Glutamatergic neurons in ventral pallidum modulate heroin addiction via epithalamic innervation in rats  

作　　者：Ruo-song Chen Jing Liu Yu-jun Wang Kuan Ning Jing-gen Liu Zhi-qiang Liu 

机构地区：[1]Shanghai Key Laboratory of Maternal Fetal Medicine,Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology,Department of Anesthesiology,Shanghai First Maternity and Infant Hospital,School of Medicine,Tongji University,Shanghai,201204,China [2]Center for Neurological and Psychiatric Research and Drug Discovery,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [3]State Key Laboratory of Natural Medicines,School of Biopharmacy,China Pharmaceutical University,Nanjing,211198,China [4]School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing,210023,China [5]Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province,School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou,310053,China

出　　处：《Acta Pharmacologica Sinica》2024年第5期945-958,共14页中国药理学报（英文版）

基　　金：supported by the Major Project of the Science and Technology Innovation 2030 of China(2021ZD0203500,STI2030-Major Projects 2021ZD0202900);National Natural Science Foundation of China(82030112,81773710,82371533,82301677);Science and Technology Commission of Shanghai Municipality(20ZR1468200);Natural Science Foundation of Shanghai(22ZR1449300);Program of Shanghai Academic/Technology Research Leader(22XD1402400);Shenzhen-Hong Kong Institute of Brain Science—Shenzhen Fundamental Research Institutions(NYKFKT2019015).

摘　　要：Glutamatergic neurons in ventral pallidum(VP^(Glu))were recently reported to mediate motivational and emotional behavior,but its role in opioid addiction still remains to be elucidated.In this study we investigated the function of VP^(Glu) in the context-dependent heroin taking and seeking behavior in male rats under the ABA renewal paradigm.By use of cell-type-specific fiber photometry,we showed that the calcium activity of VP^(Glu) were inhibited during heroin self-administration and context-induced relapse,but activated after extinction in a new context.The drug seeking behavior was accompanied by the decreased calcium signal of VP^(Glu).Chemogenetic manipulation of VP^(Glu) bidirectionally regulated heroin taking and seeking behavior.Anterograde tracing showed that the lateral habenula,one of the epithalamic structures,was the major output region of VP^(Glu),and its neuronal activity was consistent with VP^(Glu) in different phases of heroin addiction and contributed to the motivation for heroin.VP^(Glu) axon terminals in LHb exhibited dynamic activity in different phases of heroin addiction.Activation of VP^(Glu)-LHb circuit reduced heroin seeking behavior during context-induced relapse.Furthermore,the balance of excitation/inhibition from VP to LHb was shifted to enhanced glutamate transmission after extinction of heroin seeking motivation.Overall,the present study demonstrated that the activity of VP^(Glu) was involved in the regulation of heroin addiction and identified the VP^(Glu)-LHb pathway as a potential intervention to reduce heroin seeking motivation.

关 键 词：heroin addiction drug taking and seeking context-induced relapse ventral pallidum lateral habenula glutamatergic neurons 

分 类 号：R99[医药卫生—毒理学]