MEDIATION OF INSULIN HYPERPHAGIA BY SPECIFIC CENTRAL OPIATE RECEPTOR ANTAGONISTS

The hyperphagic properties of insulin (10 U/kg, s.c.) were transiently (2 h) and dose-dependently inhibited (30%) by central pretreatment with naltrexone (20-50-mu-g, i.c.v.). The irreversible mu opioid antagonist, beta-funaltrexamine (B-FNA, 20-mu-g, i.c.v.) significantly inhibited insulin hyperphagia by 28-54% over the 6-h time course. In contrast, insulin hyperphagia was only transiently (2 h) inhibited (27-30%) by either the irreversible mu-1 antagonist, naloxonazine (50-mu-g, i.c.v.) or the selective kappa antagonist, nor-binaltorphamine (NorBNI, 20-mu-g, i.c.v.). The delta-antagonistic actions of [D-Ala2,Leu5,Cys6]-enkephalin (DALCE, 40-mu-g, i.c.v.) failed to affect insulin hyperphagia. These data suggest that the mu-2 opioid receptor subtype modulates insulin hyperphagia.