Differential modulation of mu-opioid receptor-mediated antitussive activity by delta-opioid receptor agonists in mice.

We examined the effect of [D-Ala2]deltorphin II, a selective delta 2-opioid receptor agonist, on the antitussive effect of [D-Ala2, MePhe4,Gly-ol5]enkephalin (DAMGO), a selective mu-opioid receptor agonist. [D-Ala2]deltorphin (3 nmol i.c.v.) had no significant effect on the number of coughs. However, upon i.c.v. pretreatment with [D-Ala2]deltorphin II (3 nmol) the antitussive activity of DAMGO (0.03 nmol) was significantly enhanced. The enhancement of the antitussive activity of DAMGO caused by [D-Ala2]deltorphin II was prevented by a benzofuran derivative of naltrindole (0.1 mg/kg s.c.), a selective delta 2-opioid receptor antagonist. These results suggest that delta 2-opioid receptors may play a synergistic role in antitussive processes that are mediated by mu-opioid receptors.