Clozapine Prevents a Decrease in Neurogenesis in Mice Repeatedly Treated With Phencyclidine
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 schizo...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2007-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319343087 |
| _version_ | 1818201560220434432 |
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| author | Kenji Maeda Haruhiko Sugino Tsuyoshi Hirose Hisashi Kitagawa Taku Nagai Hiroyuki Mizoguchi Kazuhiro Takuma Kiyofumi Yamada |
| author_facet | Kenji Maeda Haruhiko Sugino Tsuyoshi Hirose Hisashi Kitagawa Taku Nagai Hiroyuki Mizoguchi Kazuhiro Takuma Kiyofumi Yamada |
| author_sort | Kenji Maeda |
| collection | DOAJ |
| description | 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. Keywords:: neurogenesis, phencyclidine, methamphetamine, clozapine, D-serine |
| first_indexed | 2024-12-12T02:55:30Z |
| format | Article |
| id | doaj.art-3830021688564cc9abbfc2a17eca2b14 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-12T02:55:30Z |
| publishDate | 2007-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-3830021688564cc9abbfc2a17eca2b142022-12-22T00:40:47ZengElsevierJournal of Pharmacological Sciences1347-86132007-01-011033299308Clozapine Prevents a Decrease in Neurogenesis in Mice Repeatedly Treated With PhencyclidineKenji Maeda0Haruhiko Sugino1Tsuyoshi Hirose2Hisashi Kitagawa3Taku Nagai4Hiroyuki Mizoguchi5Kazuhiro Takuma6Kiyofumi Yamada7Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, Japan; Second Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Tokushima 771-0192, JapanSecond Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Tokushima 771-0192, JapanSecond Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Tokushima 771-0192, JapanSecond Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Tokushima 771-0192, JapanLaboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, JapanLaboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, JapanLaboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, JapanLaboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, Japan; Corresponding author. kyamada@p.kanazawa-u.ac.jpIt 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. Keywords:: neurogenesis, phencyclidine, methamphetamine, clozapine, D-serinehttp://www.sciencedirect.com/science/article/pii/S1347861319343087 |
| spellingShingle | Kenji Maeda Haruhiko Sugino Tsuyoshi Hirose Hisashi Kitagawa Taku Nagai Hiroyuki Mizoguchi Kazuhiro Takuma Kiyofumi Yamada Clozapine Prevents a Decrease in Neurogenesis in Mice Repeatedly Treated With Phencyclidine Journal of Pharmacological Sciences |
| title | Clozapine Prevents a Decrease in Neurogenesis in Mice Repeatedly Treated With Phencyclidine |
| title_full | Clozapine Prevents a Decrease in Neurogenesis in Mice Repeatedly Treated With Phencyclidine |
| title_fullStr | Clozapine Prevents a Decrease in Neurogenesis in Mice Repeatedly Treated With Phencyclidine |
| title_full_unstemmed | Clozapine Prevents a Decrease in Neurogenesis in Mice Repeatedly Treated With Phencyclidine |
| title_short | Clozapine Prevents a Decrease in Neurogenesis in Mice Repeatedly Treated With Phencyclidine |
| title_sort | clozapine prevents a decrease in neurogenesis in mice repeatedly treated with phencyclidine |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319343087 |
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