Up-regulation of D₃ dopamine receptor mRNA by neuroleptics

The effects of 14 days neuroleptic treatment on the expression of the D₃ dopamine receptor gene was investigated in rats using a sensitive polymerase chain reaction assay. In olfactory tubercle, D₃ mRNA levels increased following haloperidol (40%), pimozide (56%), and sulpiride (63%) administration, and in nucleus accumbens, levels increased after haloperidol (50%) and sulpiride (50%). D₃ expression in the motor striatum did not change with any antagonist tested. Clozapine did not affect D₃ expression in any brain region. These data suggest that dopamine antagonists can regulate the expression of the D₃ receptor in a brain region selective manner. The findings also suggest that the motor complications of chronic antipsychotic therapy are not due to D₃ receptor up-regulation in the striatum.