LACK OF INVOLVEMENT OF DELTA-1 OPIOID RECEPTORS IN THE DEVELOPMENT OFPHYSICAL-DEPENDENCE ON MORPHINE IN MICE

Previously, we have shown that the development of physical dependence on morphine in mice is inhibited substantially by treatment of mice wi th the highly selective, nonequilibrium delta-2 opioid receptor antago nist, naltrindole-5'-isothiocyanate. With the availability of the high ly selective, nonequilibrium delta-1 opioid receptor antagonist, [D-Al a(2),Leu(5),Cys(6)]enkephalin, it was possible, in the present report, to examine the possible involvement of delta-1 opioid receptors in th e development of opiate dependence. Mice were made physically dependen t on morphine by s.c. implantation of morphine pellets (75-mg free bas e) for 3 days. The degree of dependence was quantified by determining the ED(50) values of naloxone to precipitate withdrawal jumping and di arrhea. Neither sign of opiate withdrawal was affected by chronic trea tment of animals with [D-Ala(2),Leu(5),Cys(6)]enkephalin during the mo rphine implant period. The data suggest that delta-1, as opposed to de lta-2, opioid receptors are not involved in the development of physica l dependence on morphine. This fact takes on added significance becaus e the recently cloned delta opioid receptors appear to be the delta-2 subtype and the present data together with previous findings suggest t hat the cloned receptors may be proper models for the study of opiate dependence.