Long-term effects of olanzapine, risperidone, and quetiapine on dopamine receptor types in regions of rat brain: Implications for antipsychotic drug treatment

Changes in members of the dopamine (DA) D-1-like (D-1, D-5) and D-2-like (D -2, D-3, D-4) receptor families in rat forebrain regions were compared by q uantitative in vitro receptor autoradiography after prolonged treatment (28 days) with the atypical antipsychotics olanzapine, risperidone, and quetia pine. Olanzapine and risperidone, but not quetiapine, significantly increas ed D-2 binding in medial prefrontal cortex (MPC; 67% and 34%), caudate-puta men (CPu; average 42%, 25%), nucleus accumbens (NAc; 37%, 28%), and hippoca mpus (HIP; 53%, 30%). Olanzapine and risperidone, but not quetiapine, produ ced even greater up-regulation of D-4 receptors in CPu (61%, 37%), NAc (65% , 32%), and HIP (61%, 37%). D-1-like and D-3 receptors in all regions were unaltered by any treatment, suggesting their minimal role in mediating acti ons of these antipsychotics. The findings support the hypothesis that antip sychotic effects of olanzapine and risperidone are partly mediated by D-2 r eceptors in MPC, NAc, or HIP, and perhaps D-4 receptors in CPu, NAc, or HIP , but not in cerebral cortex. Selective up-regulation of D-2 receptors by o lanzapine and risperidone in CPu may reflect their ability to induce some e xtrapyramidal effects. Inability of quetiapine to alter DA receptors sugges ts that nondopaminergic mechanisms contribute to its antipsychotic effects.