BEHAVIORAL AND PHARMACOLOGICAL ANTECEDENTS OF DRUG ABUSE

先前的行为和药理学经验可以显著改变 滥用药物的行为影响。 在许多情况下，这些先行词 条件可以产生药物效果的质的变化， 可卡因、安非他明、利和吗啡，结果， 这些药物产生的效果与通常发现的效果相反。 对这些药物的影响，没有滥用似乎并不像 可塑的 由于目前尚不清楚的原因，先前的历史可能 有助于最初的药物经验，这可能为 随后使用和最终滥用药物。 本文中概述的研究 建议侧重于对先前行为和 药理学条件：i）改变的行为效果 可卡因和咪达唑仑; ii）改变这些药物被 自我管理;和iii）修改主观或歧视性 这些药物的刺激作用。 行为变量， 检查包括分析事件的类型，响应类和 同时发生的环境条件。 药理 变量包括以前使用其他药物的经验。 额外 研究将确定多巴胺和/或5-羟色胺的变化是否 药物中的中心受体或转运体位点的平行修饰 影响所产生的先行变量，并可能，事实上，调解一些 这些影响。 本提案中概述的研究将产生一个 更好地理解促进或阻碍 个人滥用药物脆弱性或倾向和意愿 提供了更多的行为和药理学方面的见解， 导致这些改变的机制。 此类研究 也可能成为重要的澄清药物滥用的病因，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.