MODULATION OF ALCOHOL REINFORCEMENT

这个项目直接关注酒精寻求行为背后的学习和动机过程。长期目标是提高我们对酒精中毒的病因、维持、消除和复发的行为和神经生物学过程的理解。一般的实验策略包括研究乙醇在口服自我给药和场所条件反射任务中的激励效应。将特别强调从环境刺激和暴露于乙醇的奖励或厌恶效应之间的预测关系中得出的学习结果。本研究的中心组织假设是，乙醇预测刺激对乙醇的动机效应有直接影响，并且它们在激励或指导酒精寻求行为中起重要作用，包括在消失或戒断后复发的现象。一组拟议的实验将在大鼠和小鼠的信号自我给药过程中检验乙醇预测刺激对条件热疗和barpressing的影响。感兴趣的变量包括：蔗糖浓度，cs -乙醇重叠，乙醇接触持续时间和条件强化。第二组研究将确定乙醇预测刺激对大鼠和小鼠的条件位置偏好和厌恶的影响。感兴趣的变量包括：剂量、试验次数、cs -乙醇间隔、基因型和给药途径。最后的一系列实验将研究乙醇预测刺激在消退、复发和预防复发中的作用。除了提高我们对乙醇预测刺激的理解外，这些研究还将揭示乙醇激励效应的明显物种差异，以及乙醇预测刺激在同一物种中可能获得相反的激励效应的发现。更好地理解这些问题对于使用这些动物模型来研究酒精中毒的神经生物学和遗传学贡献至关重要。该项目将有助于未来研究酒精寻求行为的神经生物学机制，有助于开发有益的酒精滥用治疗方法，并有助于确定有效的复发预防策略。这些研究在评估旨在减少酒精渴望的假定药物治疗和设计减少酒精寻求行为的行为干预方面可能特别有用。

This project is directly concerned with the learning and motivational processes underlying ethanol-seeking behavior. The long-term goal is to improve our understanding of the behavioral and neurobiological process that contribute to the etiology, maintenance, elimination and relapse of alcoholism. The general experimental strategy involves study of ethanol's motivational effects in oral self-administration and place conditioning tasks using animals. Special emphasis will be placed on the learning that results from the predictive relationship between environmental stimuli and exposure to ethanol rewarding or aversive effects. The central organizing hypothesis of this research is that ethanol-predictive stimuli have a direct impact on ethanol's motivational effects and that they are importantly involved in motivating or directing ethanol-seeking behavior, including the phenomenon of relapse after extinction or abstinence. One set of proposed experiments will examine effects of ethanol-predictive stimuli on conditioned hyperthermia and barpressing in a signaled self-administration procedure using rats and mice. Variables of interest include: Sucrose concentration, CS-ethanol overlap, ethanol access duration and conditioned reinforcement. The second set of studies will determine effects of ethanol-predictive stimuli on conditioned place preference and aversion in rats and mice. Variables of interest include: dose, number of trials, CS-ethanol interval, genotype, and route of administration. The final series of experiments will study the role of ethanol-predictive stimuli in extinction, relapse and relapse prevention. In addition to improving our understanding of ethanol-predictive stimuli, these studies will shed new light on apparent species differences in ethanol s motivational effects, and on findings that ethanol-predictive stimuli can acquire opposing motivational effects within the same species. A better understanding of these issues is essential for using these animal models to study neurobiological and genetic contributions to alcoholism. This project should help focus future research on the neurobiological mechanisms of ethanol-seeking behavior, aid in the development of beneficial treatments for alcohol abuse, and facilitate identification of effective relapse prevention strategies. These studies could prove to be especially useful in the evaluation of putative pharmacotherapies intended to reduce alcohol craving and in the design of behavioral interventions to decrease ethanol-seeking behavior.