BRAIN DIALYSIS AND ETHANOL SELF-ADMINISTRATION

本建议旨在扩展以前的工作， 实验室旨在确定神经元电路和神经化学 底物参与乙醇奖励和依赖。才是目的 利用颅内微透析技术， 监测几种前脑递质的突触浓度 以前参与乙醇寻求行为和奖励， 建立基础和乙醇诱导神经递质的“谱” 对Wistar大鼠和嗜酒（P-1）大鼠的活性。 在口服乙醇之前和期间监测发射器释放 在两个杠杆自由选择中自我给药（水/乙醇10%w/v） 条件下，使用依赖性大鼠进行乙醇戒断。 此外，高和低反应的乙醇摄入量。透析液将 从延髓核、尾状核和腹 苍白球，并将测定多巴胺（DA），5-羟色胺（5- HT）或γ-氨基丁酸（GABA）。这些数据将用于识别 两种品系大鼠基础DA、5-HT和GABA水平的差异 他们对乙醇的偏好不同，建立了神经化学 自我管理的乙醇对这些释放的影响 发射机，并将有助于确定他们的作用，乙醇奖励， 依赖最后，乙醇对神经递质活性的影响 将与包括可卡因在内的其他滥用药物进行比较， 海洛因，这些研究对于 了解乙醇对中枢神经递质系统的作用， 乙醇奖励的神经基质的识别。等问题 对制定有效战略至关重要 用于预防和治疗乙醇滥用和依赖。

The present proposal is designed to extend previous work in this laboratory aimed at identifying neuronal circuitries and neurochemical substrates involved in ethanol reward and dependence. It is the purpose of this project to use the intracranial microdialysis technique to monitor the synaptic concentration of several forebrain transmitters previously implicated in ethanol seeking behavior and reward, and to establish a "profile" of basal and ethanol-induced neurotransmitter activity for both unselected Wistar and alcohol-preferring (P-1) rats. Transmitter release will be monitored before and during oral ethanol self-administration in a two-lever free-choice (water/ethanol 10%w/v) condition, using dependent rats undergoing ethanol withdrawal. Additionally, high and low responders for ethanol intake. Dialysate will be collected from the nucleus accumbens, caudate nucleus and ventral pallidum, and will be assayed for dopamine (DA), 5-hydroxytryptamine (5- HT) or gamma-aminobutyric acid (GABA). These data will serve to identify differences in basal DA, 5-HT and GABA levels between two strains of rats differing in their preference for ethanol, establish the neurochemical effects of self-administered ethanol on the release of these transmitters, and will help determine their role in ethanol reward and dependence. Finally, the effects of ethanol on neurotransmitter activity will be compared to those of other drugs of abuse including cocaine and heroin, These studies have important implications with regard to the understanding of ethanol actions on central neurotransmitter systems and the identification of neural substrates for ethanol reward. Such issues are of critical importance for the development of effective strategies for the prevention and treatment of ethanol abuse and dependence.