Proenkephalin mRNA levels in rat striatum are increased and decreased, respectively, by selective D2 and D1 dopamine receptor antagonists.

Rats were treated for 3 days with the selective D1 dopamine receptor antagonist SCH23390 (250 micrograms/kg i.p., 3 x daily), the selective D2 dopamine receptor antagonist YM-09151-M (500 micrograms/kg i.p., 2 x daily), or saline. The levels of striatal proenkephalin mRNA were then assayed by in-situ hybridisation histochemistry, using a synthetic oligonucleotide probe. Following YM-09151-M treatment, proenkephalin mRNA levels were dramatically raised in the striatum, compared to animals receiving vehicle injections. In contrast, rats treated with SCH23390 showed decreased striatal levels of proenkephalin mRNA. The results demonstrate that selective D2 receptor blockade leads to enhanced proenkephalin gene expression in rat striatum, while selective D1 receptor antagonism has the opposite effect.