina; Wisłowska-Stanek, Aleksandra; Wróbel, Jacek; Sobolewska, Alicja; Turzyńska, Danuta; Skórzewska, Anna; Płaźnik, Adam

    2014-12-15

    This study assessed behaviour, as measured by 50kHz calls related to positive affect, in rats with different fear conditioned response strengths: low-anxiety rats (LR) and high-anxiety rats (HR), after amphetamine injection in a two-injection protocol (TIPS). The results showed that the first dose of amphetamine evoked similar behavioural effects in frequency-modulated (FM) 50kHz calls in the LR and HR groups. The second injection of amphetamine resulted in stronger FM 50kHz calls in LR compared with HR rats. The biochemical data ('ex vivo' analysis) showed that the LR rats had increased basal levels of dopamine in the amygdala, and increased homovanilic acid (HVA), dopamine's main metabolite, in the amygdala and prefrontal cortex compared with HR rats. The 'in vivo' analysis (microdialysis study) showed that the LR rats had increased HVA concentrations in the basolateral amygdala in response to an aversively conditioned context. Research has suggested that differences in dopaminergic system activity in the amygdala and prefrontal cortex may be one of the biological factors that underlie individual differences in response to fear stimuli, which may also affect the rewarding effects of amphetamine.

  10. The impact of D-amphetamine and SCH23390 on behavioral momentum of food seeking and reinstatement in rats.

    PubMed

    Quick, Stacey L; Shahan, Timothy A

    2015-04-01

    Although the environmental determinants of context-specific behavioral persistence have been extensively studied within behavioral momentum theory, little is known about the neurobiological determinants. The present experiment assessed the impact of indirect dopamine agonism with D-amphetamine or dopamine D1 receptor antagonism with SCH23390 on context-specific persistence of behavior. Two groups of rats were trained to make operant responses for equal rates of food delivery in two alternating contexts arranged across sessions. Following baseline, rats received either drug (D-amphetamine or SCH23390) or saline injections before each context. Resistance to extinction and reinstatement in each context were subsequently tested in the absence of drug. Previous exposure to D-amphetamine increased resistance to extinction and reinstatement of behavior, whereas SCH23390 had little impact on resistance to extinction and enhanced reinstatement in the saline context. Quantitative analyses based on behavioral momentum theory suggested that previous treatment with D-amphetamine within a stimulus context may have resulted in a shift to more habitual stimulus-driven behavior that was impacted less by reinforcer omission during subsequent extinction. These results suggest that the persistence of behavior is greater in a context associated with dopamine receptor agonism and that the activity at D1 receptors may differentially modulate extinction and reinstatement performance. These findings may serve as a starting point for future examination and integration of the biological and environmental determinants of behavioral persistence within the framework of behavioral momentum theory.

  11. Amphetamine Withdrawal Differentially Increases the Expression of Organic Cation Transporter 3 and Serotonin Transporter in Limbic Brain Regions

    PubMed Central

    Solanki, Rajeshwari R.; Scholl, Jamie L.; Watt, Michael J.; Renner, Kenneth J.; Forster, Gina L.

    2016-01-01

    Amphetamine withdrawal increases anxiety and stress sensitivity related to blunted ventral hippocampus (vHipp) and enhances the central nucleus of the amygdala (CeA) serotonin responses. Extracellular serotonin levels are regulated by the serotonin transporter (SERT) and organic cation transporter 3 (OCT3), and vHipp OCT3 expression is enhanced during 24 hours of amphetamine withdrawal, while SERT expression is unaltered. Here, we tested whether OCT3 and SERT expression in the CeA is also affected during acute withdrawal to explain opposing regional alterations in limbic serotonergic neurotransmission and if respective changes continued with two weeks of withdrawal. We also determined whether changes in transporter expression were confined to these regions. Male rats received amphetamine or saline for two weeks followed by 24 hours or two weeks of withdrawal, with transporter expression measured using Western immunoblot. OCT3 and SERT expression increased in the CeA at both withdrawal timepoints. In the vHipp, OCT3 expression increased only at 24 hours of withdrawal, with an equivalent pattern seen in the dorsomedial hypothalamus. No changes were evident in any other regions sampled. These regionally specific changes in limbic OCT3 and SERT expression may partially contribute to the serotonergic imbalance and negative affect during amphetamine withdrawal. PMID:27478387

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. Amphetamine-Induced Taste Aversion Learning in Young and Old F-344 Rats Following Exposure to 56Fe Particles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposure to 56Fe particles produces changes in dopaminergic function and in dopamine dependent behaviors, including amphetamine-induced conditioned taste aversion (CTA) learning. Because many of these changes are characteristic of the changes that accompany the aging process, the present study was ...

  14. Integration of neural networks activated by amphetamine in females with different estrogen levels: a functional imaging study in awake rats.

    PubMed

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

    2015-06-01

    Previous studies demonstrate that schizophrenia symptomatology in women is dependent upon estrogen levels. Estrogen has beneficial properties when administered in conjunction with antipsychotics, and estrogen also alters, in rats, dopamine neurotransmission, which is a common target of all antipsychotic medications, suggesting a possible interaction between the two. The aim of the current study was to investigate this possible interaction using functional magnetic resonance imaging in awake, female rats. Amphetamine-sensitized, ovariectomized rats receiving no, chronic low, or phasic high levels of estradiol replacement were used, and changes in blood-oxygen-level-dependent (BOLD) signal were recorded over time in response to an acute amphetamine injection. Increasing levels of estradiol enhanced BOLD activation in pathways previously known to be implicated in schizophrenia symptomatology, such as the mesocorticolimbic, habenular and olfactory pathways, as well as more widespread areas. We propose here the first comprehensive "amphetamine activation map" integrating brain regions where amphetamine-related BOLD activity is influenced by estrogen levels in sensitized female rats. PMID:25827963

