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.