期刊
EUROPEAN NEUROPSYCHOPHARMACOLOGY
卷 18, 期 6, 页码 448-454出版社
ELSEVIER
DOI: 10.1016/j.euroneuro.2007.11.005
关键词
schizophrenia; cognition; 5-HT1A receptors; NMDA receptor; perospirone
Accumulating evidence suggests that the serotonin 5-HT1A receptor may play a role in the pathophysiology of schizophrenia. The present study was undertaken to examine the effects of perospirone, an atypical antipsychotic drug with 5-HT1A receptor agonism, on cognitive deficits in mice after repeated administration of the NMDA receptor antagonist phencyclidine (PCP). Subsequent subchronic (14 days) administration of perospirone (1.0, 3.0, or 10 mg/kg) significantly attenuated PCP (10 mg/kg)-induced cognitive deficits in mice, in a dose-dependent manner. The effects of perospirone (10 mg/kg) were significantly antagonized by co-administration of the selective 5-HT1A receptor antagonist WAY100635 (1.0 mg/kg). Furthermore, hypothermia by the 5-HT1A receptor agonist 8-OH DPAT (0.25 mg/kg) was significantly attenuated in mice treated with PCP. Moreover, a receptor binding assay using [H-3]WAY100635 revealed that levels of 5-HT1A receptors in the hippocampus, but not in the frontal cortex, of PCP-treated mice were significantly tower than those of saline-treated mice. These findings suggest that repeated PCP administration alters 5-HT1A receptor function in the mouse brain, and that subsequent subchronic administration of perospirone ameliorates PCP-induced cognitive deficits via 5-HT1A receptors. Therefore, perospirone could be a potential therapy for the cognitive deficits observed in schizophrenic patients. (C) 2007 Elsevier B.V. and ECNP. All rights reserved.
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