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

基本信息

批准号：
7483759
负责人：
William Maurice Doyon
金额：
$ 5.59万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
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/7483759
关键词：
Acute Adaptive Behaviors Affect Alcohol abuse Alcohol consumption Animals Appetitive Behavior Behavior Behavioral Brain Brain region Cannulas Catheters Computer information processing Consumption Cues Data Dependence Development Dopamine Dose Drug Addiction Drug Kinetics Drug effect disorder Environment Ethanol Fire - disasters Goals Health High Pressure Liquid Chromatography In Vitro Incentives Learning Measurement Methodology Microdialysis Monitor Motivation Neurons Nucleus Accumbens Odors Phase Procedures Process Psychological reinforcement Rate Rattus Resolution Role Route Schools Self Administration Sensory Signal Transduction Solutions Stimulus System Taste Perception Techniques Testing Time Training Ventral Tegmental Area alcohol cue alcohol effect alcohol reinforcement classical conditioning dopamine system dopaminergic neuron extracellular in vivo insight intraperitoneal mesolimbic system neuromechanism reinforced behavior research study response transmission process

项目摘要

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（由申请人提供）：项目摘要。乙醇强化发展所涉及的机制尚不完全清楚。尽管乙醇在大脑中具有广泛的作用，但中脑边缘多巴胺（DA）神经元的激活可能代表了涉及目标导向行为和对环境的适应性反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脑边缘 DA 神经元，但 DA 参与乙醇强化行为仍然存在争议。我们假设 (1) DA 神经元活性在乙醇自我给药期间短暂增加，并且 (2) 这种增加与乙醇刺激线索有关，而不是与乙醇对 DA 系统的作用有关。该研究的主要目标是在操作反应期间、乙醇消耗的初始阶段以及脑乙醇达到药理学水平后实时区分 DA 神经元活动。在自我管理过程的这些特定时期，我们将使用多单元记录技术同时监测腹侧被盖区多个 DA 神经元的放电活动。为了确定乙醇对 DA 信号传导的直接药理作用，我们将通过腹膜内导管对自由活动的大鼠施用乙醇，其速率近似于自我施用期间乙醇的药代动力学。这种方法将使我们能够更好地理解自我管理期间 DA 反应所涉及的行为相关性。在这些过程中，我们还将通过微透析量化伏隔核中的 DA 浓度，以更好地了解乙醇给药期间 DA 神经元兴奋性与末端区域 DA 释放之间的关系。关联。酒精滥用和依赖继续造成重大的健康和社会问题。然而，这种破坏性行为背后的神经机制仍然不明确。这些实验将为了解与毒瘾有关的大脑区域在主动饮酒期间如何处理信息提供重要的新见解。