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: 7289363
• 负责人: SANDRA L MORZORATI
• 金额: $ 26.46万
• 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/7289363
• 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

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）：这项竞争性延续的长期目标是确定中脑边缘多巴胺（DA）系统中长期自愿饮酒可能导致有害饮酒的神经生物学机制。我们观察到，选择性饲养的 P 大鼠长期饮酒会增加后腹侧被盖区 (VTA) 自发活跃的 DA 神经元数量，并增加伏隔核中基础细胞外 DA 浓度。此外，在乙醇剥夺期间，累积 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于 VTA DA 神经元敏感性增加所致。所提出的实验旨在证明灵敏度的提高并阐明可能的机制。细胞外记录技术和微离子电渗疗法将用于未麻醉的瘫痪 P 大鼠，以检查 VTA DA 神经元受体敏感性的变化。无网弯曲微透析实验将用于检查自由活动的 P 大鼠后 VTA 中特定神经递质的基础水平，以确定 VTA DA 神经元的变化是否由传入神经传递的改变引起。此外，电生理学和传统微透析方法将用于检查 VTA DA 神经元对随后酒精给药的增强反应性。这些研究的结果将有助于了解长期饮酒和剥夺所产生的神经适应，并可能有助于开发治疗酒精中毒的药物干预措施。