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.
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Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD 20892, USA.
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006120:Grooming; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D015260:Neprilysin / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*
D004151:Dipeptides; D011480:Protease Inhibitors; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C062344:SCH 32615; D015260:Neprilysin