ETHANOL SEEKING & INTAKE: MICRODIALYSIS/DA/GABA

寻找乙醇

• 批准号: 6918101
• 负责人: KIMBERLY A LEITE-MORRIS
• 金额: $ 14.78万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-25 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6918101
• 关键词: GABA receptor; alcoholic beverage consumption; amygdala; behavioral /social science research tag; craving; dopamine; ethanol; high performance liquid chromatography; laboratory mouse; laboratory rat; microdialysis; microinjections; neuropharmacology; neuropsychology; nucleus accumbens; reinforcer; species difference; substance abuse related behavior

DESCRIPTION (provided by applicant): The proposed project will prepare the applicant for a career as an independent research scientist investigating the neurochemical mechanisms that underlie the motivational and reinforcing aspects of alcohol-directed behaviors. Alcohol-directed behaviors can be conceptually divided into two phases: 1) appetitive or alcohol seeking and 2) consumption or alcohol drinking. It is hypothesized that activation of the GAB A receptor system exerts ethanol-directed behavior, The overall goal of this proposal is to examine whether midbrain GAB A (A) and (B) receptor systems modulate mesolimbic dopamine during the two phases of alcohol drinking behavior: seeking and consumption. Together these two components regulate alcohol intake and although certain aspects of their function may overlap in humans, they can be studied independently in a rodent model. Mesolimbic pathways from the ventral tegmental area to the nucleus accumbens (NAc) and central nucleus of the amygdala (Amg) have a major role in regulating both the motivational and consummatory behaviors related to alcohol use. However, changes in the level of mesolimbic dopamine in these brain regions have only been investigated during the drinking phase. Extracellular levels of dopamine will be evaluated in the nucleus accumbens and central nucleus of the amygdala. Aim 1 (rats and mice) will characterize the pattern of change of dopamine during ethanol seeking and consumption. Aim 2 (rats) will examine the role of GABA (A) and (B) receptor agonist effects on dopamine levels during ethanol seeking and consumption. Aim 3 will examine dopamine levels in GABA (A) receptor alpha knockout mice during alcohol seeking and consumption. The mentoring team will be comprised of leaders in alcohol and addiction research and the proposed research and career development plan will provide extensive training including the theoretical and practical aspects of operant conditioning, and utilization of in vivo microdialysis and HPLC for the assessment of extracellular dopamine levels in an across species paradigm. This novel approach will characterize the circuitry and specific neurotransmitter systems involved in ethanol-directed behaviors. These findings may lead to a pharmacological treatment that will attenuate alcohol "craving" and alcohol drinking. The project will assess the motivational and reinforcing aspects of alcohol underlying neurocircuitry and receptor mechanisms that will recipitate the planning of an RO1.

描述（由申请人提供）：拟议的项目将使申请人成为一名独立研究科学家的职业，研究神经化学机制是基于酒精指导行为的动机和加强方面的基础。酒精指导的行为可以在概念上分为两个阶段：1）食欲或饮酒以及2）消费或饮酒。假设GAB A受体系统的激活施加了乙醇指导的行为，该提案的总体目标是检查中脑GAB A（A）和（B）受体系统是否在饮酒行为的两个阶段调节中龙多巴胺。这两个组件共同调节酒精摄入量，尽管其功能的某些方面可能与人类重叠，但可以在啮齿动物模型中独立研究它们。杏仁核（AMG）的腹侧偏段区域到伏隔核（NAC）和中央核（AMG）中的中侧途径在调节与酒精使用相关的动机和完善行为方面具有重要作用。 然而，仅在饮酒阶段研究了这些大脑区域中中唇多巴胺水平的变化。细胞外多巴胺的水平将在伏隔核和杏仁核的中央核中进行评估。 AIM 1（大鼠和小鼠）将表征在寻求乙醇和消费期间多巴胺变化的模式。 AIM 2（大鼠）将检查GABA（a）和（b）受体激动剂对乙醇寻求和消费期间多巴胺水平的作用的作用。 AIM 3将检查GABA（A）受体α敲除小鼠在寻求和消费期间的多巴胺水平。指导团队将由酒精和成瘾研究领域的领导者组成，拟议的研究和职业发展计划将提供广泛的培训，包括操作条件的理论和实际方面，以及对体内微透析和HPLC的利用，用于评估跨种类范围内细胞外多巴胺水平的评估。这种新颖的方法将表征参与乙醇指导行为的电路和特定的神经递质系统。这些发现可能会导致药理学治疗，从而减轻酒精“渴望”和饮酒。该项目将评估饮酒基础神经通路和受体机制的动机和增强方面，这些机制将对RO1的规划进行处理。