Dopamine neuron activity during operant ethanol reinforcement

操作性乙醇强化过程中​​的多巴胺神经元活动

• 批准号: 7217153
• 负责人: William Maurice Doyon
• 金额: $ 5.11万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7217153
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; behavioral /social science research tag; biological signal transduction; catheterization; cues; dopamine; ethanol; high performance liquid chromatography; laboratory rat; microdialysis; neurons; neuropharmacology; neuropsychology; nucleus accumbens; operant conditionings; postdoctoral investigator; reinforcer; self medication; tegmentum

DESCRIPTION (provided by applicant): PROJECT SUMMARY. The mechanisms involved in the development of ethanol reinforcement are not fully understood. Despite the broad action of ethanol in the brain, the activation of mesolimbic dopamine (DA) neurons may represent a key systems-level process involved in goal-directed behavior and adaptive responding to the environment. Although different paradigms show that ethanol directly stimulates mesolimbic DA neurons, the involvement of DA in ethanol-reinforced behavior remains controversial. We hypothesize that (1) DA neuron activity increases transiently during ethanol self-administration and that (2) the increase is related to ethanol stimulus cues and not to ethanol action upon the DA system. The major goal of the proposed study is to distinguish DA neuron activity in real time during operant responding, during the initial phase of ethanol consumption, and later after brain ethanol has reached pharmacological levels. During these specific periods of a self-administration session, we will monitor the firing activity of multiple DA neurons in the ventral tegmental area simultaneously with multiunit recording techniques. To determine the direct pharmacological effect of ethanol on DA signaling, we will administer ethanol in freely moving rats via an intraperitoneal catheter at a rate that approximates the pharmacokinetics of ethanol during self-administration. This approach will allow us to better understand the behavioral correlates involved in the DA response during self-administration. During these procedures, we will also quantify the DA concentration in the nucleus accumbens with microdialysis to better understand the relationship between DA neuron excitability and the release of DA at the terminal regions during ethanol administration. RELEVANCE. Alcohol abuse and dependence continue to cause major health and societal problems. However, the neuronal mechanisms that underlie this destructive behavior remain ambiguous. These experiments will provide important new insight into how brain regions that are implicated in drug addiction process information during motivated alcohol drinking.

描述（申请人提供）：项目摘要。尚不完全了解乙醇增强发展的机制。尽管乙醇在大脑中采取了广泛的作用，但中唇多巴胺（DA）神经元的激活可能代表参与目标指导行为和对环境的适应性响应的关键系统级过程。尽管不同的范式表明乙醇直接刺激中唇DA神经元，但DA参与乙醇增强的行为仍然存在争议。我们假设（1）D​​A神经元活性在乙醇自我给药过程中会瞬时增加，并且（2）增加与乙醇刺激提示有关，而不是乙醇对DA系统的作用。拟议研究的主要目的是在操作响应期间，在乙醇消耗的初始阶段以及脑乙醇达到药理水平后的最初阶段，在操作人员响应期间实时区分DA神经元活性。在自我管理会议的这些特定时期，我们将通过多单位记录技术同时监测腹侧对段区域中多个DA神经元的发射活性。为了确定乙醇对DA信号传导的直接药理作用，我们将以腹膜内导管的自由移动大鼠施用乙醇，以近似于自我管理过程中乙醇的药代动力学的速率。这种方法将使我们能够更好地理解自我管理过程中DA响应所涉及的行为相关性。在这些过程中，我们还将用微透析量化伏隔核中的DA浓度，以更好地了解DA神经元兴奋性与乙醇给药期间末端区域DA释放之间的关系。 关联。酗酒和依赖继续引起重大的健康和社会问题。 但是，这种破坏性行为的基础的神经元机制仍然模棱两可。这些实验将提供重要的新见解，了解在动机饮酒过程中如何与药物成瘾过程信息有关的大脑区域。