6/8: INIA Stress and Chronic Alcohol Interactions: Deconstructing the role of extended amygdala circuits in stress regulated alcohol drinking

越来越多的文献表明，长期饮酒会导致中枢应激的招募 关键大脑中的促肾上腺皮质激素释放因子(CRF)和强啡肽(Dyn)等系统 终纹床核(BNST)和中央核的环路 杏仁核(CEA)，导致功能连接和病理行为改变。然而， 我们对促成这一现象的更广泛的电路机制的了解仍然存在差距。 行为失控。我们的目标是确定酒精在压力回路中诱导的适应 提供基于电路的模板，用于治疗酒精使用障碍和并存疾病 条件。在之前的资金支持期间，我们发现BNST中CRF神经元的激活 因过度饮酒而被要求。在这里，我们建议确定 间歇性酒精暴露和应激对大鼠脑内神经元亚群可塑性的影响 BNST和CEA。需要检验的中心假设是，反复饮酒会导致 应激导致延展杏仁核CRF和Dyn募集增加，驾驶 病态行为。

A growing literature indicates that chronic alcohol exposure leads to recruitment of central stress systems, such as corticotrophin releasing factor (CRF) and Dynorphin (DYN), in key brain circuits including the bed nucleus of the stria terminalis (BNST) and Central nucleus of the amygdala (CeA), leading to altered functional connectivity and pathological behavior. However, there remains a gap in our knowledge of the broader circuit mechanisms that contribute to this dysregulated behavior. Our goal is to identify alcohol induced adaptations in stress circuitry to provide a circuit based template for treatment of alcohol use disorders and co-morbid conditions. In the previous funding period, we found that activation of CRF neurons in the BNST are required for excessive alcohol consumption. Here, we propose to determine the impact of intermittent alcohol exposure and stress on plasticity in subpopulations of neurons in both the BNST and the CeA. The central hypothesis to be tested is that repeated alcohol exposure leads to increased stress induced recruitment of extended amygdala CRF and DYN, driving pathological behavior.