TS–vMHb–cIPN神经环路在甲基苯丙胺复吸中的作用及机制研究

甲基苯丙胺（Methamphetamine，METH）是常见毒品之一，其高复吸率是戒毒治疗的首要难题，目前，调控METH复吸的神经环路和靶点不明确，导致临床缺乏有效的戒毒干预手段。结合前期的研究工作基础，本项目拟建立小鼠METH自身给药模型，结合光遗传学、膜片钳、钙信号光纤记录、病毒依赖的神经束路追踪等技术，旨在探索：①腹内侧缰核（ventromedial habenula，vMHb）胆碱能神经元集群在METH复吸行为中的作用；②“三角隔核（Triangular septum，TS）–vMHb–脚间核中心部（central core of the IPN，cIPN）”神经环路在METH复吸行为中的作用和关键靶标；③光遗传学调控TS–vMHb–cIPN神经环路对METH复吸行为的影响。本项目的研究成果将有助于阐释调控METH复吸的神经环路和关键靶点，为防治复吸提供新靶标和新策略。

Methamphetamine (METH) has been one of most common abused drugs worldwide. To date, high rate of relapse is the greatest challenges in the treatment of drug addiction (including METH). However, the neural circuits and potential therapeutic targets underlying the development of METH-induced relapse behaviors remain poorly understood. Based on our previous research findings, combining optogenetics, patch clamp, fiber photometry and virus-dependent nervous tract-tracing techniques, METH self-administration (SA) mice model is used to investigate: ① role of cholinergic neurons in ventromedial habenula (vMHb) in METH-induced relapse-like behavior; ② role and targets of ‘triangular septum (TS)–vMHb–central core of the IPN (cIPN)’ circuit in regulating METH-induced relapse-like behavior; ③ effect of optogenetic manipulation of TS–vMHb–cIPN circuit on METH-induced relapse-like behavior. The findings of current study would contribute to understand the neuronal circuits and potential therapeutic targets underlying relapse to METH-seeking behaviors, and be benefit for the research and development of novel therapeutic approaches against relapse to METH.