  15. Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity

    PubMed Central

    Bowyer, John F; Hanig, Joseph P

    2014-01-01

    The adverse effects of amphetamine- (AMPH) and methamphetamine- (METH) induced hyperthermia on vasculature, peripheral organs and peripheral immune system are discussed. Hyperthermia alone does not produce amphetamine-like neurotoxicity but AMPH and METH exposures that do not produce hyperthermia (≥40°C) are minimally neurotoxic. Hyperthermia likely enhances AMPH and METH neurotoxicity directly through disruption of protein function, ion channels and enhanced ROS production. Forebrain neurotoxicity can also be indirectly influenced through the effects of AMPH- and METH- induced hyperthermia on vasculature. The hyperthermia and the hypertension produced by high doses amphetamines are a primary cause of transient breakdowns in the blood-brain barrier (BBB) resulting in concomitant regional neurodegeneration and neuroinflammation in laboratory animals. This BBB breakdown can occur in the amygdala, thalamus, striatum, sensory and motor cortex and hippocampus. Under these conditions, repetitive seizures greatly enhance neurodegeneration in hippocampus, thalamus and amygdala. Even when the BBB is less disrupted, AMPH- or METH- induced hyperthermia effects on brain vasculature may play a role in neurotoxicity. In this case, striatal and cortical vascular function are adversely affected, and even greater ROS, immune and damage responses are seen in the meninges and cortical surface vasculature. Finally, muscle and liver damage and elevated cytokines in blood can result when amphetamines produce hyperthermia. Proteins, from damaged muscle may activate the peripheral immune system and exacerbate liver damage. Liver damage can further increase cytokine levels, immune system activation and increase ammonia levels. These effects could potentially enhance vascular damage and neurotoxicity.

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  17. The Threat of Hepatitis C as an Influence on Injecting Amphetamine Users' Change towards Non-Injecting

    ERIC Educational Resources Information Center

    Davey, Jeremy; Richards, Naomi; Lang, Cathryne P.; Davies, Amanda

    2006-01-01

    Young injecting drug users are a particularly vulnerable group for Hepatitis C (HCV) infection. One method for minimising the risk of contraction of Hepatitis C for amphetamine users (not widely explored in the research to date) is through encouraging non-injecting routes of administration (NIROA). Self-report data from 150 young injecting…

  18. Rapid Acquisition of Preference in Concurrent Chains: Effects of D-amphetamine on Sensitivity to Reinforcement Delay

    PubMed Central

    T, Wei-Min; Pitts, Raymond C; Hughes, Christine E; McLean, Anthony P; Grace, Randolph C

    2008-01-01

    The purpose of this study was to examine effects of d-amphetamine on choice controlled by reinforcement delay. Eight pigeons responded under a concurrent-chains procedure in which one terminal-link schedule was always fixed-interval 8 s, and the other terminal-link schedule changed from session to session between fixed-interval 4 s and fixed-interval 16 s according to a 31-step pseudorandom binary sequence. After sufficient exposure to these contingencies (at least once through the pseudorandom binary sequence), the pigeons acquired a preference for the shorter reinforcement delay within each session. Estimates of the sensitivity to reinforcement immediacy were similar to those obtained in previous studies. For all pigeons, at least one dose of d-amphetamine attenuated preference and, hence, decreased estimates of sensitivity to reinforcement immediacy; in most cases, this effect occurred without a change in overall response rates. In many cases, the reduced sensitivity to reinforcement delay produced by d-amphetamine resulted primarily from a decrease in the asymptotic level of preference achieved within the session; in some cases, d-amphetamine produced complete indifference. These findings suggest that a reduction in the sensitivity to reinforcement delay may be an important behavioral mechanism of the effects of psychomotor stimulants. PMID:18338676

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

    PubMed

    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.

  20. The impact of D-amphetamine and SCH23390 on behavioral momentum of food seeking and reinstatement in rats.

    PubMed

    Quick, Stacey L; Shahan, Timothy A

    2015-04-01

    Although the environmental determinants of context-specific behavioral persistence have been extensively studied within behavioral momentum theory, little is known about the neurobiological determinants. The present experiment assessed the impact of indirect dopamine agonism with D-amphetamine or dopamine D1 receptor antagonism with SCH23390 on context-specific persistence of behavior. Two groups of rats were trained to make operant responses for equal rates of food delivery in two alternating contexts arranged across sessions. Following baseline, rats received either drug (D-amphetamine or SCH23390) or saline injections before each context. Resistance to extinction and reinstatement in each context were subsequently tested in the absence of drug. Previous exposure to D-amphetamine increased resistance to extinction and reinstatement of behavior, whereas SCH23390 had little impact on resistance to extinction and enhanced reinstatement in the saline context. Quantitative analyses based on behavioral momentum theory suggested that previous treatment with D-amphetamine within a stimulus context may have resulted in a shift to more habitual stimulus-driven behavior that was impacted less by reinforcer omission during subsequent extinction. These results suggest that the persistence of behavior is greater in a context associated with dopamine receptor agonism and that the activity at D1 receptors may differentially modulate extinction and reinstatement performance. These findings may serve as a starting point for future examination and integration of the biological and environmental determinants of behavioral persistence within the framework of behavioral momentum theory. PMID:25485644

  1. Cardiovascular effects of 0.5 milligrams per kilogram oral d-amphetamine and possible attenuation by haloperidol.

    PubMed

    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.

  2. Rapid Acquisition of Preference in Concurrent Chains: Effects of "d"-Amphetamine on Sensitivity to Reinforcement Delay

    ERIC Educational Resources Information Center

    Ta, Wei-Min; Pitts, Raymond C.; Hughes, Christine E.; McLean, Anthony P.; Grace, Randolph C.

    2008-01-01

    The purpose of this study was to examine effects of "d"-amphetamine on choice controlled by reinforcement delay. Eight pigeons responded under a concurrent-chains procedure in which one terminal-link schedule was always fixed- interval 8 s, and the other terminal-link schedule changed from session to session between fixed-interval 4 s and…

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

    ERIC Educational Resources Information Center

    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…

  4. Long-Term Tolerability and Effectiveness of Once-Daily Mixed Amphetamine Salts (Adderall XR) in Children with ADHD

    ERIC Educational Resources Information Center

    McGough, James J.; Biederman, Joseph; Wigal, Sharon B.; Lopez, Frank A.; McCracken, James T.; Spencer, Thomas; Zhang, Yuxin; Tulloch, Simon J.

