title: Therapeutic effects of metabotropic glutamate receptor 5 positive allosteric modulator CDPPB on phencyclidine-induced cognitive deficits in mice.
abstract: This study was undertaken to examine the effects of CDPPB (3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide), a positive allosteric modulator (PAM) of metabotropic glutamate receptor 5 (mGlu₅), on cognitive deficits in mice after repeated administration of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP). In the novel object recognition test, PCP (10 mg/kg/day for 10 days)-induced cognitive deficits in mice were not improved by a single administration of CDPPB (10 mg/kg/day). However, PCP (10 mg/kg/day for 10 days)-induced cognitive deficits in mice were significantly improved by subsequent subchronic (14 days) administration of CDPPB (10 mg/kg/day), but not of CDPPB (1.0 mg/kg/day). This study suggests that PCP-induced cognitive deficits in mice are improved by subsequent subchronic administration of CDPPB. Therefore, mGlu₅ PAMs would be potential therapeutic drugs for cognitive deficits in schizophrenia.
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1, Inohana, Chiba 260-8670, Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Horio
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000819:agonists; D009474:Neurons / Q000187:drug effects; D010622:Phencyclidine; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D064529:Receptor, Metabotropic Glutamate 5 / Q000819:agonists*; D021641:Recognition, Psychology / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: C494553:3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide; D014150:Antipsychotic Agents; D001549:Benzamides; D018690:Excitatory Amino Acid Agonists; C578936:Grm5 protein, mouse; D009419:Nerve Tissue Proteins; D011720:Pyrazoles; D064529:Receptor, Metabotropic Glutamate 5; D010622:Phencyclidine