ROLE OF DOPAMINE IN THE PLASTICITY OF GLUTAMIC-ACID DECARBOXYLASE MESSENGER-RNA IN THE RAT FRONTAL-CORTEX AND THE NUCLEUS-ACCUMBENS

The modulatory role of dopamine (DA) on the expression of mRNA encodin g the large isoform of glutamic acid decarboxylase (GAD67), the biosyn thesis enzyme of gamma aminobutyric acid (GABA), was examined in GABA neurons of two structures innervated by DA neurons originating from th e ventral tegmental area (VTA): the medial frontal cortex (MFC) and th e nucleus accumbens (NAcc). A bilateral electrolytic lesion of VTA was performed in rats to produce a DA denervation of both the MFC and NAc c. The efficacy of VTA lesions was verified by measurement of locomoto r activity and by immunohistochemical detection of tyrosine hydroxylas e in the mesencephalon. GAD67 mRNA was detected by in situ hybridizati on histochemistry using a S-35-labelled cDNA probe. Densitometric anal ysis of GAD67 mRNA hybridization signals revealed in VTA-lesioned rats a significant decrease (-24%) in GAD67 mRNA levels in the prelimbic a rea of the MFC and no significant effect in the anterior cingulate are a or the frontoparietal cortex. Single cell analyses by computer-assis ted grain counting showed that the decrease in GAD67 mRNA levels in pr elimbic MFC was due to a change in GAD67 mRNA expression in a subpopul ation of GABA interneurons located in the deep cortical layers (V-VI). By contrast, in the NAcc of VTA-lesioned rats, GAD67 mRNA levels were significantly increased in the anterior part and in the core but were unchanged in the shell part. These results suggest that in two target structures of VTA DA neurons, GAD67 mRNA expression is, in normal con ditions, under a tonic stimulatory and a tonic inhibitory DA control i n the MFC and the NAcc respectively. A schematic diagram is proposed f or functional interactions between these structures.