title: Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors.
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.
authors: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan; Qs' Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
authors: Noriko
authors: N
authors: Yoshimi
authors: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors: Yuko
authors: Y
authors: Fujita
authors: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan; Qs' Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
authors: Yuta
authors: Y
authors: Ohgi
authors: Qs' Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
authors: Takashi
authors: T
authors: Futamura
authors: Qs' Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
authors: Tetsuro
authors: T
authors: Kikuchi
authors: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. Electronic address: hashimoto@faculty.chiba-u.jp.
authors: Kenji
authors: K
authors: Hashimoto
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010622:Phencyclidine / Q000633:toxicity*; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D015363:Quinolones; D011954:Receptors, Dopamine; D013876:Thiophenes; D044282:Receptor, Serotonin, 5-HT1A; C000591922:brexpiprazole; D010622:Phencyclidine
keywords: 5-HT(1A) receptors; Brexpiprazole; Cognition; Phencyclidine; Schizophrenia