ENKEPHALINERGIC INVOLVEMENT--VOLUNTARY ALCOHOL DRINKING

这项研究项目的长期目标是确定 内源性脑啡肽是否在 口服酒精偏好的神经递质/神经调节剂。 将进行研究，以确定是否改变 内源性脑啡肽的作用改变自愿性乙醇 喝酒。具体来说，我们将检查：1)在多大程度上 不同的阿片受体拮抗剂能够抑制 自愿乙醇消费与#年的消费相比 其他可口和不可口物质，2)是否堵塞 内源性阿片受体，在首次暴露于 乙醇，阻碍了自愿的发起和发展 乙醇消耗，以及3)是否增加酒精消耗的持续时间 脑啡肽的作用增强了自愿饮用酒精的能力。这些 实验将需要使用自愿使用的老鼠 消耗大量的乙醇。来自两个基因的大鼠 为口服乙醇偏好而培育的品系，将 作为受试者。 我们还建议确定中枢脑啡肽能 表现出不同偏好的大鼠的系统不同 口服乙醇。具体来说，我们将确定：1)是否 不同脑区脑啡肽和前脑啡肽原mRNA的含量 而在酒精缺乏的大鼠中，垂体区域有所不同 因口服酒精偏好而被遗传选择或 无偏好，2)是否长期自愿饮酒，以及 长期饮酒后戒掉酒精会改变大脑 以及脑啡肽和前脑啡肽原基因的含量， 3)脑内脑啡肽之间是否存在真实的相关性 和前脑啡肽原信使核糖核酸含量及乙醇量 在自由选择饮酒期间自愿饮用。这些 实验将需要使用自愿使用的老鼠 消耗高或低数量的乙醇。来自四个基因的大鼠 品系，已培育为口服乙醇偏好或 无偏好，将作为研究对象。 拟议研究的结果应产生额外的 关于中央银行重要性的信息 脑啡肽能系统在调节脑血管紧张素转换酶增强特性中的作用 乙醇有助于开发和维护 人类的反常寻酒行为 酗酒。

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.