title: Re-exposure to morphine-associated context facilitated long-term potentiation in the vSUB-NAc glutamatergic pathway via GluN2B-containing receptor activation.
abstract: The glutamatergic projection from the ventral subiculum of the hippocampus (vSUB) to the nucleus accumbens (NAc) shell has been reported to play a key role in drug-related behavior. The GluN2B subunit of N-methyl-D-aspartate receptors (NMDARs) in the NAc can be selectively elevated after the retrieval of drug-conditioned memory. However, whether the increased GluN2B-containing NMDARs (GluN2B-NMDARs) are able to alter the synaptic plasticity of the vSUB-NAc glutamatergic pathway remains unclear. Here, we found that the long-term potentiation (LTP) in the vSUB-NAc pathway was facilitated and the GluN2B subunit protein level was elevated in synaptoneurosomes of the NAc shell, but not in the core, following morphine-induced conditioned place preference (CPP) expression in rats. The facilitated LTP was prevented by the GluN2B-NMDAR antagonist RO25-6981. Also, a neurochemical disconnection following microinjection of RO25-6981 into the NAc shell, plus microinfusion of GABA agonist baclofen and muscimol into the contralateral vSUB prevented the expression of morphine-induced CPP. These findings suggest that the retrieval of drug-associated memory potentiated synaptic plasticity in the vSUB-NAc pathway, which was dependent on GluN2B-NMDAR activation in the NAc shell. These findings provide a new explanation for the mechanisms that underlie the morphine-associated-context memory. The GluN2B-NMDARs may be regarded as a potential target for erasing morphine-related memory.
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education, Beijing, China.|Key Laboratory for Neuroscience, Ministry of National Health and Family Planning Commission, Beijing, China.
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education, Beijing, China.|Key Laboratory for Neuroscience, Ministry of National Health and Family Planning Commission, Beijing, China.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Ping
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education, Beijing, China.|Key Laboratory for Neuroscience, Ministry of National Health and Family Planning Commission, Beijing, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Qi
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education, Beijing, China.|Key Laboratory for Neuroscience, Ministry of National Health and Family Planning Commission, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Shen
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education, Beijing, China.|Key Laboratory for Neuroscience, Ministry of National Health and Family Planning Commission, Beijing, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Sun
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education, Beijing, China.|Key Laboratory for Neuroscience, Ministry of National Health and Family Planning Commission, Beijing, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Sun
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education, Beijing, China.|Key Laboratory for Neuroscience, Ministry of National Health and Family Planning Commission, Beijing, China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Ge
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education, Beijing, China.|Key Laboratory for Neuroscience, Ministry of National Health and Family Planning Commission, Beijing, China.
authors.forename: Guo-Gang
authors.initials: GG
authors.lastname: Xing
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education, Beijing, China.|Key Laboratory for Neuroscience, Ministry of National Health and Family Planning Commission, Beijing, China.
authors.forename: Cai-Lian
authors.initials: CL
authors.lastname: Cui
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D009118:Muscimol; D009020:Morphine; D001418:Baclofen
keywords: Conditioned place preference; NMDA receptors; hippocampus; long-term potentiation; morphine; nucleus accumbens