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, 5-HT, and 5-HT 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 and 5-HT receptors were found mostly across hippocampal and cortical brain regions following early aripiprazole and olanzapine treatment, while early risperidone treatment changed 5-HT receptor levels in the NAc and PFC. Lesser effects were uncovered in the female cohort with aripiprazole, olanzapine and risperidone to alter 5-HT and 5-HT 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 and 5-HT receptors in the adult brain.