Modulation of μ-mediated antitussive activity In rats by a δ agonist

Abstract

Effects of selective μ, and δ receptor agonists on capsaicin-induced cough reflex in rats were studied. Intracisternal injection (i.cist.) of a selective μ receptor agonist [D-Ala²Mephe⁴Gly-ol⁵]enkephalin (DAMGO) produced dose-relaieu depression of coughs over the 0.003-0.03 nmol dose range. The antitussive potency of DAMGO was 100-fold more potent than morphine. The antitussive effects of DAMGO and morphine were significantly reduced by naloxone (1 nmol i.cist.). The selective δ receptor agonist, [D-Pen²D-Pen⁵]enkephalin (DPDPE), at a dose of 10 nmol (i.cist.), had no significant effect on the number of coughs. When co-administered i.cist., DPDPE (10 nmol) consistently and significantly decreased the antitussive potencies of DAMGO and morphine. The decrease in the antitussive effects of DAMGO and morphine caused by DPDPE were prevented by selective δ receptor antagonist, naltrindole (3 nmol). These results suggest that the antitussive effects of opioids are mediated predominantly by μ receptors, and δ receptors may play an inhibitory role in antitussive processes that are mediated by the μ receptors.