GABAergic alterations in the BNST to VTA circuit following morphine withdrawal

点击翻译按钮获取中文摘要

Project Summary/Abstract The opioid epidemic is a continuously growing problem in the United States and across the world. It has profound personal, social, and economic consequences. Opioid use can become Opioid Use Disorder (OUD) in many individuals. OUD consists of several stages, one of which is a highly dysphoric withdrawal syndrome known as Opioid Withdrawal Syndrome (OWS). The withdrawal symptoms, including sleep dysregulation, and fear of those symptoms often contributes drastically to relapse. We do not currently understand all of the neurobiological mechanisms underlying opioid withdrawal, nor how particular circuits are modified by opioid withdrawal. It is well known, however, that two brain regions, the bed nucleus of the stria terminalis (BNST) and the ventral tegmental area (VTA), are involved in some capacity. In the two aims of this proposal, the experiments will help to understand how the pathway between these two regions is modified by opioid withdrawal. Our preliminary data shows that the GABAergic neurons in the BNST are altered by withdrawal. BNSTGABA neurons make up the bulk of the BNST neurons projecting to the VTA, where they synapse onto VTAGABA neurons, and have been implicated in positive reinforcement. This project utilizes viral-manipulations, behavioral studies, and electrophysiological examinations to carefully and specifically determine the effects of withdrawal in the BNST. In the second portion of this proposal, the experiments are focused on the output of this pathway in the VTA as well as a knockdown of this pathway to elucidate the role of this pathway in controlling behavior.