Although the use of atypical antipsychotic drugs is successful in the treatment of schizophrenia, they cause complications in the long term use that is mainly weight gain. In this study, circulating levels of hypothalamic neuropeptides/hormones, which are related to appetite regulation / neuropeptide Y (NPY), alpha melanocyte stimulating hormone (&alpha / -MSH), cocaine and amphethamine regulated transcript (CART) and plus leptin in male schizophrenic patients who were treated with an atypical antipsychotic drug, risperidone, which is a serotonin antagonist, for 4 weeks was investigated. Based on the hypothesis that the risperidone treatment might alter the circulating levels of those neuropeptides through the serotonergic antagonism, it results in the weight gain. Leptin plasma levels were increased in the risperidone treated patients accompanying by weight gain vs controls and NPY, &alpha / -MSH, CART levels were decreased in the patients before the treatment but they were not changed after treatment. To determine alterations of those candidate genes mRNA expression levels, male Wistar rats were orally administered with risperidone for 4-weeks. Rat studies show that the mRNA expression and plasma levels of POMC, AgRP, and NPY were decreased but CART mRNA levels were increased while their plasma levels were decreased unexpectedly. In conclusion, the serotonergic antagonism of risperidone on POMC neurons may cause increase in appetite / and hence, increased weight gain and leptin levels, even in a short term trial.

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