Effect of chronic treatment with typical and atypical neuroleptics on the expression of dopamine D2 and D3 receptors in rat brain

Abstract

The effect of chronic treatment (21 days) with typical and atypical neuroleptics on the expression of striatal and limbic D₂ and D₃ dopamine receptors was investigated in rat brain by in situ hybridization and receptor autoradiography. Haloperidol and sulpiride increased D₂ receptor expression in striatal and limbic areas. In contrast, clozapine had no effect on D₂ receptor expression. Haloperidol decreased D₃ receptor expression in limbic areas, with the exception of the islands of Calleja where an increase occurred. Sulpiride and clozapine increased D₃ receptor expression in limbic and striatal regions but decreased D₃ receptor expression in the islands of Calleja. This study demonstrates that chronic treatment with typical and atypical neuroleptics produces different regionally specific changes in limbic and striatal D₂ and D₃ receptor expression. The alterations in dopamine receptor expression were different for each drug, but a distinction between the effects of atypical and typical neuroleptics could be made. Comparison of mRNA levels in animals which were not withdrawn from drug treatment with those that were withdrawn, demonstrated that some changes in receptor expression occurred during drug treatment, whilst others only manifested when drug treatment had ceased. The different regulation of dopamine D₂ and D₃ receptor expression by typical and atypical neuroleptics may have relevance to the ability of these drugs to cause extrapyramidal side-effects.