Mediation of insulin hyperphagia by specific central opiate receptor antagonists

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