光干预降低可卡因记忆消退后复吸行为的神经环路机制  

A visual circuit related to the habenula mediates the prevention of cocaine relapse by bright light treatment

作　　者：富昀炜 杨妍 黄鲁 黄晓丹 杨倩 陶倩 吴冀津 苏国辉 林嵩 袁逖飞 任超然 Yunwei Fu;Yan Yang;Lu Huang;Xiaodan Huang;Qian Yang;Qian Tao;Jijin Wu;Kwok-Fai So;Song Lin;Ti-Fei Yuan;Chaoran Ren(Guangdong-Hongkong-Macao Institute of CNS Regeneration,Ministry of Education CNS Regeneration Collaborative Joint Laboratory,Jinan University,Guangzhou 510632,China;Shanghai Key Laboratory of Psychotic Disorders,Brain Health Institute,National Center for Mental Disorders,Shanghai Mental Health Center,Shanghai Jiaotong University School of Medicine,Shanghai 200030,China;Psychology Department,School of Medicine,Jinan University,Guangzhou 510632,China;Physiology Department,School of Medicine,Jinan University,Guangzhou 510632,China;Co-Innovation Center of Neuroregeneration,Nantong University,Nantong 226019,China)

机构地区：[1]Guangdong-Hongkong-Macao Institute of CNS Regeneration,Ministry of Education CNS Regeneration Collaborative Joint Laboratory,Jinan University,Guangzhou 510632,China [2]Shanghai Key Laboratory of Psychotic Disorders,Brain Health Institute,National Center for Mental Disorders,Shanghai Mental Health Center,Shanghai Jiaotong University School of Medicine,Shanghai 200030,China [3]Psychology Department,School of Medicine,Jinan University,Guangzhou 510632,China [4]Physiology Department,School of Medicine,Jinan University,Guangzhou 510632,China [5]Co-Innovation Center of Neuroregeneration,Nantong University,Nantong 226019,China

出　　处：《Science Bulletin》2023年第18期2063-2076,M0004,共15页科学通报（英文版）

基　　金：supported by the STI2030-Major Projects(2021ZD0203100);the National Natural Science Foundation of China(31922030,32171010,31771170,31900720,and 32171009);the Guangdong Basic and Applied Basic Research Foundation(2023B1515040010,2021B1515020035,2019A1515011598,and 2023A1515010478);the Science and Technology Program of Guangdong(2018B030334001);the Science and Technology Program of Guangzhou(202007030012);the Programme of Introducing Talents of Discipline to Universities(B14036).

摘　　要：毒品成瘾已经成为一个严峻挑战,特别是因滥用造成的可卡因高复吸率给社会带来严重负担。尽管我们在神经生物学层面对成瘾的理解取得了显著进展,但仍缺乏有效降低复吸的戒断手段.在这项研究中,我们发现在可卡因戒断期实施亮光干预(BLT)并结合消退训练可防止可卡因驱动的复吸行为,该效应是通过丘脑-外侧核通路所介导。实验证实,在可卡因戒断进程中,外侧核(LHb)被激活,而通过BLT抑制LHb可减少可卡因驱动的复吸行为:本文阐明了BLT的作用是通过激活投射至LHb的腹外侧膝状体和膝状体间小叶(VLGN/IGL)神经元或抑制该通路中突触后LHb神经元实现。此外,BLT可以改善药物戒断引起的负性情绪。本研究结果表明在可卡因戒断期间施加BLT可能成为一种实现药物戒除的有效手段.Despite significant advancements in our understanding of addiction at the neurobiological level,a highly effective extinction procedure for preventing relapse remains elusive.In this study,we report that bright light treatment(BLT)administered during cocaine withdrawal with extinction training prevents cocainedriven reinstatement by acting through the thalamic-habenular pathway.We found that during cocaine withdrawal,the lateral habenula(LHb)was recruited,and inhibition of the LHb via BLT prevented cocaine-driven reinstatement.We also demonstrated that the effects of BLT were mediated by activating LHb-projecting neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet(vLGN/IGL)or by inhibiting postsynaptic LHb neurons.Furthermore,BLT was found to improve aversive emotional states induced by drug withdrawal.Our findings suggest that BLT administered during the cocaine withdrawal may be a promising strategy for achieving drug abstinence.

关 键 词：Light treatment Lateral habenula Cocaine memory Visual circuit 

分 类 号：R749.6[医药卫生—神经病学与精神病学]