VTA DA Neuron Electrophysiology In Selected Rat Lines

这一竞争性延续的长期目标是确定神经生物学机制， 中脑边缘多巴胺（DA）系统是长期自愿饮酒的基础，可能导致 有害的酒精消费。我们观察到选择性饲养的P大鼠的慢性酒精消耗 增加后腹侧被盖区（VTA）自发活动的DA神经元数量， 增加基底细胞外多巴胺浓度在延髓核。此外， 在乙醇剥夺期间，多巴胺水平持续存在。我们假设观察到的 腹侧被盖区DA神经元的敏感性增加引起了电生理和神经化学的变化。 拟议的实验旨在证明增加的灵敏度和阐明可能的 机制等细胞外记录技术和微离子导入将用于未麻醉的 麻痹P大鼠，以检查VTA DA神经元上受体敏感性的变化。无网挠 微透析实验将用于检查特定神经递质的基础水平， 自由活动P大鼠的VTA，以确定VTA DA神经元的变化是否由传入神经元的改变引起。 神经传递此外，电生理和传统的微透析方法将用于 检查腹侧被盖区DA神经元对随后的酒精给药的高度反应性。的 这些研究的结果将有助于理解长期饮酒所产生的神经适应性 饮酒和剥夺，并可能有助于药物干预的发展， 治疗酒精中毒。

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.