    2005-01-01

    Objective: To evaluate the long-term tolerability and effectiveness of extended-release mixed amphetamine salts (MAS XR; Adderall XR[R]) in children with attention-deficit/hyperactivity disorder (ADHD). Method: This was a 24-month, multicenter, open-label extension of TWO placebo-controlled studies of MAS XR in children with ADHD aged 6 to 12…

  5. Synergistic activity between the delta-opioid agonist SNC80 and amphetamine occurs via a glutamatergic NMDA-receptor dependent mechanism

    PubMed Central

    Bosse, Kelly E.; Jutkiewicz, Emily M.; Schultz, Kristin N.; Mabrouk, Omar S.; Kennedy, Robert T.; Gnegy, Margaret E.; Traynor, John R.

    2014-01-01

    Glutamate is known to cause the release of dopamine through a Ca2+-sensitive mechanism that involves activation of NMDA ionotropic glutamate receptors. In the current study, we tested the hypothesis that the delta opioid agonist SNC80 acts indirectly, via the glutamatergic system, to enhance both amphetamine-stimulated dopamine efflux from striatal preparations and amphetamine-stimulated locomotor activity. SNC80 increased extracellular glutamate content, which was accompanied by a concurrent decrease in GABA levels. Inhibition of NMDA signaling with the selective antagonist MK801 blocked the enhancement of both amphetamine-induced dopamine efflux and hyperlocomotion observed with SNC80 pretreatment. Addition of exogenous glutamate also potentiated amphetamine-stimulated dopamine efflux in a Mg2+- and MK801-sensitive manner. After removal of Mg2+ to relieve the ion conductance inhibition of NMDA receptors, SNC80 both elicited dopamine release alone and produced a greater enhancement of amphetamine-evoked dopamine efflux. The action of SNC80 to enhance amphetamine-evoked dopamine efflux was mimicked by the GABAB antagonist 2-hydroxysaclofen. These cumulative findings suggest SNC80 modulates amphetamine-stimulated dopamine efflux through an intra-striatal mechanism involving inhibition of GABA transmission leading to the local release of glutamate followed by subsequent activation of NMDA receptors. PMID:24035916

  6. Glucostatic regulation of (+)-(/sup 3/H)amphetamine binding in the hypothalamus: correlation with Na/sup +/, K/sup +/-ATPase activity

    SciTech Connect

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

    1985-09-01

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

  7. Nurses' Attitudes towards Alcoholics.

    ERIC Educational Resources Information Center

    Speer, Rita D.

    Nurses' attitudes toward the alcoholic can have a profound impact on the person suffering from alcoholism. These attitudes can affect the alcoholic's care and even whether the alcoholic chooses to recover. This study investigated attitudes of approximately 68 nurses employed in hospitals, 49 nurses in treatment facilities, 58 nursing students, and…

  8. Internet Alcohol Marketing and Underage Alcohol Use

    PubMed Central

    McClure, Auden C.; Tanski, Susanne E.; Li, Zhigang; Jackson, Kristina; Morgenstern, Matthis; Li, Zhongze; Sargent, James D.

    2016-01-01

    BACKGROUND AND OBJECTIVE Internet alcohol marketing is not well studied despite its prevalence and potential accessibility and attractiveness to youth. The objective was to examine longitudinal associations between self-reported engagement with Internet alcohol marketing and alcohol use transitions in youth. METHODS A US sample of 2012 youths aged 15 to 20 was surveyed in 2011. An Internet alcohol marketing receptivity score was developed, based on number of positive responses to seeing alcohol advertising on the Internet, visiting alcohol brand Web sites, being an online alcohol brand fan, and cued recall of alcohol brand home page images. We assessed the association between baseline marketing receptivity and both ever drinking and binge drinking (≥6 drinks per occasion) at 1-year follow-up with multiple logistic regression, controlling for baseline drinking status, Internet use, sociodemographics, personality characteristics, and peer or parent drinking. RESULTS At baseline, ever-drinking and binge-drinking prevalence was 55% and 27%, respectively. Many (59%) reported seeing Internet alcohol advertising, but few reported going to an alcohol Web site (6%) or being an online fan (3%). Higher Internet use, sensation seeking, having family or peers who drank, and past alcohol use were associated with Internet alcohol marketing receptivity, and a score of 1 or 2 was independently associated with greater adjusted odds of initiating binge drinking (odds ratio 1.77; 95% confidence interval, 1.13–2.78 and odds ratio 2.15; 95% confidence interval, 1.06–4.37 respectively) but not with initiation of ever drinking. CONCLUSIONS Although high levels of engagement with Internet alcohol marketing were uncommon, most underage youths reported seeing it, and we found a prospective association between receptivity to this type of alcohol marketing and future problem drinking, making additional research and ongoing surveillance important. PMID:26738886

  9. Periadolescent amphetamine treatment causes transient cognitive disruptions and long-term changes in hippocampal LTP depending on the endogenous expression of pleiotrophin.

