THE ABILITIES OF SPECIFIC KAPPA-OPIOID AGONISTS, U-50,488H AND U-62,066E, TO CAUSE ANTITUSSIVE TOLERANCE WERE LOWER THAN THAT OF MORPHINE

We examined whether the chronic administration of selective kappa-opioid agonists could produce antitussive tolerance, in a comparison with the mu-opioid morphine. A certain degree of tolerance to the antitussive effects of morphine appeared in rats treated chronically with this drug. However, chronic administration of U-50,488H and U-62,066E, highly selective agonists for the kappa-opioid receptor, does not result in the development of tolerance to their respective antitussive effects. These results suggest that the ability of kappa-opioid agonists to cause tolerance to their respective antitussive effects was lower than that of a mu-opioid agonist.