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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‐HT1A, and 5‐HT2A 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‐HT1A receptors in medial prefrontal cortex (MPC) and dorsolateral frontal cortex (DFC) of juvenile and adult rats. Clozapine and olanzapine also increased 5‐HT1A labeling in hippocampal CA1 and CA3 regions of juvenile but not adult animals. Repeated treatments with clozapine and olanzapine, but not fluphenazine, decreased 5‐HT2A receptors in MPC and DFC in developing and mature animals. In addition, both clozapine and olanzapine selectively reduced 5‐HT2A 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.