    PubMed

    Gramage, Esther; Del Olmo, Nuria; Fole, Alberto; Martín, Yasmina B; Herradón, Gonzalo

    2013-01-01

    Amphetamine treatment during adolescence causes long-term cognitive deficits in rats. Pleiotrophin (PTN) is a cytokine with important roles in the modulation of synaptic plasticity, whose levels of expression are significantly regulated by amphetamine administration. To test the possibility that the long-term consequences of periadolescent amphetamine treatment cross species and, furthermore, to test the hypothesis that PTN could be one of the factors involved in the adult cognitive deficits observed after periadolescent amphetamine administrations, we comparatively studied the long-term consequences of periadolescent amphetamine treatment (3 mg/kg intraperitoneal, daily during 10 days) in normal wild-type (PTN+/+) and in PTN genetically deficient (PTN-/-) mice. Within the first week after cessation of treatment, significant deficits in the passive avoidance and Y-maze tests were only observed in amphetamine-pretreated PTN-/- mice. However, 13 and 26 days after the last administration, we did not find significant differences in Y-maze between amphetamine- and saline-pretreated PTN-/- mice. In addition, we did not find any genotype- or treatment-related anxiogenic- or depressive-like behaviour in adult mice. Furthermore, we observed a significantly enhanced long-term potentiation (LTP) in CA1 hippocampal slices from saline-pretreated PTN-/- mice compared with saline-pretreated PTN+/+ mice. Interestingly, amphetamine pre-treatment during adolescence significantly enhanced LTP in adult PTN+/+ mice but did not cause any effect in PTN-/- mice, suggesting LTP mechanisms saturation in naïve PTN-/- mice. The data demonstrate that periadolescent amphetamine treatment causes transient cognitive deficits and long-term alterations of hippocampal LTP depending on the endogenous expression of PTN.

  10. Alcohol and bone.

    PubMed

    Mikosch, Peter

    2014-01-01

    Alcohol is widely consumed across the world in different cultural and social settings. Types of alcohol consumption differ between (a) light, only occasional consumption, (b) heavy chronic alcohol consumption, and (c) binge drinking as seen as a new pattern of alcohol consumption among teenagers and young adults. Heavy alcohol consumption is detrimental to many organs and tissues, including bones. Osteoporosis is regularly mentioned as a secondary consequence of alcoholism, and chronic alcohol abuse is established as an independent risk factor for osteoporosis. The review will present the different mechanisms and effects of alcohol intake on bone mass, bone metabolism, and bone strength, including alcoholism-related "life-style factors" such as malnutrition, lack of exercise, and hormonal changes as additional causative factors, which also contribute to the development of osteoporosis due to alcohol abuse. PMID:24477631

  11. [Alcohol and arrhythmias].

    PubMed

    Pfeiffer, D; Jurisch, D; Neef, M; Hagendorff, A

    2016-09-01

    The effects of alcohol on induction of arrhythmias is dose-dependent, independent of preexisting cardiovascular diseases or heart failure and can affect otherwise healthy subjects. While the probability of atrial fibrillation increases with the alcohol dosage, events of sudden cardiac death are less frequent with low and moderate consumption but occur more often in heavy drinkers with alcoholic cardiomyopathy. Men are first affected at higher dosages of alcohol but women can suffer from arrhythmias at lower dosages. Thromboembolisms and ischemic stroke can occur less often at lower dosages of alcohol; however, hemorrhagic stroke and subarachnoid hemorrhage are increased with higher alcohol dosages. Recognizable protective mechanisms of alcohol with respect to cardiovascular diseases only occur with lower amounts of alcohol of less than 10 g per day. Underlying mechanisms explain these controversial effects. Specific therapeutic options for alcohol-related arrhythmias apart from abstinence from alcohol consumption are not known. PMID:27582366

  12. Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors: interactions with amphetamine.

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    Steinkellner, Thomas; Montgomery, Therese R.; Hofmaier, Tina; Kudlacek, Oliver; Yang, Jae-Won; Rickhag, Mattias; Jung, Gangsoo; Lubec, Gert; Gether, Ulrik; Freissmuth, Michael

    2015-01-01

    Serotonergic neurotransmission is terminated by reuptake of extracellular serotonin (5-HT) by the high-affinity serotonin transporter (SERT). Selective 5-HT reuptake inhibitors (SSRIs) such as fluoxetine or escitalopram inhibit SERT and are currently the principal treatment for depression and anxiety disorders. In addition, SERT is a major molecular target for psychostimulants such as cocaine and amphetamines. Amphetamine-induced transport reversal at the closely related dopamine transporter (DAT) has been shown previously to be contingent upon modulation by calmodulin kinase IIα (αCaMKII). Here, we show that not only DAT, but also SERT, is regulated by αCaMKII. Inhibition of αCaMKII activity markedly decreased amphetamine-triggered SERT-mediated substrate efflux in both cells coexpressing SERT and αCaMKII and brain tissue preparations. The interaction between SERT and αCaMKII was verified using biochemical assays and FRET analysis and colocalization of the two molecules was confirmed in primary serotonergic neurons in culture. Moreover, we found that genetic deletion of αCaMKII impaired the locomotor response of mice to 3,4-methylenedioxymethamphetamine (also known as “ecstasy”) and blunted d-fenfluramine-induced prolactin release, substantiating the importance of αCaMKII modulation for amphetamine action at SERT in vivo as well. SERT-mediated substrate uptake was neither affected by inhibition of nor genetic deficiency in αCaMKII. This finding supports the concept that uptake and efflux at monoamine transporters are asymmetric processes that can be targeted separately. Ultimately, this may provide a molecular mechanism for putative drug developments to treat amphetamine addiction. PMID:26019340

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

    PubMed

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

    2015-04-01

    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. PMID:25336209

  16. Alcohol fuels

    SciTech Connect

    Not Available

    1990-07-01

    Ethanol is an alcohol made from grain that can be blended with gasoline to extend petroleum supplies and to increase gasoline octane levels. Congressional proposals to encourage greater use of alternative fuels could increase the demand for ethanol. This report evaluates the growth potential of the ethanol industry to meet future demand increases and the impacts increased production would have on American agriculture and the federal budget. It is found that ethanol production could double or triple in the next eight years, and that American farmers could provide the corn for this production increase. While corn growers would benefit, other agricultural segments would not; soybean producers, for example could suffer for increased corn oil production (an ethanol byproduct) and cattle ranchers would be faced with higher feed costs because of higher corn prices. Poultry farmers might benefit from lower priced feed. Overall, net farm cash income should increase, and consumers would see slightly higher food prices. Federal budget impacts would include a reduction in federal farm program outlays by an annual average of between $930 million (for double current production of ethanol) to $1.421 billion (for triple production) during the eight-year growth period. However, due to an partial tax exemption for ethanol blended fuels, federal fuel tax revenues could decrease by between $442 million and $813 million.

