Developmental effects of antipsychotic drugs on serotonin receptor subtypes.

Antipsychotic medications are increasingly prescribed to pediatric and adolescent patients with psychotic diseases in spite of limited knowledge on the long-term effects of dissimilar antipsychotic drugs on developing brain. In this study, we quantified the levels of two major serotonin 5-HT , and 5-HT receptors in brain regions of developing rats after 3 weeks of treatment with typical (fluphenazine) and atypical (clozapine and olanzapine) antipsychotics, and compared to similarly treated adult rats treated with olanzapine, risperidone, and quetiapine examined in previous studies. Fluphenazine, clozapine, and olanzapine all increased 5-HT receptors in medial prefrontal cortex (MPC) and dorsolateral frontal cortex (DFC) of juvenile and adult rats. Clozapine and olanzapine also increased 5-HT labeling in hippocampal CA and CA regions of juvenile but not adult animals. Repeated treatments with clozapine and olanzapine, but not fluphenazine, decreased 5-HT receptors in MPC and DFC in developing and mature animals. In addition, both clozapine and olanzapine selectively reduced 5-HT labeling in hippocampal CA and CA regions of juvenile animals. These findings suggest that forebrain 5-HT receptor subtypes in juvenile animals are more sensitive than adults to the long-term effects of antipsychotic drugs, which may account for differences in clinical effects of antipsychotic drugs between young vs. adult psychiatric patients.