Cue-Reactivity and Alcohol Self-Dosing

申请人摘要： 这项拟议的研究的目标是开发一个“线索-反应”模型。 结合经典条件反射和操作性条件反射 程序。反复与环境刺激相关的环境刺激 吸毒和酗酒会引起生理和主观的药物相关效应 在滥用药物和酒精的人类身上。对药物相关刺激的反应性 (即，线索)被认为是经典条件作用过程的函数 并可能在强迫性酒精的发展中发挥重要作用 饮酒和禁欲一段时间后复发的倾向。一种新的 我们实验室一直在开发线索反应性的动物模型。 在演示期间可靠地增加了哪些行为星座 指先于环境刺激(例如，光和音调)的序列 有机会饮用酒精、食物或首选的非酒精饮料 饮料。这些与提示相关的行为包括时间敏感的模式 习得的工具性反应和一般活动，以及自然主义 行为。拟议的实验将系统地检查 对酒精相关线索的反应性、寻酒行为与行为的关系 自治。第一系列研究将评估 提示相关行为对事件的大小变化很敏感 增强剂(即酒精浓度)和所需工作量 (即杠杆反应的数量)以获得酒精。这些研究还将 确定出现的行为类型是否存在差异 重复的药物线索配对以及不同的酒精浓度和 回应“成本”。第二系列研究将评估 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这些相互作用 与环境酒精相关的线索和由 酒精本身对恢复和维持自我管理和 与提示相关的行为。急性“引爆”剂量的酒精或环境提示 将在酒精可供使用的条件下提交 自我管理或被扣留(即禁欲)。这项研究将 确定与线索相关的行为是否可靠地预测酒精 自我管理和恢复吸毒(即旧病复发) 禁欲。这项研究还将提供关于 药物相关线索条件性反应背后的行为过程 在动物身上，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.