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題名 Inhibition of glycogen synthase kinase-3 attenuates psychotomimetic effects of ketamine. 作者 詹銘煥
Chan, Ming-Huan貢獻者 神科所 關鍵詞 GSK-3; NMDA antagonist; Locomotor; Cognition; Prepulse inhibition; Schizophrenia 日期 2012.04 上傳時間 27-May-2014 11:24:46 (UTC+8) 摘要 N-methyl-D-aspartate (NMDA) glutamate receptors mediate fast neurotransmission and regulate synaptic plasticity in the brain. Disruption of NMDA receptor-mediated signaling by noncompetitive antagonists, such as PCP or ketamine, evokes psychotomimetic behaviors, although the cellular mechanisms by which hypofunctional NMDA receptor signaling drives behavioral pathology are still unclear. Activation of glycogen synthase kinase-3 (GSK-3) has been implicated in the cellular neurotoxicity of NMDA receptor antagonists. Accordingly, in the present study we examined the ability of GSK-3 inhibitors, SB216763 and 1-azakenpaullone, to reverse the behavioral aberrations induced by ketamine. Male NMRI mice received intracerebroventricular (i.c.v.) injection of the GSK-3 inhibitors, SB216763 and 1-azakenpaullone, 5 min prior to ketamine administration. Locomotor activity, rotarod performance, prepulse inhibition, novel object recognition, and duration of loss of righting reflex were monitored. GSK-3 inhibitors attenuated ketamine-induced locomotor hyperactivity, motor incoordination, sensorimotor impairment, and cognitive deficits, but did not affect ketamine anesthesia. These data support an important role of GSK-3 in the expression of behavioral aberrations associated with NMDA receptor hypofunction, and suggest that GSK-3 inhibitors may ameliorate certain behavioral and cognitive dysfunctions in patients with schizophrenia. 關聯 Schizophrenia Research, 136(1), 96-103 資料類型 article DOI http://dx.doi.org/10.1007/s11418-011-0623-x dc.contributor 神科所 en_US dc.creator (作者) 詹銘煥 zh_TW dc.creator (作者) Chan, Ming-Huan en_US dc.date (日期) 2012.04 en_US dc.date.accessioned 27-May-2014 11:24:46 (UTC+8) - dc.date.available 27-May-2014 11:24:46 (UTC+8) - dc.date.issued (上傳時間) 27-May-2014 11:24:46 (UTC+8) - dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/66285 - dc.description.abstract (摘要) N-methyl-D-aspartate (NMDA) glutamate receptors mediate fast neurotransmission and regulate synaptic plasticity in the brain. Disruption of NMDA receptor-mediated signaling by noncompetitive antagonists, such as PCP or ketamine, evokes psychotomimetic behaviors, although the cellular mechanisms by which hypofunctional NMDA receptor signaling drives behavioral pathology are still unclear. Activation of glycogen synthase kinase-3 (GSK-3) has been implicated in the cellular neurotoxicity of NMDA receptor antagonists. Accordingly, in the present study we examined the ability of GSK-3 inhibitors, SB216763 and 1-azakenpaullone, to reverse the behavioral aberrations induced by ketamine. Male NMRI mice received intracerebroventricular (i.c.v.) injection of the GSK-3 inhibitors, SB216763 and 1-azakenpaullone, 5 min prior to ketamine administration. Locomotor activity, rotarod performance, prepulse inhibition, novel object recognition, and duration of loss of righting reflex were monitored. GSK-3 inhibitors attenuated ketamine-induced locomotor hyperactivity, motor incoordination, sensorimotor impairment, and cognitive deficits, but did not affect ketamine anesthesia. These data support an important role of GSK-3 in the expression of behavioral aberrations associated with NMDA receptor hypofunction, and suggest that GSK-3 inhibitors may ameliorate certain behavioral and cognitive dysfunctions in patients with schizophrenia. en_US dc.format.extent 561463 bytes - dc.format.mimetype application/pdf - dc.language.iso en_US - dc.relation (關聯) Schizophrenia Research, 136(1), 96-103 en_US dc.subject (關鍵詞) GSK-3; NMDA antagonist; Locomotor; Cognition; Prepulse inhibition; Schizophrenia en_US dc.title (題名) Inhibition of glycogen synthase kinase-3 attenuates psychotomimetic effects of ketamine. en_US dc.type (資料類型) article en dc.identifier.doi (DOI) 10.1007/s11418-011-0623-x - dc.doi.uri (DOI) http://dx.doi.org/10.1007/s11418-011-0623-x -