  17. Chronic cerebral effects of alcohol and drug abuse.

    PubMed

    Grant, I; Mohns, L

    1975-01-01

    A minority of alcohol abusers develop severe cerebral dysfunction in the form of Wernicke-Korsakoff syndrome. There is also evidence to suggest that cerebral dysfunction, particularly impaired abstracting ability, occurs in that larger population of heavy drinkers who do not go on to develop the Wernicke-Korsakoff syndrome. There is no consistent evidence that long-term marijuana, hallucinogen, or sedative use causes lasting neuropsychological disturbance. The deficits in abstract thinking reported by some LSD studies are similar to deficits others have reported among alcoholics. Since the LSD studies were not controlled for alcohol use, their interpretation is difficult. It appears that cerebrovascular accidents occur more frequently and at a younger age among amphetamine abusers. There is no reliable information about possible other long-term effects of stimulants on the brain per se (i.e., nonvascular complications). Abuse of intravenous narcotics has been associated with case reports of transverse myelitis and encephalitis. It is not known whether this pathology is a direct or hypersensitivity effect of narcotic drugs, of adulterants, or of infection.

  18. Analytical characterization of four new ortho-methoxybenzylated amphetamine-type designer drugs.

    PubMed

    Westphal, Folker; Girreser, Ulrich; Waldmüller, Delia

    2016-09-01

    In a seizure of German custom authorities four N-(ortho-methoxybenzyl)amines with amphetamine partial structure were obtained as pure compounds: N-(ortho-methoxybenzyl)-3,4-dimethoxyamphetamine (3,4-DMA-NBOMe (1)), N-(ortho-methoxybenzyl)-4-ethylamphetamine (4-EA-NBOMe (2)), N-(ortho-methoxybenzyl)-4-methylmethamphetamine (4-MMA-NBOMe (3)), and N-(ortho-methoxybenzyl)-5-(2-aminopropyl)benzofuran (5-APB-NBOMe (4)). The compounds have been detected in Germany for the first time and no analytical data had been previously published. Mass spectrometric (MS), infrared (IR) spectroscopic, and nuclear magnetic resonance (NMR) spectroscopic data are presented. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Hallucinogens Causing Seizures? A Case Report of the Synthetic Amphetamine 2,5-Dimethoxy-4-Chloroamphetamine

    PubMed Central

    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. PMID:25553227

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

    NASA Astrophysics Data System (ADS)

    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.

  1. 3,4-Methylenedioxy analogues of amphetamine: defining the risks to humans.

    PubMed

    Hegadoren, K M; Baker, G B; Bourin, M

    1999-03-01

    The 3,4-methylenedioxy analogues of amphetamine [MDMA ("Ecstasy", "Adam"), MDA ("Love") and MDE ("Eve")] are recreational drugs that produce feelings of euphoria and energy and a desire to socialize, which go far to explain their current popularity as "rave drugs". In addition to these positive effects, the drugs are relatively inexpensive to purchase and have the reputation of being safe compared to other recreational drugs. Yet there is mounting evidence that these drugs do not deserve this reputation of being safe. This review examines the relevant human and animal literature to delineate the possible risks MDMA, MDA and MDE engender with oral consumption in humans. Following a summary of the behavioral and cognitive effects of MDMA, MDA and MDE, risks will be discussed in terms of toxicity, psychopathology, neurotoxicity, abuse potential and the potential for drug-drug interactions associated with acute and chronic use.

  2. Hallucinogens causing seizures? A case report of the synthetic amphetamine 2,5-dimethoxy-4-chloroamphetamine.

    PubMed

    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. PMID:25553227

  3. Hallucinogens causing seizures? A case report of the synthetic amphetamine 2,5-dimethoxy-4-chloroamphetamine.

    PubMed

    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.

  4. Alcoholic hepatitis.

    PubMed

    Damgaard Sandahl, Thomas

    2014-10-01

    Alcoholic hepatitis (AH) is an acute inflammatory syndrome causing significant morbidity and mortality. The prognosis is strongly dependent on disease severity, as assessed by clinical scoring systems. Reliable epidemiological data as well as knowledge of the clinical course of AH are essential for planning and resource allocation within the health care system. Likewise, individual evaluation of risk is desirable in the clinical handling of patients with AH as it can guide treatment, improve patient information, and serve as strata in clinical trials. The present PhD thesis is based on three studies using a cohort of nearly 2000 patients diagnosed with AH in Denmark from 1999 to 2008 as a cohort, in a population-based study design. The aims of this thesis were as follows. (1) To describe the incidence and short- and long-term mortality, of AH in Denmark (Study I). (2) To validate and compare the ability of the currently available prognostic scores to predict mortality in AH (Study II). (3) To investigate the short- and long-term causes of death of patients with AH (Study III). During the study decade, the annual incidence rate in the Danish population rose from 37 to 46 per 106 for men and from 24 to 34 per 106 for women. Both short- and long-term mortality rose for men and women, and the increase in short-term mortality was attributable to increasing patient age and prevalence of cirrhosis. Our evaluation of the most commonly used prognostic scores for predicting the mortality of patients with AH showed that all scores performed similarly, with Area under the Receiver Operator Characteristics curves giving values between 0.74 and 0.78 for 28-day mortality assessed on admission. Our study on causes of death showed that in the short-term (< 84 days after diagnosis), patients with AH were likely to die from liver-related events and infections. In the long-term (≥ 84 days after diagnosis), those who developed cirrhosis mainly died from liver-related causes, and

  5. Action potentials and amphetamine release antipsychotic drug from dopamine neuron synaptic VMAT vesicles.

    PubMed

    Tucker, Kristal R; Block, Ethan R; Levitan, Edwin S

    2015-08-11

    Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H(+)-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca(2+)-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP(+)), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H(+) countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs.

