EFFECT OF CHRONIC TREATMENT WITH TYPICAL AND ATYPICAL NEUROLEPTICS ONTHE EXPRESSION OF DOPAMINE D-2 AND D-3 RECEPTORS IN RAT-BRAIN

The effect of chronic treatment (21 days) with typical and atypical ne uroleptics on the expression of striatal and limbic D-2 and D-3 dopami ne receptors was investigated in rat brain by in situ hybridization an d receptor autoradiography. Haloperidol and sulpiride increased D-2 re ceptor expression in striatal and limbic areas. In contrast, clozapine had no effect on D-2 receptor expression. Haloperidol decreased D-3 r eceptor expression in limbic areas, with the exception of the islands of Calleja where an increase occurred. Sulpiride and clozapine increas ed D-3 receptor expression in limbic and striatal regions but decrease d D-3 receptor expression in the islands of Calleja. This study demons trates that chronic treatment with typical and atypical neuroleptics p roduces different regionally specific changes in limbic and striatal D -2 and D-3 receptor expression, The alterations in dopamine receptor e xpression 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 Comparison of mRNA levels in animals which were not withdrawn from drug treatmen t with those that were withdrawn, demonstrated that some changes in re ceptor expression occurred during drug treatment, whilst others only m anifested when drug treatment had ceased. The different regulation of dopamine D-2 and D-3 receptor expression by typical and atypical neuro leptics may have relevance to the ability of these drugs to cause extr apyramidal side-effects.