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

• Published in: Pharmacology, biochemistry and behavior Vol. 124; pp. 245 - 249
• Main Authors: Yoshimi, Noriko, Fujita, Yuko, Ohgi, Yuta, Futamura, Takashi, Kikuchi, Tetsuro, Hashimoto, Kenji
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2014
• Subjects: 5-HT1A receptors; Animals; Brexpiprazole; Cognition; Cognition Disorders - chemically induced; Cognition Disorders - drug therapy; Male; Mice; Mice, Inbred ICR; Phencyclidine; Phencyclidine - toxicity; Quinolones - pharmacology; Quinolones - therapeutic use; Receptor, Serotonin, 5-HT1A - drug effects; Receptors, Dopamine - drug effects; Schizophrenia; Thiophenes - pharmacology; Thiophenes - therapeutic use; Brexpiprazole; Schizophrenia; Cognition; Phencyclidine; 5-HT1A receptors; 5-HT(1A) receptors
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2014.06.008

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 (14days) oral administration of brexpiprazole (0.3, 1, or 3mg/kg/day) significantly attenuated PCP (10mg/kg/day for 10days)-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. •Brexpiprazole is a novel antipsychotic drug with 5-HT1A agonism.•Brexpiprazole improved phencyclidine-induced cognitive deficits in mice.•WAY-100,635, a 5-HT1A receptor antagonist, blocked the effect of brexpiprazole.•Brexpiprazole could ameliorate cognitive deficits in schizophrenia.