ALCOHOL REGULATION OF KAPPA OPIOID RECEPTOR SYSTEMS IN THE EXTENDED AMYGDALA

描述（由申请人提供）：酒精使用障碍是一个主要的公共卫生问题，迄今为止，没有全面的治疗或干预。终纹床核（BNST）参与整合皮质和皮质下输入以协调行为反应，并与酒精使用和滥用以及压力相关行为有关。κ阿片受体（KOR）已被证明在BNST中改变神经递质信号传导[1]，尽管其对阿片能传递的影响尚未被证实。 被阐明。该项目的目标是对KORs在BNST中的神经递质信号传导中的作用进行彻底的调查和表征，以及这种连接如何被酒精依赖模型改变。为了完成第一个目标，我将使用切片电生理学来评估BNST中的多巴胺能KOR的功能、信号传导和位点。为了完成第二个目标，我将使用光遗传学，慢性间歇性乙醇暴露和切片电生理学的组合来评估KOR如何调节乙醇暴露前后BNST的通路特异性输入。因此，该提案将使用创新方法的组合，以提供表征BNST中KOR对神经递质传递的调制的全面和收敛的证据。

DESCRIPTION (provided by applicant): Alcohol use disorders represent a major public health problem, and to date, no comprehensive treatment or intervention is available. The Bed Nucleus of the Stria Terminalis (BNST) is involved in integrating cortical and subcortical inputs to orchestrate behavioral responses, and has been implicated in alcohol use and abuse, as well as stress related behaviors. The kappa opioid receptor (KOR) has been demonstrated in the BNST to alter neurotransmitter signaling [1], though its effect on glutamatergic transmission has yet to be elucidated. The goals of this project are to conduct a thorough investigation and characterization into the role of KORs on glutamatergic signaling in the BNST, and how this connection is altered by a model of alcohol dependence. To complete the first aim, I will use slice electrophysiology to evaluate the function, signaling, and locus of glutamatergic KORs in the BNST. To complete this second aim, I will use a combination of optogenetics, chronic-intermittent ethanol exposure, and slice electrophysiology to assess how KORs modulate pathways- specific inputs to the BNST both before and after ethanol exposure. Thus, this proposal will use a combination of innovative approaches to provide thorough and convergent evidence characterizing KOR modulation of glutamatergic transmission in the BNST.