CNS SITES MEDIATING ALCOHOL DRINKING BEHAVIOR

描述：(改编自《调查者摘要》) 该提案中项目的总体目标是确定CNS站点和 参与调节酒精(E)饮酒行为的受体。初级阶段 重点将放在中皮质边缘多巴胺(DA)系统上，该系统源于 腹侧被盖区(VTA)内的胞体并投射到细胞核 伏隔核(NAC)壳、内侧前额叶皮质(MPC)和腹侧苍白球 (副总裁)。中缝背核(DRN)也将被研究，它发出 5-羟色胺(5-羟色胺)投射到DA系统。一个普遍的工作假设是 中皮质边缘DA系统介导了E的增强特性， 这个DA系统内的活动受各种自身受体的调节，并且 突触前和突触后受体。据推测，遗传影响可以 神经生物学遗传效应使高E饮酒行为易感 神经递质系统和受体内的底物是 调查过了。因此，为了实现总体目标，有选择地饲养大鼠 高酒精摄入量，P，HAD1和HAD2品系，将被用作模型。这个 策略将是在P线大鼠身上进行实验，然后 确认HAD复制品系中的关键发现。三种实验技术 将会被使用。首先，在有限获取范式下，电子饮酒对电子饮酒的影响 将在中枢神经系统特定部位微量注射受体药物后进行评估 DA、5-羟色胺和GABAA受体。针对亚型的选定受体药物将是 在每个CNS站点进行测试；VTA、NAC、VP、MPC和DRN。第二，微透析 将被用来评估VTA，NAC，VP， 在操作范式中进行E自我管理期间的MPC和MPC。第三， 加强E在NAC、VP和MPC三个预期地点的作用将 通过使用颅内自我给药(ICSA)进行调查 程序。这一发现将进一步了解 中皮质边缘DA系统在E摄取强化后果中的作用 应该描述某些神经递质受体亚型的重要性 调节这一DA系统，调节乙醇的自我给药。

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.