THE EFFECT OF CHRONIC TREATMENT WITH NALTRINDOLE, A SELECTIVE DELTA-OPIOID ANTAGONIST, ON MU-OPIOID RECEPTOR-MEDIATED ANTINOCICEPTION IN DIABETIC MICE

The effects of chronic treatment with naltrindole (NTI), a selective d elta-opioid receptor antagonist, on the antinociceptive effects of mu- opioid agonists, such as morphine and [D-Ala(2), N-MePhe(4), Gly-ol(5) ]enkephalin (DAMGO) were examined in diabetic mice. Antinociception in duced by morphine (10 mu g, ICV) and DAMGO (0.5 mu g, ICV) was signifi cantly lower in diabetic mice than in non-diabetic mice. The low sensi tivities to the antinociceptive potencies of ICV morphine (10 mu g) an d DAMGO (0.5 mu g) in diabetic mice were reversed compared with those in saline-treated non-diabetic mice when diabetic mice had been pretre ated with NTI (2 mg/kg per day, SC) for 14 days. Naive mice which had been injected with spleen mononuclear cells from saline-treated diabet ic mice were less sensitive to DAMGO-induced antinociception. However, adoptive transfer of spleen mononuclear cells from NTI-treated diabet ic mice to naive mice had no effect on the recipients' antinociceptive sensitivity to DAMGO. These results suggest that the effect of NTI on the sensitivity to mu-opioid agonists in diabetic mice may be due to the immunosuppressive effects of NTI.