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: 7144298
• 负责人: SANDRA L MORZORATI
• 金额: $ 27.27万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7144298
• 关键词: NMDA receptors; action potentials; alcoholic beverage consumption; alcoholism /alcohol abuse; cryostat; dopamine; dopamine receptor; electrophysiology; genetic susceptibility; iontophoresis therapy; laboratory rat; mesencephalon; neurons; neuroregulation; preference; stimulant /agonist; substance abuse related behavior; substantia nigra

DESCRIPTION (provided by applicant): The 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.

描述（由申请人提供）：这种竞争性延续的长期目标是鉴定了长期自愿酒精摄入量的中唇糖多巴胺（DA）系统中神经生物学机制，这可能会导致有害的酒精消耗。我们观察到，选择性繁殖的P大鼠的慢性饮酒增加增加了腹侧侧瓣区域（VTA）自发活性DA神经元的数量，并增加了伏隔核中基础细胞外DA浓度的增加。此外，在乙醇剥夺期间，伏托dA水平的变化持续存在。我们假设观察到的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的机制。细胞外记录技术和微观滴虫将在未消除的瘫痪P大鼠中使用，以检查受体对VTA DA神经元的敏感性的变化。无网络FLEX微透析实验将用于检查自由移动P大鼠后VTA中特定神经递质的基础水平，以确定VTA DA神经元的变化是否是由于传入神经传递的改变而导致的。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响应性的提高。这些研究的结果将提供对长期饮酒和剥夺产生的神经适应的理解，并可能有助于开发用于治疗酒精中毒的药理干预措施。