EXPRESSION OF MESSENGER-RNAS ENCODING DOPAMINE-RECEPTORS IN STRIATAL REGIONS IS DIFFERENTIALLY REGULATED BY MIDBRAIN AND HIPPOCAMPAL-NEURONS

The grutamate analogue kainic acid was injected into the hippocampus of intact or 6-hydroxydopamine deafferented rats to investigate the influence of hippocampal neurons on the expression of dopamine D-1 and D-2 receptor mRNAs in subregions of the striatal complex and possible modulation by dopaminergic neurons. Quantitative in situ hybridization using S-35-labeled oligonucleotide probes specific for dopamine D-1 and D-2 receptor mRNAs, respectively, were used. It was found that an injection of kainic acid into the hippacampal formation had alone no significant effect on dopamine D-1 or D-2 receptor mRNA levels in any of the analyzed striatal subregions in animals analyzed 4 h after the injections. Kainic acid stimulation in the hippocampus ipsilateral to the dopamine lesion produced an increase in D-1 receptor mRNA levels in the ipsilateral medial caudate-putamen, and a bilateral increase in core and shell of nucleus accumbens (ventral striatal limbic regions). A unilateral 6-hydroxydopamine lesion alone caused an increase in D-2 receptor mRNA in the lateral caudate-putamen (dorsal striatal motor region) ipsilateral to the lesion and an increase in D-1 receptor mRNA in the accumbens care ipsilateral to the lesion. However, in dopamine-lesioned animals, dopamine D-1 receptor mRNA levels were increased bilaterally in nucleus accumbens core and shell and in the ipsilateral medial caudate-putamen following kainic acid stimulation in the hippocampus ipsilateral to the dopamine lesion. These results indicate a differential regulation of the expression of dopamine D-1 and D-2 receptor mRNAs by midbrain and hippocampal neurons. Dopamine D-1 receptor mRNA levels are affected in ventral striatal limbic regions and regulated by a mechanism probably involving both glutamate and dopamine transmission. It appears that hippocampal and dopamine neurons interact in regulating dopamine D, receptor mRNA levels in the ventral striatum. In contrast, dopamine D-2 receptor mRNA levels are mainly affected in dorsal striatal motor regions, and only by dopamine deafferentation.