OPIOID PEPTIDES AND ALCOHOL REINFORCEMENT

这项研究计划解决了酒精诱导的假设 内源性阿片系统的激活是一种神经生物学 促进酒精强化和高酒精度的机制 喝酒。这项提案的目标是确定阿片类药物是否 多肽作为口服酒精自身的神经底物 给药和阐明阿片肽之间的关系， 腹侧被盖区和核团中的多巴胺和GABA 伏隔核(ACB)，大脑中与酒精密切相关的区域 增援。为实现这些目标，将实现以下具体目标 被追查： L。确定选择性阿片类药物是否局部特异性微量输注 体内受体拮抗剂减弱口服酒精自身给药 在酒精偏爱大鼠的P和HAD系的条件下 预定-在家庭笼子中获得酒精和操作员对 口服酒精强化。 2.判断自发性与自发性是否存在直线差异 钾刺激大鼠肾上腺皮质释放DA和GABA 来自高饮酒线(P和HAD)与其低饮酒线的比较 基础条件下的饮酒者(NP和LAD品系) 对酒精挑战的反应，并识别阿片受体 介导酒精诱导的ACB释放DA的亚型。 3.确定阿片受体是否参与调节 选择性高酒精饲养大鼠的酒精厌恶阈值 摄入量(P和HAD线)。 4.确定阿片肽是否介导阿片肽的抗焦虑作用 酒精对P和HAD大鼠有明显的抑制作用。 这些实验将在有选择地为酒精饲养的大鼠身上进行 偏好和非偏好，非常适合于研究 酒精强化作用下神经系统的遗传差异 和饮酒行为。这些研究的结果将提供 更好地理解阿片系统在调解中的作用 饮酒行为的遗传差异。

This research plan addresses the hypothesis that alcohol-induced activation of the endogenous opioid system serves as a neurobiological mechanism that contributes to alcohol reinforcement and high alcohol drinking. The goal of this proposal is to determine whether opioid peptides function as neural substrates for oral alcohol self- administration and to elucidate the relationship between opioid peptides, dopamine (DA) and GABA in the ventral tegmental area (VTA) and nucleus accumbens (ACB), brain areas that are critically involved in alcohol reinforcement. To achieve these goals the following specific aims will be pursued: l. Determine whether site specific microinfusion of selective opioid receptor antagonists in vivo attenuates oral alcohol self-administration in alcohol-preferring rats of the P and HAD lines under conditions of scheduled-access to alcohol in the home cage and operant responding for oral alcohol reinforcement. 2. Determine whether there are line differences in spontaneous and potassium-stimulated DA and GABA release from the ACB in vitro in rats from the high alcohol drinking lines (P and HAD) compared with their low drinking counterparts (NP and LAD lines) under basal conditions and in response to an alcohol challenge, and identify the opioid receptor subtypes that mediate alcohol-induced DA release from the ACB. 3. Determine whether opioid receptors are involved in regulating the threshold for alcohol aversion in rats selectively bred for high alcohol intake (P and HAD lines). 4. Determine whether opioid peptides mediate the anxiolytic effect of alcohol in rats of the P and HAD lines. The experiments will be conducted using rats selectively bred for alcohol preference and nonpreference which are well suited for the study of genetic differences in neural systems that subserve alcohol reinforcement and alcohol drinking behavior. The results of these studies will provide a better understanding of the role of the opioid system in mediating genetic differences in alcohol drinking behavior.