Therapeutic effects of metabotropic glutamate receptor 5 positive allosteric modulator CDPPB on phencyclidine-induced cognitive deficits in mice
Therapeutic effects of metabotropic glutamate receptor 5 positive allosteric modulator CDPPB on phencyclidine-induced cognitive deficits in mice
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DOI：
10.1111/j.1472-8206.2012.01045.x
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发表时间：
2013-10-01
影响因子：
2.9
通讯作者：
Hashimoto, Kenji
中科院分区：
文献类型：
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作者：
Horio, Mao;Fujita, Yuko;Hashimoto, Kenji
本研究旨在研究代谢性谷氨酸受体5 （mGlu(5)）的阳性变构调节剂（PAM） CDPPB(3-氰- n -（1,3-二苯基- 1h -吡唑-5-酰基）苯甲酰胺（CDPPB）对反复给药n -甲基-d -天冬氨酸（NMDA）受体拮抗剂苯环利定（PCP）后小鼠认知障碍的影响。在新的目标识别测试中，单次给予CDPPB （10mg/kg/天）并没有改善PCP （10mg/kg/天）诱导的小鼠认知缺陷。然而，随后的亚慢性（14天）给药CDPPB （10mg/kg/天）可显著改善PCP （10mg/kg/天，连续10天）诱导的小鼠认知缺陷，但CDPPB （1.0mg/kg/天）没有改善。该研究表明，随后亚慢性给药CDPPB可改善pcp诱导的小鼠认知缺陷。因此，mGlu(5) PAMs可能是治疗精神分裂症认知缺陷的潜在药物。
This study was undertaken to examine the effects of CDPPB (3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide), a positive allosteric modulator (PAM) of metabotropic glutamate receptor 5 (mGlu(5)), on cognitive deficits in mice after repeated administration of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP). In the novel object recognition test, PCP (10mg/kg/day for 10days)-induced cognitive deficits in mice were not improved by a single administration of CDPPB (10mg/kg/day). However, PCP (10mg/kg/day for 10days)-induced cognitive deficits in mice were significantly improved by subsequent subchronic (14days) administration of CDPPB (10mg/kg/day), but not of CDPPB (1.0mg/kg/day). This study suggests that PCP-induced cognitive deficits in mice are improved by subsequent subchronic administration of CDPPB. Therefore, mGlu(5) PAMs would be potential therapeutic drugs for cognitive deficits in schizophrenia.