TY - JOUR
T1 - Lack of involvement of delta-1 opioid receptors in the development of physical dependence on morphine in mice
AU - Miyamoto, Y.
AU - Bowen, W. D.
AU - Portoghese, P. S.
AU - Takemori, A. E.
PY - 1994/1/1
Y1 - 1994/1/1
N2 - Previously, we have shown that the development of physical dependence on morphine in mice is inhibited substantially by treatment of mice with the highly selective, nonequilibrium delta-2 opioid receptor antagonist, naltrindole-5'-isothiocyanate. With the availability of the highly selective, nonequilibrium delta-1 opioid receptor antagonist, [D- Ala2,Leu5,Cys6]enkephalin, it was possible, in the present report, to examine the possible involvement of delta-1 opioid receptors in the development of opiate dependence. Mice were made physically dependent on morphine by s.c. implantation of morphine pellets (75-mg free base) for 3 days. The degree of dependence was quantified by determining the ED50 values of naloxone to precipitate withdrawal jumping and diarrhea. Neither sign of opiate withdrawal was affected by chronic treatment of animals with [D-Ala2,Leu5,Cys6]enkephalin during the morphine implant period. The data suggest that delta-1, as opposed to delta-2, opioid receptors are not involved in the development of physical dependence on morphine. This fact takes on added significance because the recently cloned delta opioid receptors appear to be the delta-2 subtype and the present data together with previous findings suggest that the cloned receptors may be proper models for the study of opiate dependence.
AB - Previously, we have shown that the development of physical dependence on morphine in mice is inhibited substantially by treatment of mice with the highly selective, nonequilibrium delta-2 opioid receptor antagonist, naltrindole-5'-isothiocyanate. With the availability of the highly selective, nonequilibrium delta-1 opioid receptor antagonist, [D- Ala2,Leu5,Cys6]enkephalin, it was possible, in the present report, to examine the possible involvement of delta-1 opioid receptors in the development of opiate dependence. Mice were made physically dependent on morphine by s.c. implantation of morphine pellets (75-mg free base) for 3 days. The degree of dependence was quantified by determining the ED50 values of naloxone to precipitate withdrawal jumping and diarrhea. Neither sign of opiate withdrawal was affected by chronic treatment of animals with [D-Ala2,Leu5,Cys6]enkephalin during the morphine implant period. The data suggest that delta-1, as opposed to delta-2, opioid receptors are not involved in the development of physical dependence on morphine. This fact takes on added significance because the recently cloned delta opioid receptors appear to be the delta-2 subtype and the present data together with previous findings suggest that the cloned receptors may be proper models for the study of opiate dependence.
UR - http://www.scopus.com/inward/record.url?scp=0028339388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028339388&partnerID=8YFLogxK
M3 - Article
C2 - 8035333
AN - SCOPUS:0028339388
SN - 0022-3565
VL - 270
SP - 37
EP - 39
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -