title: Clozapine prevents a decrease in neurogenesis in mice repeatedly treated with phencyclidine.
abstract: It has recently been suggested that neurogenesis in the dentate gyrus is decreased in schizophrenia and this phenomenon may contribute to the pathogenesis of the disorder. Since repeated administration of psychostimulants such as phencyclidine (PCP), MK-801, and methamphetamine (METH) induces schizophrenia-like behavioral changes in animals, we investigated whether repeated administration of these psychostimulants affects neurogenesis in the dentate gyrus of mice. Newborn cells were labeled by bromodeoxyuridine (BrdU) and detected by immunohistochemistry. Repeated administration of PCP and MK-801, but not METH, resulted in a decrease in the number of BrdU-labeled cells in the dentate gyrus. PCP-induced decrease in the number of BrdU-labeled cells was negated by co-administration of clozapine, but not haloperidol, although repeated antipsychotics treatment by themselves had no effect. Furthermore, co-administration of D-serine and glycine, but not L-serine, inhibited the PCP-induced decrease in the number of BrdU-labeled cells. These results suggest that chronic dysfunction of NMDA receptors causes a decrease in neurogenesis in the dentate gyrus.
authors.affiliation: Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Maeda
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugino
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hirose
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D003024:Clozapine / Q000008:administration & dosage*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D010622:Phencyclidine / Q000008:administration & dosage*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010622:Phencyclidine; D003024:Clozapine