Clozapine prevents a decrease in neurogenesis in mice repeatedly treated with phencyclidine

Kenji Maeda, Haruhiko Sugino, Tsuyoshi Hirose, Hisashi Kitagawa, Taku Nagai, Hiroyuki Mizoguchi, Kazuhiro Takuma, Kiyofumi Yamada

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)299-308
Number of pages10
JournalJournal of Pharmacological Sciences
Volume103
Issue number3
DOIs
Publication statusPublished - 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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