Cue-Reactivity and Alcohol Self-Dosing

申请人摘要： 本研究的目标是建立一个线索反应模型 运用经典条件反射和操作性条件反射的结合 程序.环境刺激反复与 药物和酒精的使用引起生理和主观药物相关的影响 在滥用药物和酒精的人身上。对药物相关刺激的反应性 (i.e.,线索）被认为是经典条件反射过程的函数 可能在强迫性酒精的发展中起着重要作用 饮酒和戒酒后复发的倾向。一个新 提示反应的动物模型已经在我们的实验室开发， 在呈现过程中， 一系列环境刺激（例如，灯光和音调）， 消费酒精、食物或首选非酒精饮料的机会 饮料。这些线索相关的行为包括时间敏感的模式， 学习工具反应和一般活动，以及自然主义 行为。拟议的实验将系统地研究 对酒精相关线索的反应性，酒精寻求和 自我管理。第一系列研究将评估是否 线索相关行为对信息量的变化很敏感， 过滤器（即，酒精浓度）和所需的工作量 (i.e.,杠杆响应的数量）以获得酒精。这些研究还将 确定是否有不同类型的行为出现与 重复的药物提示配对和酒精浓度范围， 回应“成本”。第二个系列的研究将评估的影响， 酒精自我给药的戒酒时间和对酒精的反应性 与酒精有关的线索第三系列研究将评估 环境酒精相关线索和内部线索之间的联系， 酒精本身对恢复和维持自我管理， 线索相关行为酒精或环境线索的急性“引发”剂量 将在酒精可用于 自我给药或抑制（即，禁欲）。这项研究将 确定线索相关行为是否可靠地预测酒精 自我给药和恢复服药（即，复发）期间 禁欲这项研究还将提供重要信息， 对药物相关线索的条件反应背后的行为过程 这可能与人类的线索反应和吸毒有关。

APPLICANT'S ABSTRACT: The goal of the proposed research is to develop a model of 'cue-reactivity' using a combination of classical conditioning and operant conditioning procedures. Environmental stimuli that have been repeatedly associated with drug and alcohol use elicit physiological and subjective drug-related effects in humans that abuse drugs and alcohol. Reactivity to drug-related stimuli (i.e., cues) is believed to be a function of classical conditioning processes and may play an important role in the development of compulsive alcohol drinking and in the propensity to relapse after periods of abstinence. A new animal model of cue reactivity has been under development in our laboratory in which a constellation of behaviors are reliably increased during presentation of a sequence of environmental stimuli (e.g., lights and tones) that precede the opportunity to consume alcohol, food or a preferred non-alcoholic beverage. These cue-related behaviors include time sensitive patterns of learned instrumental responses and general activity, as well as naturalistic behaviors. The proposed experiments will systematically examine the relationship between reactivity to alcohol-related cues, alcohol-seeking and self- administration. The first series of studies will evaluate whether cue-related behaviors are sensitive to the changes in the magnitude of the reinforcer (i.e., alcohol concentration) and amount of work effort required (i.e., number of lever responses) to obtain alcohol. These studies will also determine if there are differences in the type of behaviors that emerge with repeated drug-cue pairings and across a range of alcohol concentrations and response 'costs'. A second series of studies will evaluate the influence of length of abstinence on alcohol self- administration and reactivity to alcohol-related cues. A third series of studies will evaluate the interactions between environmental alcohol-related cues and the internal cues produced by alcohol itself on the reinstatement and maintenance of self-administration and cue-related behaviors. Acute 'priming' doses of alcohol or environmental cues will be presented under conditions in which alcohol is available for self-administration or withheld (i.e., abstinence). This research will determine whether cue-related behaviors reliably predict alcohol self-administration and reinstatement of drug-taking (i.e., relapse) during abstinence. This research will additionally provide important information on the behavioral processes underlying conditioned responses to drug-related cues in animals which may be relevant to cue-reactivity and drug-taking in humans.