Neurosteroid Modulation of Ethanol Intake and Reward

神经类固醇对乙醇摄入和奖励的调节

• 批准号: 6836291
• 负责人: MATTHEW M FORD
• 金额: $ 4.73万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6836291
• 关键词: GABA receptor; alcoholic beverage consumption; brain electrical activity; dopamine; drug interactions; enzyme inhibitors; ethanol; genetically modified animals; laboratory mouse; microdialysis; neural transmission; neuropharmacology; neuroregulation; neurotransmitter metabolism; nucleus accumbens; postdoctoral investigator; pregnanolone; receptor binding; reinforcer; self medication; steroid metabolism; sulfates; sulfonate; sulfotransferase; tegmentum

DESCRIPTION (provided by applicant): The goal of the proposed research is to delineate a mechanistic role for the neurosteroid allopregnanolone (ALLOP) at the level of the ventral tegmental area (VTA) on ethanol self-administration patterns and brain reward pathway activation. Gamma-aminobutyric acid type A (GABA-A) receptors in the VTA are thought to mediate, in part, ethanol's subjective and motivational effects; presumably via modulation of the mesolimbic dopaminergic projection from the VTA to the nucleus accumbens (NAc). The neurosteroid ALLOP, an endogenous positive modulator of GABA-A receptors, has been demonstrated to potentiate maintained and reinstated operant responding for ethanol as well as augment ethanol self-administration. The first specific aim will determine the effects of manipulating the levels and metabolism (sulfonation) of ALLOP within the VTA on established ethanol consumption patterns in mice. Studies in the second research aim will assess the impact of VTA-applied ALLOP on NAc DA and will evaluate ALLOP's interaction with ethanol-stimulated changes in extracellular NAc DA levels. Results from these experiments will provide valuable insights into the mechanisms underlying neurosteroid modulation of ethanol intake and reward.

描述（由申请人提供）：拟议研究的目标是描述神经类固醇四氢孕酮（ALLOP）在腹侧被盖区（VTA）水平对乙醇自我给药模式和大脑奖赏通路激活的机制作用。 VTA 中的 A 型γ-氨基丁酸 (GABA-A) 受体被认为在一定程度上介导乙醇的主观和动机效应；推测是通过调节从 VTA 到伏隔核 (NAc) 的中脑边缘多巴胺能投射。神经类固醇 ALLOP 是 GABA-A 受体的内源性正调节剂，已被证明可以增强对乙醇的维持和恢复操作反应，并增强乙醇的自我给药。第一个具体目标是确定控制 VTA 内 ALLOP 的水平和代谢（磺化）对小鼠既定乙醇消耗模式的影响。第二个研究目标的研究将评估应用 VTA 的 ALLOP 对 NAc DA 的影响，并将评估 ALLOP 与乙醇刺激的细胞外 NAc DA 水平变化的相互作用。这些实验的结果将为了解神经类固醇调节乙醇摄入和奖励的机制提供有价值的见解。