Early antipsychotic treatment in juvenile rats elicits long-term alterations to the adult serotonin receptors

BACKGROUND: Antipsychotic drug (APD) prescription/use in children has increased significantly worldwide, despite limited insight into potential long-term effects of treatment on adult brain functioning. While initial long-term studies have uncovered alterations to behaviors following early APD treatment, further investigations into potential changes to receptor density levels of related neurotransmitter (NT) systems are required. METHODS: The current investigation utilized an animal model for early APD treatment with aripiprazole, olanzapine, and risperidone in male and female juvenile rats to investigate potential long-term changes to the adult serotonin (5-HT) NT system. Levels of 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptors were measured in the prefrontal cortex (PFC), caudate putamen (CPu), nucleus accumbens (NAc), and hippocampus via Western Blot and receptor autoradiography. RESULTS: In the male cohort, long-term changes to 5-HT(2A) and 5-HT(2C) receptors were found mostly across hippocampal and cortical brain regions following early aripiprazole and olanzapine treatment, while early risperidone treatment changed 5-HT(1A) receptor levels in the NAc and PFC. Lesser effects were uncovered in the female cohort with aripiprazole, olanzapine and risperidone to alter 5-HT(1A) and 5-HT(2A) receptors in NAc and hippocampal brain regions, respectively. CONCLUSION: The results of this study suggest that early treatment of various APDs in juvenile rats may cause gender and brain regional specific changes in 5-HT(2A) and 5-HT(2C) receptors in the adult brain.