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ALCOHOL AND MESOLIMBIC DOPAMINE PATHWAY

酒精和中脑边缘多巴胺通路

基本信息

批准号：
6163743
负责人：
QINGSHAN YAN
金额：
$ 10.65万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-03-01 至 2003-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6163743
关键词：
central neural pathway /tract dopamine dopamine antagonists ethanol experimental brain lesion laboratory rat limbic system microdialysis neural transmission neuropharmacology nucleus accumbens reinforcer serotonin tetrodotoxin

项目摘要

DESCRIPTION: (Adapted from the Investigator's Abstract) The long-term goal of this project is to elucidate further the neurochemical basis of the reinforcing effects of ethanol and to develop new strategy aimed at decreasing alcoholism in man. The proposed research will be carried out on freely moving rats by using intracerebral microdialysis technique to monitor in vivo dopamine (DA) release in the nucleus accumbens (NACC), a terminal area of the mesolimbic DA pathway. Pharmacologically relevant doses of ethanol will be administered systemically. First, DA and 5-HT in 5-min dialysate samples from the NACC will be measured simultaneously following acute ethanol to detect any changes in extracellular DA and 5-HT which occur during the ascending phase of the brain ethanol concentration curve. In addition, Ethanol-induced DA release in the NACC will be compared with and without the++ treatments with: 1) perfusion with tetrodotoxin (TTX) or Ca -free medium into the NACC, both of which are known to interrupt membrane depolarization; 2) perfusion with quinpirole, a D2 receptor agonist, into the ventral tegmental area (VTA) to suppress the mesolimbic DA neuronal activity; 3) nomifensine, a DA uptake blocker. This will enable us to determine whether and to what extent a carrier-dependent mechanism is involved in ethanol-induced DA release in the NACC. Furthermore, the effects of suppression (Lesioning with 5,7-DHT) or enhancement (pretreatment with 5-hydroxytryptophan and carbidopa) of the serotonergic transmission on ethanol-induced DA release will be evaluated. This will allow us to asses the possible involvement of the 5-HT system in the reinforcing effects of ethanol, the effects of agonists and antagonists at these subtypes of 5-HT2 receptors in the reinforcing effects of ethanol, the effects of agonists and antagonists at these subtypes of 5-HT receptor on ethanol-induced DA release in the NACC will be investigated. This will elucidate the relative contribution of 5-HT2 receptors to the regulation of ethanol-induced DA release and help to explain the effects of 5-HT2 antagonists on alcohol consumption reported in the literature.

描述：(改编自《调查者摘要》)长期目标本项目的主要目的是进一步阐明神经化学基础。加强乙醇的作用并制定新的战略，旨在减少人类的酒精中毒。拟议的研究将在以下方面进行利用脑内微透析技术监测大鼠自由活动体内多巴胺(DA)在终末伏核(NACC)的释放中脑边缘多巴胺通路的区域。药理上相关的剂量乙醇将被系统地给予。首先，5分钟内的DA和5-羟色胺 NACC的透析液样本将在以下时间同时进行测量急性乙醇检测细胞外多巴胺和5-羟色胺的变化在大脑酒精浓度曲线的上升阶段。在……里面此外，乙醇诱导的NACC中DA的释放将与和不进行++处理：1)河豚毒素(TTX)或 -游离介质进入NACC，这两种物质都已知会中断膜去极化；2)用D2受体激动剂奎比罗灌流腹侧被盖区(VTA)抑制中脑边缘DA神经元活性；3)诺米芬辛，一种DA摄取阻断剂。这将使我们能够确定是否以及在多大程度上依赖于载体参与乙醇诱导的NACC中DA的释放。此外，抑制(5，7-二羟色胺损毁)或增强(预处理)的效果 5-羟色氨酸和卡比多巴)的5-羟色胺能传递将对乙醇诱导的DA释放进行评估。这将使我们能够 5-羟色胺系统可能参与脑缺血再灌流的强化作用乙醇、激动剂和拮抗剂对5-HT2亚型的影响乙醇增强效应中的受体、激动剂和 5-羟色胺受体各亚型拮抗剂对乙醇诱导的多巴胺释放的影响将在NACC接受调查。这将澄清相关的 5-HT2受体在乙醇诱导的多巴胺调节中的作用释放并帮助解释5-HT2拮抗剂对酒精的影响在文献中报告了消费。