title: Impaired hippocampal synaptic plasticity and NR2A/2B expression ratio in remifentanil withdrawal rats.
abstract: Remifentanil is a kind of synthetic opioid which has gained wide clinical acceptance by anesthesiologists. In this study, we attempted to test whether withdrawal effects on learning mechanisms can be triggered by repeated low-dose remifentanil treatment. Male Sprague-Dawley (SD) rats were subjected to remifentanil (50μg/kgs.c.) twice per day at 12h intervals for 15 days. When the animals of remifentanil group were withdrawn from remifentanil at 10h after the last injection, changes in open field test, Morris water maze test (MWM) and synaptic efficacy were examined in each group. We demonstrated that repeated exposure to 50μg/kg remifentanil produced enhanced locomotor activity indicating that a remifentanil addiction animal model in rats was established. MWM results showed that exposure to remifentanil had no influence on the spatial cognition. After withdrawal of remifentanil rats showed impaired spatial cognition. In electrophysiology test, remifentanil group rats showed a trend for a rightward shift of input/output relationship and significant deficits in maintenance of STP and LTP. Immunohistochemistry results demonstrated increased NR2A/NR2B ratio that should be included depression of LTP. In the whole-cell patch-clamp recording, after elimination from remifentanil incubation, mEPSC frequency was down regulated in hippocampal CA1 neurons, indicating that basal synaptic transmission were affected by remifentanil withdrawal. Taken together, the current findings demonstrate that the remifentanil withdrawn rats exhibit obvious impairment of hippocampus-dependent memory and synaptic plasticity. Increased hippocampal NR2A/NR2B expression ratio and the changes of basal synaptic transmission may participate in the impairment of LTP.
authors.affiliation: Neurology Department, Tianjin Haihe Hospital, Tianjin 300350, China. Electronic address: wyiyi70@163.com.
authors.forename: Yi-Yi
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Radiology Department, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Shichang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Neurology Department, Tianjing Medical University General Hospital, Tianjin 300052, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Pathology Department, Tianjin Xiqing Hospital, Tianjin 300380, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Physiology and Pathophysiology, Logistics University of Chinese People's Armed Police Force, Tianjin 300309, China.
authors.forename: Yinguo
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000701:Analgesics, Opioid / Q000633:toxicity; D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D000077208:Remifentanil; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D000077208:Remifentanil
keywords: Morris water maze; NR2A/NR2B; Open field test; Remifentanil withdrawal; Synaptic plasticity; mEPSCs