DOPAMINE D-3 RECEPTORS ARE NOT INVOLVED IN THE INDUCTION OF C-FOS MESSENGER-RNA BY NEUROLEPTIC DRUGS - COMPARISON OF THE DOPAMINE D-3 RECEPTOR ANTAGONIST GR103691 WITH TYPICAL AND ATYPICAL NEUROLEPTICS

The effect of acute and chronic administration of dopamine receptor an tagonists on the expression of mRNA encoding the cellular immediate-ea rly gene c-fos was investigated in rat brain by in situ hybridization using S-35-labelled oligonucleotide probes. The selective dopamine D-3 receptor antagonist GR103691 had no effect on the level of c-fos mRNA after acute or chronic treatment. Acute treatment with haloperidol in creased the level of c-fos mRNA in the caudate-putamen, nucleus accumb ens shell and core, olfactory tubercle and parietal cortex. After chro nic treatment with haloperidol increases in the level of c-fos mRNA in the caudate-putamen and nucleus accumbens core were no longer observe d. The increase in the level of c-fos mRNA in the nucleus accumbens sh ell was attenuated but still significantly elevated above the level me asured in vehicle-treated animals. In the olfactory tubercle, parietal cortex, frontal cortex and cingulate cortex the level of c-fos mRNA w as decreased after chronic haloperidol treatment. Acute sulpiride trea tment reduced the level of c-fos mRNA in the olfactory tubercle, parie tal cortex and cingulate cortex. After chronic treatment with sulpirid e the level of c-fos mRNA was reduced in the dorsal caudate-putamen on ly. Acute clozapine treatment increased the level of c-fos mRNA in the nucleus accumbens shell and islands of Calleja. After chronic treatme nt with clozapine the level of c-fos mRNA remained elevated in the isl ands of Calleja but not in the nucleus accumbens shell. These results indicate that acute and chronic blockade of dopamine D-3 receptors doe s not cause induction of c-fos transcription in limbic, striatal or co rtical regions of rat brain. This study also demonstrated that acute b lockade of dopamine receptors with haloperidol, sulpiride and clozapin e induced different regionally specific patterns of c-fos expression w hich were altered after chronic blockade.