CNS SITES MEDIATING ALCOHOL DRINKING BEHAVIOR

调节饮酒行为的中枢神经系统站点

• 批准号: 6509236
• 负责人: JAMES M MURPHY
• 金额: $ 26.08万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6509236
• 关键词: GABA receptor; alcoholic beverage consumption; behavior test; behavioral /social science research tag; dopamine; dopamine receptor; dorsal raphe nucleus; ethanol; laboratory rat; lenticular nucleus; microdialysis; neuroanatomy; neuropharmacology; neurotransmitter receptor; nucleus accumbens; serotonin receptor; substance abuse related behavior; tegmentum

DESCRIPTION: (Adapted from the Investigator's Abstract) The overall goal of the projects in this proposal is to identify CNS sites and receptors involved in mediating ethanol (E) drinking behavior. The primary focus will be on the mesocorticolimbic dopamine (DA) system, emanating from cell bodies in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAC) shell, medial prefrontal cortex (MPC), and ventral pallidum (VP). The dorsal raphe nucleus (DRN) will also be investigated, which sends serotonin (5-HT) projections to the DA system. A general working hypothesis is that the mesocorticolimbic DA system mediates the reinforcing properties of E, and activity within this DA system is regulated by various autoreceptors, and pre- and post-synaptic receptors. It is assumed that hereditary influences can predispose high E drinking behavior through genetic effects on neurobiological substrates within the neurotransmitter systems and receptors being investigated. Thus, to accomplish the overall goal, rats selectively bred for high alcohol intake, the P, HAD1 and HAD2 lines, will be used as models. The strategy will be to conduct experiments in rats of the P line, and then to confirm key findings in the HAD replicate lines. Three experimental techniques will be used. First, the effects on E drinking in a limited access paradigm will be assessed after CNS site-specific microinjections of receptor agents for DA, 5-HT and GABAA receptors. Selected receptor agents for subtypes will be tested at each CNS site; the VTA, NAc, VP, MPC and DRN. Second, microdialysis will be utilized to assess the extracellular levels of DA in the VTA, NAc, VP, and MPC during ongoing E self administration in an operant paradigm. Third, the reinforcing actions of E at three prospective sites, the NAc, VP and MPC, will be investigated by utilizing an intracranial self administration (ICSA) procedure. The findings will further knowledge regarding the role of the mesocorticolimbic DA system in the reinforcing consequences of E ingestion, and should delineate the importance of certain neurotransmitter receptor subtypes regulating this DA system and mediating ethanol self administration.

描述：（改编自研究者摘要） 本提案中项目的总体目标是确定CNS站点， 参与介导乙醇（E）饮酒行为的受体。主 重点将放在中皮质边缘多巴胺（DA）系统，从 腹侧被盖区（VTA）的细胞体，并投射到核 内侧前额叶皮质（MPC）和腹侧苍白球 （副总统）。中缝背核（DRN）也将被研究，它发送 5-羟色胺（5-HT）投射到DA系统。一般的工作假设是 中皮层边缘DA系统介导E的增强特性， 并且该DA系统内的活性由各种自身受体调节，并且 突触前和突触后受体。假设遗传影响可以 通过遗传对神经生物学的影响使高E饮酒行为易感 神经递质系统和受体内的底物 研究了因此，为了实现总体目标，大鼠选择性地繁殖， 高酒精摄入，P，HAD 1和HAD 2线，将被用作模型。的 策略将是在P系大鼠中进行实验，然后 证实了HAD重复系中的关键发现。三种实验技术 将用于第一，在有限获取范例中对E饮用的影响 将在CNS部位特异性显微注射受体药物后进行评估， DA、5-HT和GABAA受体。针对亚型选择的受体药物将是 在每个CNS部位进行检测; VTA、NAc、VP、MPC和DRN。二、微透析 将用于评估VTA，NAc，VP， 和MPC在持续的E自我管理在操作性范例。三是 在NAc、VP和MPC这三个预期地点加强E行动，将 通过颅内自我给药（ICSA）进行研究 procedure.这些发现将进一步了解 中皮质边缘DA系统在E摄入的强化后果中，以及 应该描述某些神经递质受体亚型的重要性， 调节该DA系统并介导乙醇自我给药。