Long-Term Effects of Olanzapine,Risperidone,and Quetiapine on Dopamine Receptor Types in Regions of Rat Brain: Implications for Antipsychotic Drug Treatment

摘要

Changes in members of the dopamine (OA) 01-like (01' 05) and D2-like (02' 03' 04) receptor families in rat forebrain regions were compared by quantitative in vitro receptor autoradiogra- phy after prolonged treatment (28 days) with the atypical anti- psychotics olanzapine, risperidone, and quetiapine. Olanzapine and risperidone, but not quetiapine, significantly increased O2 binding in medial prefrontal cortex (MPC; 67% and 34%), cau- date-putamen (CPu; average 42%, 25%), nucleus accumbens (NAc; 37%, 28%), and hippocampus (HIP; 53%, 30%). Olan- zapine and risperidone, but not quetiapine, produced even greater up-regulation of 04 receptors in CPu (61 %, 37%), NAc (65%, 32%), and HIP (61 %, 37%). 01-like and 03 receptors in all regions were unaltered by any treatment, suggesting their minimal role in mediating actions of these anti psychotics. The findings support the hypothesis that antipsychotic effects of olanzapine and risperidone are partly mediated by O2 receptors in MPC, NAc, or HIP, and perhaps 04 receptors in CPu, NAc, or HIP, but not in cerebral cortex. Selective up-regulation of O2 receptors by olanzapine and risperidone in CPu may reflect their ability to induce some extrapyramidal effects. Inability of quetiapine to alter OA receptors suggests that nondopaminer- gic mechanisms contribute to its antiDsvchotic effects.