title: Glutamatergic Projections from the Entorhinal Cortex to Dorsal Dentate Gyrus Mediate Context-Induced Reinstatement of Heroin Seeking.
abstract: Reexposure to the context associated with heroin intake provokes relapse to drug taking after abstinence. The dorsal dentate gyrus (dDG) and entorhinal cortex (EC) have been implicated in contextual memory processing, but the underlying circuit mechanisms in context-induced relapse remain poorly understood. In this study, using a self-administration rat model, we found that activation and synaptic transmission of glutamatergic projections from the EC to the upper blade of dentate gyrus (dDGub) were significantly enhanced during context-induced reinstatement of heroin seeking. This effect was associated with increased of phosphorylation of GluN2B-containing NMDA receptors (GluN2B) at Y1472, ratio of GluN2B membrane/total protein levels, and expression of downstream extracellular signal-regulated kinase-1/2 (ERK1/2) in the dDG region. Furthermore, DREADD-mediated specific inactivation of the EC-dDG pathway or disconnection of the pathway with local postsynaptic GluN2B-ERK1/2 signaling both decreased context-induced reinstatement of heroin seeking. These experimental manipulations had no effect on saccharin-reinforced responding and general locomotor activity in rats. Our results indicate that the EC-dDG pathway mediates context-induced reinstatement of heroin seeking, via the activation of postsynaptic GluN2B-ERK1/2 signaling in the dDG.
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of the Ministry of Education and National Health and Family Planning Commission, Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Ge
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of the Ministry of Education and National Health and Family Planning Commission, Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of the Ministry of Education and National Health and Family Planning Commission, Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Cailian
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of the Ministry of Education and National Health and Family Planning Commission, Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of the Ministry of Education and National Health and Family Planning Commission, Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of the Ministry of Education and National Health and Family Planning Commission, Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Yaoying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of the Ministry of Education and National Health and Family Planning Commission, Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of the Ministry of Education and National Health and Family Planning Commission, Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Haolin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of the Ministry of Education and National Health and Family Planning Commission, Neuroscience Research Institute, Peking University, Beijing, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Sun
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D058999:Drug-Seeking Behavior / Q000502:physiology*; D018728:Entorhinal Cortex / Q000378:metabolism* / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism*; D003932:Heroin / Q000008:administration & dosage; D006556:Heroin Dependence / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012439:Saccharin / Q000008:administration & dosage; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D003932:Heroin; D012439:Saccharin