The effects of antipsychotics on the density of cannabinoid receptors in selected brain regions of male and female adolescent juvenile rats

Antipsychotic drugs have been increasingly prescribed to children and adolescents for treating various mental disorders, such as childhood-onset schizophrenia. The abnormality of endocannabinoid system is involved in the pathophysiology of these disorders in juveniles. This study investigated the effect of antipsychotics on the cannabinoid (CB) receptors in the brain of both male and female juvenile rats. The postnatal rats (PD23±1) were administered aripiprazole (1 mg/kg), olanzapine (1 mg/kg), risperidone (0.3 mg/kg) or vehicle (control) for 3 weeks. Quantitative autoradiography was used to investigate the binding densities of [ 3 H]CP-55940 (an agonist for CB1R and CB2R) and [ 3 H]SR141716A (a selective CB1R antagonist) in the rat brains. Risperidone significantly upregulated the [ 3 H]CP55940 and [ 3 H]SR141716A bindings in the prefrontal cortex (PFC), nucleus accumbens core (NAcC), nucleus accumbens shell (NAcS), cingulate cortex (Cg), and the caudate putamen (CPu) in male rats. Moreover, aripiprazole significantly elevated the [ 3 H]SR141716A binding in the Cg and NAcS of female rats. Furthermore, there is an overall higher [ 3 H]SR141716A binding level in the brain of female rats than male rats. Therefore, treatment with aripiprazole, olanzapine and risperidone could induce differential and gender specific effects on the binding density of cannabinoid receptors in the selected brain regions of childhood/adolescent rats.