Activation of mesocorticolimbic dopamine projections initiates cue-induced reinstatement of reward seeking in mice  

作　　者：Man-yi Jing Xiao-yan Ding Xiao Han Tai-yun Zhao Min-min Luo Ning Wu Jin Li Rui Song 

机构地区：[1]tate Key Laboratory of Toxicology and Medical Countermeasures,Beijing Key Laboratory of Neuropsychopharmacology,Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China [2]Nanjing University of Chinese Medicine,Nanjing 210029,China [3]National Institute of Biological Sciences,Beijing 102206,China

出　　处：《Acta Pharmacologica Sinica》2022年第9期2276-2288,共13页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(81573405 and U1502225);Natural Science Foundation of Beijing(7212159);National Key R&D Program of China(2016YFC0800907);National Key R&D Program of China(2017YFC131040);Medical Innovation Program(16CXZ033);Beijing Nova Program(xx2014A014).

摘　　要：Drug addiction is characterized by relapse when addicts are re-exposed to drug-associated environmental cues,but the neural mechanisms underlying cue-induced relapse are unclear.In the present study we investigated the role of a specific dopaminergic(DA)pathway from ventral tegmental area(VTA)to nucleus accumbens core(NAcore)in mouse cue-induced relapse.Optical intracranial self-stimulation(oICSS)was established in DAT-Cre transgenic mice.We showed that optogenetic excitation of DA neurons in the VTA or their projection terminals in NAcore,NAshell or infralimbic prefrontal cortex(PFC-IL)was rewarding.Furthermore,activation of the VTA-NAcore pathway alone was sufficient and necessary to induce reinstatement of oICSS.In cocaine self-administration model,cocaine-associated cues activated VTA DA neurons as assessed by intracellular GCaMP signals.Cue-induced reinstatement of cocaine-seeking was triggered by optogenetic stimulation of the VTA-NAcore pathway,and inhibited by chemogenetic inhibition of this pathway.Together,these results demonstrate that cue-induced reinstatement of reward seeking is in part mediated by activation of the VTA-NAcore DA pathway.

关 键 词：drug addiction DOPAMINE ventral tegmental area nucleus accumbens medial prefrontal cortex optogenetic optical intracranial self-stimulation cocaine self-administration 

分 类 号：R589.2[医药卫生—内分泌]