STREPTOZOTOCIN-INDUCED DIABETES SELECTIVELY ENHANCES ANTINOCICEPTION MEDIATED BY DELTA-(1)-OPIOID BUT NOT DELTA-(2)-OPIOID RECEPTORS

We assessed the effect of diabetes on antinociception produced by intracerebroventricular injection of delta-opioid receptor agonists [D-Pen(2,5)]enkephalin (DPDPE) and [D-Ala(2)]deltorphin II. The antinociceptive effect of DPDPE (10 nmol), administered i.c.v., was significantly greater in diabetic mice than in non-diabetic mice. The antinociceptive effect of i.c.v. DPDPE was significantly reduced in both diabetic and non-diabetic mice following pretreatment with 7-benzylidenenaltrexone (BNTX), a selective delta(1)-opioid receptor antagonist, but not with naltriben (NTB), a selective delta(2)-opioid receptor antagonist. There were no significant differences in the antinociceptive effect of [D-Ala(2)]deltorphin II (3 nmol, i.c.v.) in diabetic and non-diabetic mice. Furthermore, the antinociceptive effect of i.c.v. [D-Ala(2)]deltorphin II was significantly reduced in both diabetic and non-diabetic mice following pretreatment with NTB, but not with BNTX. In conclusion, mice with diabetes are selectively hyper-responsive to supraspinal delta(1)-opioid receptor-mediated antinociception, but are normally responsive to activation of delta(2)-opioid receptors.