BRAIN DIALYSIS AND ETHANOL SELF ADMINISTRATION

本提案旨在扩大以前在这方面的工作 旨在识别神经元回路和神经化学物质的实验室 参与乙醇奖赏和依赖的底物。这就是目的 使用颅内微透析技术来 监测几种前脑递质的突触浓度 之前与酒精寻求行为和奖励有牵连，并 建立基础神经递质和酒精诱导神经递质的“档案” 未选择的Wistar和偏爱酒精的(P-1)大鼠的活动。 在口服乙醇之前和期间，将监测递质的释放 两级自由选择中的自我给药(水/乙醇10%w/v) 在条件下，使用依赖的大鼠进行酒精戒断。 此外，酒精摄入量的高、低响应者。透析液遗嘱 取自伏核、尾状核和腹侧核 并将进行多巴胺(DA)、5-羟色胺(5-羟色胺)(5- 羟色胺)或γ-氨基丁酸(GABA)。这些数据将有助于确定 两种品系大鼠基础多巴胺、5-羟色胺和GABA水平的差异 他们对乙醇的偏好不同，建立了神经化学 乙醇自身给药对上述物质释放的影响 递质，并将有助于确定它们在乙醇奖励和 依赖。最后，酒精对神经递质活性的影响 将与其他滥用药物进行比较，包括可卡因和 关于海洛因，这些研究具有重要的意义 了解乙醇对中枢神经递质系统的作用 酒精奖赏神经底物的识别。这类问题 对于制定有效的战略至关重要 用于预防和治疗酒精滥用和依赖。

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.