Ethanol-evoked dopamine release in the nucleus accumbens core and shell

乙醇诱发伏核核和壳中的多巴胺释放

• 批准号: 7404993
• 负责人: Elaina C Howard
• 金额: $ 3.42万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7404993
• 关键词: Affect; Alcohol consumption; American; Area; Behavior; Behavioral Model; Brain; Dopamine; Dopamine Receptor; Ethanol; Laboratories; Lead; Long-Evans Rats; Measures; Mediating; Microdialysis; Monitor; Neurons; Nucleus Accumbens; Pathway interactions; Play; Process; Public Health; Receptor Up-Regulation; Relative (related person); Role; Self Administration; Stimulus; System; Testing; Transcriptional Activation; Up-Regulation; Ventral Tegmental Area; Viral; Viral Vector; alcohol effect; alcohol exposure; alcohol reinforcement; alcoholism therapy; dopaminergic neuron; drug of abuse; novel; receptor; research study; therapeutic target

DESCRIPTION (provided by applicant): Ethanol is abused by millions of Americans every year. Unfortunately, the mechanisms of ethanol reinforcement are not clear. As a result, therapy for alcohol dependence can be quite challenging. One possible therapeutic target is the mesolimbic dopaminergic system. This pathway contains dopaminergic neurons spanning from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc), and is implicated in ethanol reinforcement. However, the exact role of dopamine in ethanol reinforcement is not known. The nucleus accumbens is described as having core and shell subregions, and dopamine in these two areas may play different roles in ethanol reinforcement. One aim of this proposal is to monitor ethanol evoked dopamine release in the nucleus accumbens core and shell with microdialysis after ethanol selfadministration. These experiments will use microdiaylsis to measure dopamine levels in one of these subregions while a Long-Evans rat is responding for ethanol in an operant paradigm. This will allow comparison of any changes in dopamine between the two regions. Another aim described in this proposal will attempt to uncover the mechanism through which the core and shell are involved in ethanol selfadministration. Previously, viral-expression of dopmaine receptors has been useful in investigating the role of the nucleus accumbens in ethanol administration. However, other laboratories have not separated their manipulations of dopamine receptors into the core and shell subregions of the accumbens. In order to test whether upregulation of dopamine 1 dopamine receptors (D1DRs) are involved in ethanol reinforcement, the D1DR will be upregulated selectively in the core or shell using a sindbis viral vector. Operant ethanol selfadministration behaviors will be measured before and after the upregulation. The results of these studies will increase our understanding of dopamine's role in the reinforcing effects of ethanol, and whether the core and shell subregions play different parts in this process. Public Health Relevance: The results of this study will provide information about ethanol-evoked dopamine release and the role of the D1DR in ethanol administration. These experiments may clarify whether dopamine plays a role in ethanol reinforcement. A greater understanding of ethanol's effects on the brain is crucial to understanding why so many people are dependent on this drug of abuse.

描述（由申请人提供）：每年数以百万计的美国人滥用乙醇。不幸的是，乙醇增强的机制尚不清楚。结果，酒精依赖的治疗可能非常具有挑战性。一种可能的治疗靶标是中断多巴胺能系统。该途径含有从腹侧对接区域（VTA）到伏隔核（NACC）的多巴胺能神经元，并与乙醇增强有关。但是，多巴胺在乙醇增强中的确切作用尚不清楚。伏隔核被描述为具有核心和壳子区域，这两个区域的多巴胺在乙醇增强中起着不同的作用。该提案的目的是监测乙醇在伏隔核中的乙醇诱发的多巴胺释放，并在乙醇自我施用后具有微透析。这些实验将使用微二氧化基素来测量其中一个子区域的多巴胺水平，而长evans大鼠在操作范式中对乙醇做出反应。这将允许比较两个区域之间多巴胺的任何变化。该提案中描述的另一个目的将试图揭示核心和外壳参与乙醇自我给药的机制。以前，多普玛因受体的病毒表达在研究伏隔核在乙醇给药中的作用方面很有用。但是，其他实验室尚未将其对多巴胺受体的操纵分为伏隔族的核心和外壳子区域。为了测试多巴胺1多巴胺受体（D1DR）的上调参与乙醇增强，D1DR将使用sindbis病毒载体在核心或壳中选择性上调。在上调之前和之后，将测量手术乙醇自我给药行为。这些研究的结果将提高我们对多巴胺在乙醇增强作用中的作用以及核心和壳子区域在此过程中是否发挥不同的部分的理解。 公共卫生相关性：这项研究的结果将提供有关乙醇诱发的多巴胺释放以及D1DR在乙醇给药中的作用的信息。这些实验可能会阐明多巴胺是否在乙醇增强中起作用。对乙醇对大脑的影响的更多了解对于理解为什么这么多人依赖这种滥用药物至关重要。