BEHAVIORAL AND PHARMACOLOGICAL ANTECEDENTS OF DRUG ABUSE

先前的行为和药物经验可以显著改变 滥用药物的行为影响。在许多情况下，这些先行条件 条件可以使药物的效果发生质的变化，例如 可卡因、安非他明、氯氮卓酮和吗啡，结果是 这些药物产生的效果与通常发现的相反。这个 对这些未被滥用的药物的影响似乎不像 可延展性。由于目前尚不清楚的原因，以前的历史可能 有助于最初的吸毒经验，这可能会为 随后使用和最终的药物滥用。这篇文章中概述的研究 提案的重点是对先行行为和 药理条件：i)改变行为效应 可卡因和咪达唑仑；二)改变这些药物被 自我管理；以及三)修改主观或歧视性 这些药物的刺激作用。行为变量将是 检查包括对事件类型、响应类和 并发环境条件的上下文。药理作用 变量包括以前使用其他药物的经验。其他内容 研究将确定多巴胺和/或5-羟色胺的变化是否会 药物中的中枢受体或转运蛋白的平行修饰 由先行变量产生的影响，实际上可能会中介一些 这些影响。这项提案中概述的研究将产生一个 更好地了解促进或阻碍 个人滥用药物和意志的脆弱性或倾向 提供对行为和药理学的更多洞察 导致这些改变效果的机制。这类研究 对于澄清药物滥用的原因也可能变得重要，因为 以及实施有效的治疗和预防战略。

Prior behavioral and pharmacological experience can markedly alter the behavioral effects of abused drugs. In many instances, these antecedent conditions can produce qualitative changes in the effect of drugs such as cocaine, amphetamine, chlordiazepoxide and morphine, with the result that these drugs produce effects that are opposite those normally found. The effects on these drugs that are not abused do not appear to be as malleable. For reasons that are presently unclear, prior history may contribute to the initial drug experience which may provide the basis for subsequent use and eventual substance abuse. The studies outlined in this proposal focus on an experimental evaluation of antecedent behavioral and pharmacological conditions that: i) alter the behavioral effects of cocaine and midazolam; ii) change the likelihood that these drugs will be self-administered; and iii) modify the subjective or discriminative stimulus effects of these drugs. Behavioral variables that will be examined include an analysis of the type of event, response class and contextual of concurrent environmental conditions. Pharmacological variables include previous experience with other drugs. Additional studies will determine whether changes in dopamine and/or serotonin to central receptor or transporter sites parallel modifications in drug effects produced by antecedent variables and might, in fact, mediate some of those effects. The studies outlined in this proposal will yield a better understanding of antecedent variables that enhance or impede an individual's vulnerability or predisposition to abuse drugs and will provide additional insight into the behavioral and pharmacological mechanisms contributing to those altered effects. Studies of this type may also become important for clarifying the etiology of drug abuse, as well as for implementing effective treatment and prevention strategies.