Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8351107 | Pharmacology Biochemistry and Behavior | 2014 | 5 Pages |
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 (14Â days) oral administration of brexpiprazole (0.3, 1, or 3Â mg/kg/day) significantly attenuated PCP (10Â mg/kg/day for 10Â days)-induced cognitive deficits in mice, in a dose-dependent manner. The effects of brexpiprazole (3Â mg/kg) were significantly antagonized by co-administration of the selective 5-HT1A receptor antagonist, WAY-100,635 (1.0Â mg/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.
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Authors
Noriko Yoshimi, Yuko Fujita, Yuta Ohgi, Takashi Futamura, Tetsuro Kikuchi, Kenji Hashimoto,