Protective effect of aripiprazole against glutamate cytotoxicity in dopaminergic neurons of rat mesencephalic cultures |
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| Authors: | Takaaki Matsuo Yasuhiko Izumi Toshiaki Kume Yuki Takada-Takatori Hideyuki Sawada Akinori Akaike |
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| Affiliation: | 1. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan;2. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women''s College, Kodo, Kyotanabe, Kyoto 610-0395, Japan;3. Department of Neurology and Clinical Research Center, Center for Neurological Diseases, Utano National Hospital, 8 Ondoyamacho, Narutaki, Ukyo-ku, Kyoto 616-8255, Japan |
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| Abstract: | Aripiprazole, a dopamine D2 receptor partial agonist, is used to treat schizophrenia. Although aripiprazole has been reported to protect non-dopaminergic neurons, its effect on dopaminergic neurons has yet to be investigated. In the present study, we examined whether aripiprazole protected dopaminergic neurons against glutamate-induced cytotoxicity in rat mesencephalic cultures. Pretreatment with aripiprazole protected dopaminergic neurons in a concentration-dependent manner. The neuroprotective effect was not attenuated by sulpiride, a dopamine D2 receptor antagonist, suggesting that the effect is independent of dopamine D2 receptors. Aripiprazole reduced intracellular dopamine content in a concentration-dependent manner. In addition, its neuroprotective effect was partially inhibited when dopamine was added. These results suggest that aripiprazole protects dopaminergic neurons against glutamate cytotoxicity partly by reducing intracellular dopamine content. |
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| Keywords: | Aripiprazole Dopamine Glutamate cytotoxicity Intracellular dopamine content Neuroprotective effect |
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