PT  - JOURNAL ARTICLE
AU  - Frank I. Tarazi
AU  - Kehong Zhang
AU  - Ross J. Baldessarini
TI  - Long-Term Effects of Olanzapine, Risperidone, and Quetiapine on Dopamine Receptor Types in Regions of Rat Brain: Implications for Antipsychotic Drug Treatment
DP  - 2001 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 711--717
VI  - 297
IP  - 2
4099  - http://jpet.aspetjournals.org/content/297/2/711.short
4100  - http://jpet.aspetjournals.org/content/297/2/711.full
SO  - J Pharmacol Exp Ther2001 May 01; 297
AB  - Changes in members of the dopamine (DA) D1-like (D1, D5) and D2-like (D2, D3, D4) receptor families in rat forebrain regions were compared by quantitative in vitro receptor autoradiography after prolonged treatment (28 days) with the atypical antipsychotics olanzapine, risperidone, and quetiapine. Olanzapine and risperidone, but not quetiapine, significantly increased D2binding in medial prefrontal cortex (MPC; 67% and 34%), caudate-putamen (CPu; average 42%, 25%), nucleus accumbens (NAc; 37%, 28%), and hippocampus (HIP; 53%, 30%). Olanzapine and risperidone, but not quetiapine, produced even greater up-regulation of D4 receptors in CPu (61%, 37%), NAc (65%, 32%), and HIP (61%, 37%). D1-like and D3 receptors in all regions were unaltered by any treatment, suggesting their minimal role in mediating actions of these antipsychotics. The findings support the hypothesis that antipsychotic effects of olanzapine and risperidone are partly mediated by D2 receptors in MPC, NAc, or HIP, and perhaps D4 receptors in CPu, NAc, or HIP, but not in cerebral cortex. Selective up-regulation of D2 receptors by olanzapine and risperidone in CPu may reflect their ability to induce some extrapyramidal effects. Inability of quetiapine to alter DA receptors suggests that nondopaminergic mechanisms contribute to its antipsychotic effects. The American Society for Pharmacology and Experimental Therapeutics