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

    PubMed

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

    2004-05-01

    Nicotine can improve attentional performance in the rat as assessed by a modified five-choice serial reaction time task (5-CSRTT), but it is not known if the effect is shared with other psychomotor stimulants. This study compared the effects of nicotine, amphetamine, caffeine and methylphenidate on performance in the 5-CSRTT and determined whether presenting stimuli at unpredictable times by using variable inter-trial intervals (ITI) influenced the sensitivity of the task to the drugs. One group of male hooded rats was trained to obtain food reinforcers by nose-poking in response to 1 s light stimuli presented randomly in one of five apertures, with fixed ITI; for a second group of rats, ITI varied randomly (n=12 per group). As observed previously, nicotine (tested in doses of 0.05-0.2 mg/kg) produced dose-related improvements in accuracy, reduced omission errors and response latencies, but increased anticipatory responding. Amphetamine (0.1-0.8 mg/kg) and methylphenidate (2.5-10 mg/kg) increased accuracy and reduced response latency, and decreased anticipatory responding. Caffeine (2.5-20 mg/kg) did not improve performance except at a small dose that decreased omission errors only. Training at different levels of stimulus predictability influenced performance in the undrugged state but had little impact on profiles of responses to the drugs. The findings with methylphenidate support the potential value of the 5-CSRTT for testing drugs that may be useful in the treatment of attention deficit hyperactivity disorder. PMID:15187577

  7. LC-MS/MS screening method for designer amphetamines, tryptamines, and piperazines in serum.

    PubMed

    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%.

  8. Dopamine and conditioned reinforcement. I. Differential effects of amphetamine microinjections into striatal subregions.

    PubMed

    Kelley, A E; Delfs, J M

    1991-01-01

    In the conditioned reinforcement paradigm, animals learn a new instrumental response reinforced solely by conditioned reward (a stimulus that has previously been associated with primary reward). It has been shown that psychostimulants potentiate responding for conditioned reward and there is evidence that the nucleus accumbens is involved in this effect. The present experiments extend this work and examine the roles of various striatal subregions in the enhancement of responding for conditioned reward. In the conditioning phase, hungry rats were trained to associate a light/click stimulus with food delivery, with no levers present in the operant chamber. In the test phase, two levers were present and responding on one provided conditioned reward (presentation of the compound stimulus but no food). During this phase, microinjections of d-amphetamine (0, 0.2, 2.0, 20.0 micrograms/0.5 microliters) were made into seven striatal subregions in separate groups of rats. Injection of amphetamine into the nucleus accumbens elicited a dose-dependent, selective increase in responding for CR. Injections into posterior regions of the striatum had no effect. Significant and selective increases in CR responding were noted after injections into two regions neighboring the nucleus accumbens, the anterior dorsal and the ventromedial striatum, although the magnitude of these effects was considerably less than that following accumbens injections. Injections into ventrolateral regions increased responding in some rats, but this effect was very variable and not selective for the CR lever. These results are interpreted as evidence for functional heterogeneity of the striatum with regard to enhancement of conditioned reinforcement. The findings are discussed in relation to the theory that increased dopaminergic activity in the nucleus accumbens results in amplification of the response to a previously learned reward-related signal.

  9. Dopamine and conditioned reinforcement. I. Differential effects of amphetamine microinjections into striatal subregions.

    PubMed

    Kelley, A E; Delfs, J M

    1991-01-01

    In the conditioned reinforcement paradigm, animals learn a new instrumental response reinforced solely by conditioned reward (a stimulus that has previously been associated with primary reward). It has been shown that psychostimulants potentiate responding for conditioned reward and there is evidence that the nucleus accumbens is involved in this effect. The present experiments extend this work and examine the roles of various striatal subregions in the enhancement of responding for conditioned reward. In the conditioning phase, hungry rats were trained to associate a light/click stimulus with food delivery, with no levers present in the operant chamber. In the test phase, two levers were present and responding on one provided conditioned reward (presentation of the compound stimulus but no food). During this phase, microinjections of d-amphetamine (0, 0.2, 2.0, 20.0 micrograms/0.5 microliters) were made into seven striatal subregions in separate groups of rats. Injection of amphetamine into the nucleus accumbens elicited a dose-dependent, selective increase in responding for CR. Injections into posterior regions of the striatum had no effect. Significant and selective increases in CR responding were noted after injections into two regions neighboring the nucleus accumbens, the anterior dorsal and the ventromedial striatum, although the magnitude of these effects was considerably less than that following accumbens injections. Injections into ventrolateral regions increased responding in some rats, but this effect was very variable and not selective for the CR lever. These results are interpreted as evidence for functional heterogeneity of the striatum with regard to enhancement of conditioned reinforcement. The findings are discussed in relation to the theory that increased dopaminergic activity in the nucleus accumbens results in amplification of the response to a previously learned reward-related signal. PMID:2027920

  10. Microdialysis study of striatal dopamine in MPTP-hemilesioned rats challenged with apomorphine and amphetamine.

    PubMed

    Dombrowski, Patricia Andreia; Carvalho, Milene Cristina; Miyoshi, Edmar; Correia, Diego; Bortolanza, Mariza; Dos Santos, Lucélia Mendes; Wietzikoski, Evellyn Claudia; Eckart, Moritz Thede; Schwarting, Rainer K W; Brandão, Marcus Lira; Da Cunha, Claudio

    2010-12-20

    Motor impairments of Parkinson's disease (PD) appear only after the loss of more than 70% of the DAergic neurons of the substantia nigra pars compacta (SNc). An earlier phase of this disease can be modeled in rats that received a unilateral infusion of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) into the SNc. Though these animals do not present gross motor impairments, they rotate towards the lesioned side when challenged with DAergic drugs, like amphetamine and apomorphine. The present study aimed to test whether these effects occur because the drugs disrupt compensatory mechanisms that keep extracellular levels of dopamine in the striatum (DA(E)) unchanged. This hypothesis was tested by an in vivo microdialysis study in awake rats with two probes implanted in the right and left striatum. Undrugged rats did not present turning behaviour and their basal DA(E) did not differ between the lesioned and sham-lesioned sides. However, after apomorphine treatment, DA(E) decreased in both sides, but to a larger extent in the lesioned side at the time the animals started ipsiversive turning behaviour. After amphetamine challenge, DA(E) increased in both sides, becoming significantly higher in the non-lesioned side at the time the animals started ipsiversive turning behaviour. These results are in agreement with the hypothesis that absence of gross motor impairments in this rat model of early phase PD depends on maintenance of extracellular DA by mechanisms that may be disrupted by events demanding its alteration to higher or lower levels.

