Repeated antipsychotic drug exposure in developing rats: dopamine receptor effects

Antipsychotic drugs are often prescribed to juvenile psychiatric patients, though their cerebral effects during development are incompletely described. Accordingly, we studied the effects of repeated treatment with dissimilar antipsychotic drugs on dopamine (DA) receptors in juvenile vs. adult rats. Tissue levels of DA receptor types (D1, D2, D3, and D4) in forebrain regions of juvenile rats were quantified after 3 weeks of daily treatment with representative first- (fluphenazine) and second-generation (clozapine and olanzapine) antipsychotics, and compared with similarly treated adult rats examined in previous studies. Fluphenazine, clozapine, and olanzapine all decreased D1 receptors in dorsolateral frontal and medial prefrontal cortex (MPC) of juvenile, but not adult rats. Conversely, all three test agents increased D2 labeling in MPC of adult, but not young animals. Fluphenazine and olanzapine, but not clozapine, also increased D2 receptor levels in hippocampus, and D4 levels in nucleus accumbens (NAc) and caudate-putamen (CPu) in both juvenile and adult brain. D3 receptors were not altered by any treatment in any brain region at either age. Only some DA receptor adaptations to antipsychotic treatment are shared by developing and mature animals. Developmental differences in DA receptor responses may account for differences in clinical effects of antipsychotic drugs between young and adult psychiatric patients.