Regulation of striatal enkephalin turnover in rats receiving antagonists of specific dopamine receptor subtypes.

The hypothesis that striatal dopamine regulates enkephalin (ENK) synthesis is supported by the increase of striatal proenkephalin mRNA and ENK after intranigral injection of 6-hydroxydopamine. In order to elucidate which dopamine receptor subtype is operative in the regulation of the dynamic state of ENK, the effect of drugs that block D-1 or D-2 receptor selectively was studied. Daily administration of 140 mumol/kg s.c. of the D-2 antagonist I-sulpiride twice daily for 2 weeks produces a 30% decrease in the content of striatal proenkephalin mRNA and ENK. In contrast, a 50% increase was observed after 2 weeks of treatment with the D-1 antagonist SCH 23390 at 74 nmol/kg s.c. three times a day. Hence, it can be inferred that the endogenous activation of D-1 tonically decreases striatal ENK synthesis. Removal of this neurally mediated regulation either by a specific pharmacologic blockage of D-1 or by lesioning with 6-hydroxydopamine increases the biosynthesis of ENK. The increase of ENK biosynthesis elicited by denervation with 6-hydroxydopamine cannot be due to the endogenous activation of D-2 receptors and must be due to the inactivation of the tonic inhibition exerted by D-1 receptors.