Decreased opioid-induced antinociception but unaltered G-protein activation in the genetic-diabetic NOD mouse

Previous evaluation of antinociceptive action in experimental diabetes has been conducted almost exclusively in chemically induced diabetes mellitus. The purpose of the present study was to evaluate antinociceptive response a nd G-protein activation by mu-opioid receptor and delta-opioid receptor ago nists in the genetic non-obese diabetic (NOD) mouse, a model of type I insu lin-dependent diabetes mellitus (IDDM). Tail-flick latency before and after hyperglycemia was unaltered. Hyperglycemic NOD mice were hyporesponsive to intracerebroventricular (i.c.v.) injections of [D-Ala(2)]deltorphin II but not to [D-Ala(2), N-MePhe(4), Gly-ol(5)]enkephalin (DAMGO); however, C-pro tein activation in pons/medulla assessed by [S-35]GTP gamma S binding was n ot diminished. This suggests that a G-protein defect in signaling cannot ac count for the hyporesponsiveness of antinociception in this genetic model o f IDDM. (C) 2000 Elsevier Science B.V. All rights reserved.