Effects of an atypical antipsychotic drug olanzapine on the expression of neuronal nitric oxide synthase in a dopaminergic cell line, SH-SY5Y

초록

Atypical antipsychotic agents like clozapine (CLZ) and olanzapine (OLZ) produce fewer extrapyramidal side effects and are effective in alleviating the negative symptoms of schizophrenia. However, the drugs can cause weight gain possibly by antagonizing histamine and 5-hydroxytryptamine (5-HT; serotonin) receptors and increaing leptin levels. Since NO released by neuronal nitric oxide synthase (nNOS) plays an important role in neurotransmission in brain, we investigated the effects of OLZ on the expression and activity of the nNOS in a dopaminergic neuronal cell line, SH-SY5Y. The treatment of cells with OLZ caused a transient increases in nNOS expression and activity in a concentration-dependent manner, which was prevented by concomitant treatment with selective inhibitor of PKA, PKC or CaM K-II. These results suggest that OLZ administration in schizophrenia patients can transiently increase nNOS expression in brain via protein kinase-mediated mechanisms, which may contribute to drug-toxicity in brain with transient increase in NO level in brain.