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

研究成果: Article査読

60 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)299-308
ページ数10
ジャーナルJournal of Pharmacological Sciences
103
3
DOI
出版ステータスPublished - 2007
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 薬理学

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