Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6265646 | Brain Research | 2009 | 8 Pages |
This study was undertaken to examine the effects of two acetylcholinesterase inhibitors (donepezil and physostigmine) on cognitive deficits in mice after repeated administration of the NMDA receptor antagonist phencyclidine (PCP). In the novel object recognition test, PCP (10Â mg/kg/day for 10Â days)-induced cognitive deficits were significantly improved by subsequent subchronic (14Â days) administration of donepezil (1.0Â mg/kg/day), but not donepezil (0.1Â mg/kg/day). Furthermore, the effect of donepezil (1.0Â mg/kg/day) on PCP-induced cognitive deficits was significantly antagonized by co-administration of the selective sigma-1 receptor antagonist NE-100 (1.0Â mg/kg/day), suggesting the role of sigma-1 receptors in the active mechanisms of donepezil. In contrast, PCP-induced cognitive deficits were not improved by subsequent subchronic (14Â days) administration of physostigmine (0.25Â mg/kg/day). Moreover, repeated administration of PCP significantly caused the reduction of sigma-1 receptors in the hippocampus. The present study suggests that agonistic activity of donepezil at sigma-1 receptors plays a role in the active mechanisms of donepezil on PCP-induced cognitive deficits in mice. Therefore, it is likely that donepezil would be potential therapeutic drugs for the treatment of the cognitive deficits in schizophrenia.