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_1A , and 5-HT_2A 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_1A receptors in medial prefrontal cortex (MPC) and dorsolateral frontal cortex (DFC) of juvenile and adult rats. Clozapine and olanzapine also increased 5-HT_1A labeling in hippocampal CA₁ and CA₃ regions of juvenile but not adult animals. Repeated treatments with clozapine and olanzapine, but not fluphenazine, decreased 5-HT_2A receptors in MPC and DFC in developing and mature animals. In addition, both clozapine and olanzapine selectively reduced 5-HT_2A labeling in hippocampal CA₁ and CA₃ 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.