VTA DA Neuron Electrophysiology In Selected Rat Lines

贺龙-本次竞赛的长期目标是确定脑出血的神经生物学机制 中脑边缘多巴胺系统是长期自愿饮酒的基础，可能导致 有害的酒精消费。我们观察到选择性繁殖的P大鼠长期饮酒 增加后腹侧被盖区(VTA)自发活动的DA神经元的数量； 伏隔核基础细胞外多巴胺浓度升高。此外，在变化中， 伏隔区DA水平在酒精剥夺期间持续存在。我们假设观察到的 VTA DA神经元的敏感性增加引起电生理和神经化学改变。 拟议的实验旨在证明更高的灵敏度并阐明可能 机械装置。细胞外记录技术和微离子导入技术将用于未麻醉的 使P大鼠瘫痪，观察VTA DA神经元受体敏感性的变化。无净伸缩 微透析实验将被用来检测后脑特定神经递质的基础水平。 自由活动P鼠的VTA以确定VTA DA神经元的变化是否源于传入神经元的改变 神经传递。此外，电生理和传统的微透析方法将被用于 检查VTA DA神经元对随后的酒精注射的高反应性。这个 这些研究的结果将提供对慢性酒精所产生的神经适应的理解 饮酒和剥夺，并可能有助于开发针对老年人的药物干预 酒精中毒的治疗。

he long-term objective of this competing continuation is the identification of neurobiological mechanisms in the mesolimbic dopamine (DA) system underlying prolonged voluntary alcohol intake that may lead to harmful alcohol consumption. We observed that chronic alcohol consumption by selectively-bred P rats increased the number of spontaneously active DA neurons in the posterior ventral tegmental area (VTA) and increased basal extracellular DA concentrations in the nucleus accumbens. Furthermore, the alterations in accumbal DA levels persisted during ethanol deprivation. We hypothesize that the observed electrophysiological and neurochemical changes resulted from an increased sensitivity of VTA DA neurons. The proposed experiments are designed to demonstrate increased sensitivity and elucidate possible mechanisms. Extracellular recording techniques and microiontophoresis will be used in unanesthetized paralyzed P rats to examine changes in the sensitivities of receptors on VTA DA neurons. No-net-flex microdialysis experiments will be used to examine basal levels of specific neurotransmitters in the posterior VTA of freely moving P rats to determine if changes in VTA DA neurons result from alterations in afferent neurotransmission. In addition, both electrophysiological and traditional microdialysis methods will be used to examine the heightened responsiveness of VTA DA neurons to subsequent alcohol administration. The results of these studies will provide an understanding of the neuroadaptations produced by chronic alcohol drinking and deprivation and may contribute to the development of pharmacological interventions for the treatment of alcoholism.