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重大的公共卫生问题，迄今为止，没有全面的治疗或干预措施。终纹床核（BNST）参与整合皮层和皮层下输入以协调行为反应，并与酒精使用和滥用以及与压力相关的行为有关。kappa阿片受体（KOR）在BNST中已被证明可以改变神经递质信号[1]，尽管其对谷氨酸能传递的影响尚未得到证实

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.