NEUROPHARMACOLOGY OF ETHANOL REINFORCEMENT

乙醇在人体内具有增强作用， 酒精滥用和酒精中毒。 在大鼠中，乙醇易于自我给药 当通过将大鼠预先暴露于 甜的解决方案 非依赖性和非剥夺性大鼠会选择 在有限的情况下，乙醇超过水，并将自我管理 足以产生有意义的血液乙醇水平。 工作 试图确定乙醇中的特定神经递质 最近的研究表明，低剂量的乙醇可以释放出 多巴胺在脑桥核区域，多巴胺激动剂 似乎在不减少水摄入量的情况下减少了对乙醇的偏好。 的 脑桥核是边缘-前脑的汇聚点之一， 锥体外系回路，其他强化药物如可卡因 而海洛因可能会产生强化作用。 的目的 目前的建议是审查核心组织的作用， 乙醇强化中的传入和传出联系。 非 将训练剥夺的雄性Wistar和雄性酒精偏好（P）大鼠 每天30分钟使用糖精褪色自行服用乙醇 out程序。 中脑皮质边缘多巴胺投射在 将使用6-羟基多巴胺损伤来测试脑桥核， 丘脑核 其他传入神经对丘脑核的作用 将使用杏仁核的细胞体（鹅膏蕈氨酸）损伤进行检查 和海马 传出神经回路在核团中的作用 将使用细胞体（鹅膏蕈氨酸）病变检查骨肉瘤， 腹侧苍白球和其他传出神经 连接. 假设特定神经递质的功能 将通过微量注射激动剂来检查调节该回路的方法， 阿片肽、神经降压素、谷氨酸和胆囊收缩素的拮抗剂 进入丘脑腹侧核或腹侧苍白球。 这些拟议 与已发表或正在进行的神经药理学研究平行的研究 精神和鸦片强化，因此将提供一种手段， 评价乙醇底物的相似性和独特性 加固. 这些结果不仅具有重要的意义， 对我们理解酒精中毒的神经生物学有帮助， 导致发展可行的药理学干预， 酒精中毒

Ethanol has reinforcing properties in man that presumably contribute to alcohol abuse and alcoholism. In rats ethanol is readily self-administered orally when taste factors are minimized by pre-exposing the rats to sweetened solutions. Non-dependent and non-deprived rats will choose ethanol over water in limited access situations and will self-administer sufficient quantities to produce meaningful blood ethanol levels. Work attempting to identify specific neurotransmitters involved in ethanol reinforcement has recently shown that low doses of ethanol can release dopamine in the region of the nucleus accumbens and that dopamine agonists appear to reduce ethanol preference without decreasing water intake. The nucleus accumbens is one of the converging points for a limbic-forebrain- extrapyramidal circuit upon which other reinforcing drugs such as cocaine and heroin may act to produce their reinforcing effects. The purpose of the present proposal is to examine the role of the nucleus accumbens and its afferent and efferent connections in ethanol reinforcement. Non- deprived male Wistar and male Alcohol Preferring (P) rats will be trained to self-administer ethanol in daily 30 min sessions using a saccharin fade out procedure. The role of the mesocorticolimbic dopamine projections to the nucleus accumbens will be tested using 6-hydroxydopamine lesions to the nucleus accumbens. The role of other afferents to the nucleus accumbens will be examined using cell body (ibotenic acid) lesions of the amygdala and hippocampus. The role of neural circuitry efferent to the nucleus accumbens will be examined using cell body (ibotenic acid) lesions of the nucleus accumbens itself, the ventral pallidum, and other efferent connections. The function of specific neurotransmitters hypothesized to modulate this circuitry will be examined by microinjection of agonists and antagonists of opioid peptides, neurotensin, glutamate and cholecystokinin into either the nucleus accumbens or ventral pallidum. These proposed studies parallel published or ongoing studies on the neuropharmacology of psychomotor and opiate reinforcement and as such will provide a means to evaluate the similarities and uniqueness of the substrates for ethanol reinforcement. These results should have important implications not only for our understanding of the neurobiology of ethanol intoxication but may lead to the development of viable pharmacological intervention in alcoholism.