Effects of repeated risperidone exposure on serotonin receptor subtypes in developing rats

Risperidone is an atypical antipsychotic drug that is widely prescribed to young patients with different psychotic disorders. The long-term effects of this antipsychotic agent on neuronal receptors in developing brain remain unclear and require further investigation. In this study, we examined the effects of long-term treatment of risperidone on two serotonin receptor subtypes in brain regions of juvenile rat. Levels of 5-HT1A and 5-HT2A receptors in forebrain regions of juvenile rats were quantified after 3 weeks of treatment with three different doses of risperidone (0.3, 1.0 and 3.0 mg/kg). Findings were compared to previously reported changes in 5-HT receptors after risperidone treatment (3.0 mg/kg) in adult rat brain. The three doses of risperidone selectively and dose-dependently increased levels of 5-HT1A receptors in medial–prefrontal and dorsolateral–frontal cortices of juvenile animals. The higher doses (1.0 and 3.0 mg/kg) of risperidone also increased 5-HT1A receptor binding in hippocampal CA1 region of juvenile but not adult rats. In contrast, the three doses of risperidone significantly reduced 5-HT2A labeling in medial–prefrontal and dorsolateral–frontal cortices in juvenile as well as in adult animals in an equipotent fashion. 5-HT1A and 5-HT2A receptors in other forebrain regions were not altered by repeated risperidone treatment. These findings indicate that there are differential effects of risperidone on 5-HT1A and 5-HT2A receptors in juvenile animals, and that the 5-HT system in developing animals is more sensitive than adults to the long-term effects of risperidone.