title: Improvement of dizocilpine-induced social recognition deficits in mice by brexpiprazole, a novel serotonin-dopamine activity modulator.
abstract: Cognitive impairment, including impaired social cognition, is largely responsible for the deterioration in social life suffered by patients with psychiatric disorders, such as schizophrenia and major depressive disorder (MDD). Brexpiprazole (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one), a novel serotonin-dopamine activity modulator, was developed to offer efficacious and tolerable therapy for different psychiatric disorders, including schizophrenia and adjunctive treatment of MDD. In this study, we investigated whether brexpiprazole could improve social recognition deficits (one of social cognition deficits) in mice, after administration of the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine). Dosing with dizocilpine (0.1mg/kg) induced significant impairment of social recognition in mice. Brexpiprazole (0.01, 0.03, 0.1mg/kg, p.o.) significantly ameliorated dizocilpine-induced social recognition deficits, without sedation or a reduction of exploratory behavior. In addition, brexpiprazole alone had no effect on social recognition in untreated control mice. By contrast, neither risperidone (0.03mg/kg, p.o.) nor olanzapine (0.03mg/kg, p.o.) altered dizocilpine-induced social recognition deficits. Finally, the effect of brexpiprazole on dizocilpine-induced social recognition deficits was antagonized by WAY-100,635, a selective serotonin 5-HT1A antagonist. These results suggest that brexpiprazole could improve dizocilpine-induced social recognition deficits via 5-HT1A receptor activation in mice. Therefore, brexpiprazole may confer a beneficial effect on social cognition deficits in patients with psychiatric disorders.
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan; Qs׳ Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yoshimi
authors.affiliation: Qs׳ Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Futamura
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. Electronic address: hashimoto@faculty.chiba-u.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D016291:Dizocilpine Maleate / Q000633:toxicity; D015259:Dopamine Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015363:Quinolones / Q000627:therapeutic use*; D021641:Recognition, Psychology / Q000187:drug effects; D018490:Serotonin Agents / Q000627:therapeutic use*; D012919:Social Behavior; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D015363:Quinolones; D018490:Serotonin Agents; D013876:Thiophenes; C000591922:brexpiprazole; D016291:Dizocilpine Maleate
keywords: 5-HT(1A) receptor; Antipsychotic drug; Brexpiprazole; Dizocilpine; Social recognition