MODULATION OF ALCOHOL REINFORCEMENT

这个项目直接涉及酒精寻觅行为背后的学习和动机过程。长期目标是提高我们对行为和神经生物学过程的理解，这些过程有助于酒精中毒的病因、维持、消除和复发。一般的实验策略包括研究乙醇在口服自我管理和使用动物的位置条件作用任务中的激励作用。将特别强调从环境刺激和接触乙醇的奖励或厌恶效应之间的预测关系所产生的学习。这项研究的中心组织假设是，酒精预测刺激对酒精的激励作用有直接影响，并且它们重要地参与激励或指导酒精寻求行为，包括在灭绝或禁欲后复发的现象。一组拟议的实验将在大鼠和小鼠的有信号的自我给药过程中检验酒精预测刺激对条件性高热和压抑的影响。感兴趣的变量包括：蔗糖浓度、CS-乙醇重叠、乙醇进入时间和条件性强化。第二组研究将确定酒精预测刺激对大鼠和小鼠条件性位置偏爱和厌恶的影响。感兴趣的变量包括：剂量、试验次数、CS-乙醇间隔、基因和给药途径。最后一系列实验将研究酒精预测刺激在消退、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S激励效应的明显物种差异，以及乙醇预测刺激在同一物种内可以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。该项目将有助于将未来的研究重点放在寻求酒精行为的神经生物学机制上，帮助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。这些研究可能被证明在评估旨在减少酒精渴求的假定药物疗法以及设计减少酒精寻求行为的行为干预方面特别有用。

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.