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https://nccur.lib.nccu.edu.tw/handle/140.119/65231
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| Title: | Inhibition of glycogen synthase kinase-3 attenuates psychotomimetic effects of ketamine |
| Authors: | Chan, Ming-Huan;Chiu, Pao-Hsiang;Lin, Chia-Yu;Chen, Hwei-Hsien
詹銘煥 |
| Contributors: | 神科所 |
| Keywords: | GSK-3;NMDA antagonist;Locomotor;Cognition;Prepulse inhibition;Schizophrenia |
| Date: | 2012.04 |
| Issue Date: | 2014-04-09 17:17:54 (UTC+8) |
| Abstract: | 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. |
| Relation: | Schizophrenia research,136(1), 96-103 |
| Source URI: | http://dx.doi.org/10.1016/j.schres.2012.01.024 |
| Data Type: | article |
| Appears in Collections: | [神經科學研究所] 期刊論文
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Files in This Item:
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Size | Format | |
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| 96-103.pdf | | 548Kb | Adobe PDF2 | 1107 | View/Open |
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