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 o f intact or 6-hydroxydopamine deafferented rats to investigate the inf luence of hippocampal neurons on the expression of dopamine D-1 and D- 2 receptor mRNAs in subregions of the striatal complex and possible mo dulation by dopaminergic neurons. Quantitative in situ hybridization u sing S-35-labeled oligonucleotide probes specific for dopamine D-1 and D-2 receptor mRNAs, respectively, were used. It was found that an inj ection of kainic acid into the hippacampal formation had alone no sign ificant effect on dopamine D-1 or D-2 receptor mRNA levels in any of t he analyzed striatal subregions in animals analyzed 4 h after the inje ctions. Kainic acid stimulation in the hippocampus ipsilateral to the dopamine lesion produced an increase in D-1 receptor mRNA levels in th e ipsilateral medial caudate-putamen, and a bilateral increase in core and shell of nucleus accumbens (ventral striatal limbic regions). A u nilateral 6-hydroxydopamine lesion alone caused an increase in D-2 rec eptor mRNA in the lateral caudate-putamen (dorsal striatal motor regio n) ipsilateral to the lesion and an increase in D-1 receptor mRNA in t he accumbens care ipsilateral to the lesion. However, in dopamine-lesi oned animals, dopamine D-1 receptor mRNA levels were increased bilater ally 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 different ial regulation of the expression of dopamine D-1 and D-2 receptor mRNA s by midbrain and hippocampal neurons. Dopamine D-1 receptor mRNA leve ls 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 regulati ng dopamine D, receptor mRNA levels in the ventral striatum. In contra st, dopamine D-2 receptor mRNA levels are mainly affected in dorsal st riatal motor regions, and only by dopamine deafferentation.