Early antipsychotic exposure affects serotonin and dopamine receptor binding density differently in selected brain loci of male and female juvenile rats

• Olanzapine decreased 5-HT2A, 5-HT2C bindings in all frontal brain regions of both male and female juvenile rats.
• Risperidone decreased 5-HT2A, 5-HT2C bindings in the prefrontal cortex.
• Aripiprazole reduced the 5-HT2A bindings in the male PFC, but had no effects on 5-HT2C bindings.
• Early antipsychotic treatment had less effects on dopamine D1/D2 receptor bindings.
• Early antipsychotic treatment caused some gender-dependent changes.

BackgroundAntipsychotic drugs (APDs) were developed to treat schizophrenia in adults; however they have been increasingly prescribed (mostly “off-label”) for children and adolescents. This study aimed to investigate the effects of aripiprazole, olanzapine and risperidone on the binding of serotonin and dopamine receptors in juvenile rat brain regions that are involved in antipsychotic efficacy.MethodsMale and female rats were treated orally with aripiprazole (1 mg/kg), olanzapine (1 mg/kg), risperidone (0.3 mg/kg) or vehicle 3 times/day starting from postnatal day 23 (±1 day) for 20 days. Quantitative autoradiography was performed to examine the receptor binding densities.ResultsOlanzapine significantly decreased 5-HT2A (5-HT2AR) and 5-HT2C receptor (5-HT2CR) binding in the prefrontal cortex (PFC), cingulate cortex (Cg) and nucleus accumbens (NAc) of both male and female rats. In the caudate putamen (CPu), olanzapine attenuated 5-HT2AR binding in both genders, and reduced 5-HT2CR binding in male rats. Olanzapine increased D2 receptor (D2R) binding in the NAcS of male rats, but decreased it in females. Olanzapine increased D1 receptor (D1R) binding in the Cg, while aripiprazole decreased D1R binding in the PFC of males. Aripiprazole significantly reduced 5-HT2AR binding in the male PFC. Risperidone decreased 5-HT2AR binding in the PFC of female rats, while attenuating D1R binding in the PFC and Cg of males. However, APDs have no effects on the binding of serotonin and dopamine transporters.ConclusionThis study revealed that aripiprazole, olanzapine and risperidone affected 5-HT2AR, 5-HT2CR, 5-HTT, D1R and D2R bindings differently in the brains of juvenile male and female rats.

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