Protective effect of aripiprazole against glutamate cytotoxicity in dopaminergic neurons of rat mesencephalic cultures.
Aripiprazole, a dopamine D(2) 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 D(2) receptor antagonist, suggesting that the effect is independent of dopamine D(2) 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.
Matsuo
Takaaki
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Izumi
Yasuhiko
Y
Kume
Toshiaki
T
Takada-Takatori
Yuki
Y
Sawada
Hideyuki
H
Akaike
Akinori
A
D000818:Animals; D000068180:Aripiprazole; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018698:Glutamic Acid / Q000633:toxicity*; D008636:Mesencephalon / Q000166:cytology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D018696:Neuroprotective Agents; D010879:Piperazines; D015363:Quinolones; D018698:Glutamic Acid; D000068180:Aripiprazole; C043425:vanoxerine; D004298:Dopamine