ENKEPHALINERGIC INVOLVEMENT--VOLUNTARY ALCOHOL DRINKING

本研究项目的长期目标是确定 内源性脑啡肽是否发挥主要作用， 口服乙醇偏好的神经递质/神经调质。 将进行研究，以确定是否改变 内源性脑啡肽改变自发乙醇的作用 喝酒 具体而言，我们将研究：1）在多大程度上， 各种阿片受体拮抗剂能够抑制 自愿乙醇消费量与消费量相比 其他可口和不可口的物质，2）是否阻塞 内源性阿片受体，在初始暴露于 乙醇，阻碍了自愿的 乙醇消费，以及3）是否增加持续时间 脑啡肽的作用增强了自愿饮用乙醇。 这些 实验将需要使用自愿的老鼠， 消耗大量的乙醇。 老鼠从两个基因 已被培育为口服乙醇偏好的品系将 作为主题。 我们还建议确定中枢脑啡肽能神经系统是否 系统不同的大鼠，显示不同的偏好， 口服乙醇 具体而言，我们将确定：1）是否 脑啡肽和前脑啡肽原mRNA含量 和垂体区域不同，在乙醇幼稚大鼠， 被遗传选择为口服乙醇偏好或 非偏好，2）是否长期自愿饮酒，以及 长期摄入乙醇后， 脑啡肽和前脑啡肽原mRNA的垂体含量， 以及3）脑啡肽与脑啡肽之间是否存在真正的相关性。 前脑啡肽原mRNA含量和乙醇量 在自由选择饮酒期间自愿饮用。 这些 实验将需要使用自愿的老鼠， 消耗大量或少量的乙醇。 老鼠从四个基因 品系，其已被培育为口服乙醇偏好或 非偏好，将作为主题。 拟议研究的结果应产生更多的 关于中央机构重要性的信息 脑啡肽能系统介导的增强性能 乙醇，有助于发展和维护 异常的酒精寻求行为， 酒精中毒

The long-term objective of this research project is to determine whether endogenous enkephalins play a major role as neurotransmitters/neuromodulators of oral ethanol preference. Studies will be performed to determine whether altering the action of endogenous enkephalins changes voluntary ethanol drinking. Specifically, we will examine: 1) the extent to which various opioid receptor antagonists are capable of suppressing voluntary ethanol consumption compared with the consumption of other palatable and nonpalatable substances, 2) whether blocking endogenous opioid receptors, prior to initial exposure to ethanol, deters the initiation and development of voluntary ethanol consumption, and 3) whether increasing the duration of enkephalin action potentiates voluntary ethanol drinking. These experiments will require the use of rats which voluntarily consume large quantities of ethanol. Rats from two genetic lines, which have been bred for oral ethanol preference, will serve as subjects. We also propose to determine whether the central enkephalinergic system differs in rats that display different preferences for oral ethanol. Specifically, we will determine: 1) whether enkephalin and preproenkephalin mRNA content in discrete brain and pituitary regions differs in ethanol-naive rats which have been genetically selected for oral ethanol preference or nonpreference, 2) whether chronic voluntary ethanol drinking, and removal of ethanol following chronic consumption, alters brain and pituitary content of enkephalins and preproenkephalin mRNA, and 3) whether a true correlation exists between brain enkephalin and preproenkephalin mRNA content and the amount of ethanol voluntarily consumed during free-choice drinking. These experiments will require the use of rats which voluntarily consume high or low amounts of ethanol. Rats from four genetic lines, which have been bred for oral ethanol preference or nonpreference, will serve as subjects. The results of the proposed studies should yield additional information regarding the importance of the central enkephalinergic system in mediating the reinforcing properties of ethanol that contribute to the development and maintenance of abnormal alcohol seeking behavior which characterize human alcoholism.