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Pharmacol Biochem Behav. 2014 Sep;124:245-9. doi: 10.1016/j.pbb.2014.06.008. Epub 2014 Jun 20.

Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors.

Author information

1
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan; Qs' Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
2
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
3
Qs' Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
4
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. Electronic address: hashimoto@faculty.chiba-u.jp.

Abstract

Brexpiprazole, a serotonin-dopamine activity modulator, is currently being tested in clinical trials as a new therapy for a number of neuropsychiatric diseases, including schizophrenia and major depressive disorder. Accumulating evidence suggests that 5-hydroxytryptamine (5-HT)1A receptors play a role in cognition. This study was undertaken to examine whether brexpiprazole, a novel drug with 5-HT1A receptor partial agonism, could improve cognitive deficits in mice, induced by repeated administration of the N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine (PCP). Subsequent subchronic (14 days) oral administration of brexpiprazole (0.3, 1, or 3mg/kg/day) significantly attenuated PCP (10mg/kg/day for 10 days)-induced cognitive deficits in mice, in a dose-dependent manner. The effects of brexpiprazole (3mg/kg) were significantly antagonized by co-administration of the selective 5-HT1A receptor antagonist, WAY-100,635 (1.0mg/kg), although WAY-100,635 alone was not effective in this model. These findings suggest that brexpiprazole can ameliorate PCP-induced cognitive deficits in mice via 5-HT1A receptors. Therefore, brexpiprazole could ameliorate cognitive deficits as seen in schizophrenia and other neuropsychiatric diseases.

KEYWORDS:

5-HT(1A) receptors; Brexpiprazole; Cognition; Phencyclidine; Schizophrenia

PMID:
24955861
DOI:
10.1016/j.pbb.2014.06.008
[Indexed for MEDLINE]

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