  11. Chronic intermittent toluene inhalation in adolescent rats alters behavioural responses to amphetamine and MK801.

    PubMed

    Duncan, Jhodie Rubina; Gibbs, Sarah Jane; Lawrence, Andrew John

    2014-03-01

    Abuse of toluene-containing inhalants is common during adolescence, with ongoing chronic misuse associated with adverse outcomes and increased risk for addictive behaviours in adulthood. However, the mechanisms mediating the adaptive processes related to these outcomes are not well defined. To model human abuse patterns we exposed male adolescent Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (CIT, 10,000 ppm) or air (control) for 1h/day, three times/week for 3 weeks. The effects of CIT on behaviour and recovery were monitored. Locomotor activity was recorded following two consecutive injections of amphetamine (1mg/kg, i.p.) 72 and 96 h after the last exposure. This was followed with injection of the NMDA receptor antagonist MK801 (0.5mg/kg, i.p.) 20 days after the last exposure. CIT resulted in a significant and persistent retardation in weight gain during the exposure period and abstinence (p<0.05). Repeated exposure resulted in tolerance to the onset of toluene-induced behaviours and recovery latency. There was a reduction in the acute stimulant effects of amphetamine in CIT-exposed animals and an increase in the magnitude of locomotor activity (p<0.0125) following a subsequent exposure when compared to the responses observed in controls; this was associated with altered locomotor responses to MK801. Repeated exposure to CIT during adolescence alters parameters of growth, as measured by body weight, and leads to tolerance, indicating that increasing concentrations of the compound may be needed to reach the same behavioural state. Toluene during this period also alters responses to a psychostimulant which may be related to long-term glutamatergic dysfunction.

  12. Action potentials and amphetamine release antipsychotic drug from dopamine neuron synaptic VMAT vesicles

    PubMed Central

    Tucker, Kristal R.; Block, Ethan R.; Levitan, Edwin S.

    2015-01-01

    Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H+-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca2+-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP+), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H+ countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs. PMID:26216995

  13. Correlation between drugs of abuse and alcohol by hair analysis: parents at risk for having children with fetal alcohol spectrum disorder.

    PubMed

    Kulaga, Vivian; Shor, Sarit; Koren, Gideon

    2010-01-01

    The fatty acid ethyl esters (FAEEs) hair test, a biomarker of excessive alcohol exposure, has demonstrated its potential for use in fetal alcohol spectrum disorder (FASD) diagnosis. FASD may be compounded by polydrug exposure. Our objective was to determine the likelihood of positive FAEE test among parents testing positive for other drugs of abuse. Samples submitted for FAEE hair analysis by Children's Aid Societies between October 2005 and May 2007, also concurrently tested for cocaine, cannabinoids, opiates, methamphetamine, amphetamine, benzodiazepines, methadone, and/or oxycodone, were included in our analysis. Subjects consisted of parents suspected of using excessive amounts of alcohol. Parents testing positive for drugs of abuse had a significantly increased risk for testing positive for high FAEE. Mothers testing positive for heavy chronic alcohol use were found to have a threefold increased risk of testing positive for cocaine (odds ratio=3.26, 1.1-9.7). Our results suggest that parents abusing stimulants are at risk of high alcohol exposure, which put their unborn children at risk for FASD. PMID:20580184

  14. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes.

    PubMed

    Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne; Rasmussen, Søren; Tybjaerg-Hansen, Anne; Grønbaek, Morten

    2008-06-01

    Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B.1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B.1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men with the ADH1B.1/1 genotype compared to men with the ADH1B.1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C.1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B.2/2 genotype, compared with men with the ADH1C.1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1B.1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

  15. Perillyl Alcohol (Monoterpene Alcohol), Limonene.

    PubMed

    Shojaei, Shahla; Kiumarsi, Amir; Moghadam, Adel Rezaei; Alizadeh, Javad; Marzban, Hassan; Ghavami, Saeid

    2014-01-01

    Natural products have a long history of use in traditional medicines and their activities against different diseases have been the focus of many basic and clinical researches in past few decades. The essential oils, volatile liquid containing aroma compound from plants, are known as active ingredients in the herbal medicine. Perillyl alcohol (POH) is usually available through dietary sources and is being explored for its cancer chemoprevention, tumor growth suppression, and regression. Citrus peels are the waste product of juice manufacturing industries and have been considered as a critical problem for environmental green ecology policies for years. One of the most well-known approaches to overcome this problem is transformation of these monoterpene by the use of specific strains of bacteria or yeasts. Limonene (1-methyl-4-isopropyl-cyclohexene) is a monoterpene, as other monoterpenes consists of two isoprene units, that comprises more than 90% of citrus essential oil and it exists in many fruits and vegetables. Although, the anticancer activity of d-limonene has identified nearly two decades ago, it has recently attracted much more attention in translational medicine. In this chapter, we will overview the anticancer effects of POH and d-limonene. Later, we will address the pharmacokinetics of these compounds, highlight the signaling pathways which are targeted by these proteins, review the clinical trials which have been done for these compounds in different cancer models, and finally discuss the future directions of the research in this field that might be more applicable in future cancer therapy strategies.

