Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the antipsychotic drug perospirone:: Role of serotonin 5-HT1A receptors
Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the antipsychotic drug perospirone:: Role of serotonin 5-HT1A receptors
复制标题
DOI：
10.1016/j.euroneuro.2007.11.005
复制
发表时间：
2008-06-01
影响因子：
5.6
通讯作者：
Hashimoto, Kenji
中科院分区：
文献类型：
--
作者：
Hagiwara, Hiroko;Fujita, Yuko;Hashimoto, Kenji
越来越多的证据表明，5-羟色胺5-HT 1A受体可能在精神分裂症的病理生理学中发挥作用。本研究旨在探讨具有5-HT 1A受体激动作用的非典型抗精神病药哌罗匹隆对重复给予NMDA受体拮抗剂苯环己哌啶（PCP）后小鼠认知功能障碍的影响。随后亚慢性（14天）给予哌罗匹隆（1.0、3.0或10 mg/kg）以剂量依赖性方式显著减轻PCP（10 mg/kg）诱导的小鼠认知缺陷。与选择性5-HT 1A受体拮抗剂WAY 100635（1.0 mg/kg）合用可显著拮抗哌罗匹隆（10 mg/kg）的作用。此外，5-HT 1A受体激动剂8-OH DPAT（0.25 mg/kg）的低温在PCP处理的小鼠中显著减弱。此外，使用[H-3] WAY 100635进行的受体结合试验显示，PCP处理小鼠海马中的5-HT 1A受体水平显著低于盐水处理小鼠，但额叶皮层中的5-HT 1A受体水平则没有。这些研究结果表明，重复PCP管理改变5-HT 1A受体在小鼠大脑中的功能，和随后的亚慢性给药perospirone改善PCP诱导的认知缺陷通过5-HT 1A受体。因此，perospirone可能是一个潜在的治疗精神分裂症患者的认知功能障碍。(C)2007年Elsevier B. V.和ECNP。All rights reserved.
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.