Protective effect of aripiprazole against glutamate cytotoxicity in dopaminergic neurons of rat mesencephalic cultures

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.