Determinants of transition states in MDMA self-administration

MDMA 自我给药过渡态的决定因素

• 批准号: 8387029
• 负责人: MICHAEL A. TAFFE
• 金额: $ 37.68万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8387029
• 关键词: Acute; Address; Age; Amphetamines; Animal Experimentation; Anxiety; Attenuated; Attitude; Behavioral; Body Temperature; Brain; Cercopithecidae; Chronic; Clinical; Cocaine; Cognitive; Data; Dependence; Development; Dose; Drug abuse; Emergency Situation; Epidemiology; Etiology; Exercise; Exhibits; Exposure to; Future; Goals; Heroin; High Prevalence; Human; Hyperthermia; Ice; Individual; Intervention; Intravenous; Literature; Maintenance; Medical; Methamphetamine; Minority; Modeling; Monitor; Motor Activity; Neuraxis; Perception; Performance; Pharmaceutical Preparations; Pharmacotherapy; Phase I Clinical Trials; Physiologic Thermoregulation; Physiological; Prevalence; Property; Psychotherapy; Rattus; Regimen; Reporting; Risk; Rodent; Rodent Model; Role; Route; Running; Safety; Schedule; Seizures; Self Administration; Serotonin; Serotonin Agonists; Signal Transduction; Students; Surveys; Symptoms; Techniques; Temperature; Testing; Time; Training; Work; base; clinically significant; cohort; depressive symptoms; design; disturbance in affect; ecstasy; ecstasy abuse; experience; innovation; interest; neurochemistry; neurotoxicity; news; novel therapeutics; pre-clinical research; preclinical study; public health relevance; recreational drug use; reinforcer; research study; young adult

DESCRIPTION (provided by applicant): Epidemiological reports show that (1)3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") continues to be used by large fractions of young adults. Studies have further suggested that up to 40 percent of users become at least temporarily dependent on MDMA, experienced users abuse an array of other substances and may abuse MDMA several times per week or even daily. It is also known that some Ecstasy users exhibit lasting cognitive and mood alterations, even years after discontinuing Ecstasy use. Nevertheless, in comparison with structurally related drugs such as amphetamine and methamphetamine minimal animal research has been devoted to understanding the determinants of repeated MDMA self-administration. Initial work has shown that MDMA appears to be a weak reinforcer compared with other psychomotor stimulants, thus additional study of factors which create a transition to frequent or compulsive MDMA use is needed. The hypothesis that differences in the self administration of MDMA are related to the increased serotonergic agonist properties of MDMA is supported by prior observations that drugs which increase serotonergic tone may decrease self- administration of psychomotor stimulants. Such work will not only contribute to understanding the development of MDMA/Ecstasy abuse but may generalize to understanding factors which influence which of a minority of individuals exposed to other psychomotor stimulants will eventually transition to dependence. The proposed studies will use rat intravenous self-administration models to test factors which may underlie a transition from casual to compulsive Ecstasy use. The experiments will first examine methodological variables such as training dose, route of administration and duration of access session that have not been systematically addressed for MDMA self-administration. Additional studies will examine situational factors intended to model the human user milieu (such as high ambient temperature and hyperthermia, running wheel activity and exposure to a serotonin-depleting high dose regimen of MDMA) which may facilitate a transition to dependence.

描述（由申请人提供）：流行病学报告显示(1)3,4-亚甲基二氧基甲基苯丙胺（MDMA，“摇头丸”）继续被大部分年轻人使用。研究进一步表明，高达40%的使用者至少暂时依赖MDMA，有经验的使用者滥用一系列其他物质，可能每周甚至每天滥用MDMA几次。我们也知道，一些摇头丸使用者表现出持久的认知和情绪变化，甚至在停止使用摇头丸数年后。然而，与结构相关的药物如安非他明和甲基苯丙胺相比，很少有动物研究致力于了解MDMA反复自我给药的决定因素。初步研究表明，与其他精神运动兴奋剂相比，MDMA似乎是一种弱强化剂，因此需要进一步研究导致频繁或强迫性使用MDMA的因素。MDMA自我给药的差异与MDMA的5 -羟色胺能激动剂特性的增加有关的假设得到了先前观察的支持，即增加5 -羟色胺能张力的药物可能会减少精神运动兴奋剂的自我给药。这项工作不仅有助于了解MDMA/摇头丸滥用的发展，而且可以推广到了解影响少数暴露于其他精神运动兴奋剂的个体最终转变为依赖的因素。拟议的研究将使用大鼠静脉内自我给药模型来测试可能从偶然到强迫性使用摇头丸转变的因素。实验将首先检查方法上的变量，如训练剂量、给药途径和接触时间，这些变量尚未系统地用于MDMA自我给药。另外的研究将检查旨在模拟人类使用者环境的情景因素（如高环境温度和热疗，跑步轮活动和暴露于消耗5 -羟色胺的高剂量MDMA方案），这些因素可能有助于过渡到依赖。