  16. Perillyl Alcohol (Monoterpene Alcohol), Limonene.

    PubMed

    Shojaei, Shahla; Kiumarsi, Amir; Moghadam, Adel Rezaei; Alizadeh, Javad; Marzban, Hassan; Ghavami, Saeid

    2014-01-01

    Natural products have a long history of use in traditional medicines and their activities against different diseases have been the focus of many basic and clinical researches in past few decades. The essential oils, volatile liquid containing aroma compound from plants, are known as active ingredients in the herbal medicine. Perillyl alcohol (POH) is usually available through dietary sources and is being explored for its cancer chemoprevention, tumor growth suppression, and regression. Citrus peels are the waste product of juice manufacturing industries and have been considered as a critical problem for environmental green ecology policies for years. One of the most well-known approaches to overcome this problem is transformation of these monoterpene by the use of specific strains of bacteria or yeasts. Limonene (1-methyl-4-isopropyl-cyclohexene) is a monoterpene, as other monoterpenes consists of two isoprene units, that comprises more than 90% of citrus essential oil and it exists in many fruits and vegetables. Although, the anticancer activity of d-limonene has identified nearly two decades ago, it has recently attracted much more attention in translational medicine. In this chapter, we will overview the anticancer effects of POH and d-limonene. Later, we will address the pharmacokinetics of these compounds, highlight the signaling pathways which are targeted by these proteins, review the clinical trials which have been done for these compounds in different cancer models, and finally discuss the future directions of the research in this field that might be more applicable in future cancer therapy strategies. PMID:27102697

  17. Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry.

    PubMed

    Meyer, Markus R; Wilhelm, Jens; Peters, Frank T; Maurer, Hans H

    2010-06-01

    In recent years, a new class of designer drugs has appeared on the drugs of abuse market in many countries, namely, the so-called beta-keto (bk) designer drugs such as mephedrone (bk-4-methylmethamphetamine), butylone (bk-MBDB), and methylone (bk-MDMA). The aim of the present study was to identify the metabolites of mephedrone in rat and human urine using GC-MS techniques and to include mephedrone, butylone, and methylone within the authors' systematic toxicological analysis (STA) procedure. Six phase I metabolites of mephedrone were detected in rat urine and seven in human urine suggesting the following metabolic steps: N-demethylation to the primary amine, reduction of the keto moiety to the respective alcohol, and oxidation of the tolyl moiety to the corresponding alcohols and carboxylic acid. The STA procedure allowed the detection of mephedrone, butylone, methylone, and their metabolites in urine of rats treated with doses corresponding to those reported for abuse of amphetamines. Besides macro-based data evaluation, an automated evaluation using the automated mass spectral deconvolution and identification system was performed. Mephedrone and butylone could be detected also in human urine samples submitted for drug testing. Assuming similar kinetics in humans, the described STA procedure should be suitable for proof of an intake of the bk-designer drugs in human urine.

  18. Neurologic effects of alcoholism.

    PubMed Central

    Diamond, I; Messing, R O

    1994-01-01

    Alcoholism, a worldwide disorder, is the cause of a variety of neurologic disorders. In this article we discuss the cellular pathophysiology of ethanol addition and abuse as well as evidence supporting and refuting the role of inheritance in alcoholism. A genetic marker for alcoholism has not been identified, but neurophysiologic studies may be promising. Some neurologic disorders related to longterm alcoholism are due predominantly to inadequate nutrition (the thiamine deficiency that causes Wernicke's encephalopathy), but others appear to involve the neurotoxicity of ethanol on brain (alcohol withdrawal syndrome and dementia) and peripheral nerves (alcoholic neuropathy and myopathy). Images PMID:7975567

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

    PubMed Central

    Der-Avakian, Andre; Markou, Athina

    2014-01-01

    Psychostimulant withdrawal leads to depressive symptoms, such as anhedonia and social dysfunction. We determined the effects of withdrawal from chronic exposure to nicotine (9 mg/kg/day salt, 28 days) or amphetamine (10 mg/kg/day salt, 7 days) on the motivated response for a sucrose reward and on social interaction in rats. Both nicotine and amphetamine exposure increased the motivated response for sucrose. However, only spontaneous amphetamine withdrawal led to an immediate and persistent decrease in motivated behavior, which was not correlated with body weight loss. Social interaction was not affected during withdrawal from either drug. These results indicate that withdrawal from chronic amphetamine exposure leads to an immediate and enduring anhedonic state. PMID:20571366

  20. Stereoisomeric identification of norephedrine derived from methamphetamine or amphetamine: urinalysis results of 33 methamphetamine abusers and 1 amphetamine abuser in Japan.

    PubMed

    Nagai, Toshiaki; Kido, Masahito; Maeda, Junko; Matsushima, Kazumi; Okazaki, Toshio; Kurosu, Akira; Hitosugi, Masahito; Tokudome, Shougo

    2007-06-01

    Stereoisomeric identification of norephedrine (NE) derived from methamphetamine (MA) or amphetamine (AM) was investigated by SIM-GC/MS assay using the urine of 33 MA abusers and 1 AM abuser. The assay simultaneously identified TFA-derivatized MA and AM metabolites, including AM, p-hydroxyl-MA (p-HMA), and p-hydroxyl-AM (p-HAM). The analysis lasted approximately 43 min, with a signal-to-noise ratio of >or=3 and a detection limit of 50 ng/mL. Among 12 urine samples from different subjects, only the S (+) form of MA and its metabolites (AM, p-HMA, p-HAM) was detected, however, a (1R,2S)-(-)-NE stereoisomer was also identified. Among the urine samples of two subjects, only the R (-) form of MA and its metabolites (AM, p-HMA, p-HAM) was detected, while NE was not detected. Following urinalysis of urine obtained from 19 MA abusers and 1 AM abuser, only the (1R,2S)-(-)-NE stereoisomer was identified, while unmetabolized MA, AM, and their metabolites (p-HMA, p-HAM), showed stereoselective metabolism. Although (1R,2S)-(-)-ephedrine (EP) alone was found in the urine of 1 (S)-(+)-MA user and 1 (S)-(+)- and (R)-(-)-MA user among 33 MA users, it was not present in the urine of the remaining 31 subjects. Therefore, (1R,2S)-(-)-NE was likely not of (1R,2S)-(-)-EP origin and was most likely from (S)-(+)-AM of the MA metabolite. The production ratio of (1R,2S)-(-)-NE to (S)-(+)-AM ranged from 0.01 to 0.25 in MA abusers and was 0.12 in AM abusers.