Effects of SCH 32615, an enkephalinase inhibitor, on D-1 and D-2 dopamine receptor-mediated behaviors.

Striatal enkephalin-containing neurons receive dopaminergic inputs from the substantia nigra and project to the external segment of globus pallidus. These neurons express primarily dopamine (DA) D-2 receptors. Accordingly, stimulation of enkephalinergic transmission might be expected to influence mainly D-2 receptor agonist or antagonist effects on motor function. To test this hypothesis, the effects of SCH 32615, an enkephalinase inhibitor, on DA antagonist-induced catalepsy, DA D-1 agonist-induced non-stereotyped grooming, and DA D-2 agonist-induced stereotyped behavior were studied. The administration of SCH 32615 (3 mg/kg) decreased both D-1 and D-2 antagonist-induced catalepsy. In contrast, SCH 32615 (0.3 mg/kg) increased D-1 agonist-induced non-stereotyped grooming and D-2 agonist-induced stereotypies. These results suggest that a DA agonist-like, mostly D-2 activity may be involved in enkephalinergic-mediated functions.