Early antipsychotic exposure affects NMDA and GABAA receptor binding in the brains of juvenile rats

Antipsychotics were developed to treat schizophrenia in adults; however they have been increasingly prescribed in children and adolescents. The NMDA and GABA_A receptors are involved in neurodevelopment and the pathophysiology of various mental disorders in children and adolescents. Male and female juvenile rats were treated orally with risperidone (0.3 mg/kg, 3 times/day), aripiprazole (1 mg/kg), olanzapine (1 mg/kg) or vehicle (control), starting from postnatal day (PD) 23 (±1 day) for 3 weeks (corresponding to the childhood-adolescent period in humans). Quantitative autoradiography was used to detect the binding density of [³H]MK-801 (an NMDA receptor antagonist) and [³H]muscimol (a selective GABA_A receptor agonist). Aripiprazole elevated the [³H]MK801 binding levels in the NAcC of male rats, and the NAcS and CPu of female rats. Risperidone increased [³H]MK801 levels in the CPu of female rats, and the NAcS of male rats. Aripiprazole upregulated [³H]muscimol binding levels in the CPu and NAcC of male rats, while it elevated the [³H]muscimol levels in the PFC of female rats, compared to controls. These results suggest that early treatment with these antipsychotics modulates NMDA and GABA_A neurotransmission in juveniles, which may play a role in their clinical efficacy in the control of mental disorders in children and adolescents.