VTA DA Neuron Electrophysiology In Selected Rat Lines

选定大鼠系的 VTA DA 神经元电生理学

• 批准号: 7487004
• 负责人: SANDRA L MORZORATI
• 金额: $ 26.39万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7487004
• 关键词: Agonist; Alcohol consumption; Alcohols; Breeding; Chronic; Development; Dopamine; Electrophysiology (science); Ethanol; Intervention; Lead; Methods; Microdialysis; N-Methylaspartate; Neurons; Neurotransmitters; Nucleus Accumbens; Numbers; Paralysed; Rat-1; Rattus; Techniques; Testing; Ventral Tegmental Area; Water; Week; alcohol abuse therapy; chronic alcohol ingestion; deprivation; design; dopamine system; dopaminergic neuron; extracellular; gamma-Aminobutyric Acid; mesolimbic system; neuroadaptation; neurobiological mechanism; neurochemistry; neurotransmission; receptor sensitivity; research study; response

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.

这种竞争延续的长期目标是确定神经生物学机制 长期自愿酒精摄入量的中脑脱脂胺（DA）系统可能导致 有害饮酒。我们观察到有选择性繁殖的P大鼠长期消费量 增加了后腹侧对段区域（VTA）的自发活性DA神经元的数量和 伏隔核中的基础细胞外DA浓度增加。此外， 在乙醇剥夺期间，伏托da的水平持续存在。我们假设观察到 电生理和神经化学变化是由VTA DA神经元的灵敏度提高而产生的。 提出的实验旨在证明灵敏度的提高并阐明了可能 机制。细胞外记录技术和微观噬菌体将用于未经麻醉 瘫痪的P大鼠检查VTA DA神经元受体敏感性的变化。无网络 微透析实验将用于检查后部特定神经递质的基础水平 自由移动的P大鼠的VTA，以确定VTA DA神经元的变化是否导致传入的改变导致 神经传递。此外，电生理学和传统的微透析方法都将用于 检查VTA DA神经元对随后的酒精给药的反应性提高。这 这些研究的结果将提供对慢性酒精产生的神经适应的理解 饮酒和剥夺，可能有助于发展药理干预措施 酒精中毒的治疗。