Reductions in body weight following chronic central opioid receptor subtype antagonists during development of dietary obesity in rats.

Acute administration of long-acting general opioid antagonists reduces body weight and food intake in rats. In contrast, chronic administration of short-acting general opioid antagonists produces transient effects. The present study evaluated whether chronic central administration of selective long-acting antagonists of mu (beta-funaltrexamine, BFNA, 20 micrograms), mu1 (naloxonazine, 50 micrograms), delta1 ([D-Ala2,Leu5,Cys6]-enkephalin, DALCE, 40 micrograms), delta2 (naltrindole isothiocyanate, NTII, 20 micrograms) or kappa (nor-binaltorphamine, NBNI, 20 micrograms) opioid receptor subtypes altered weight and intake of rats exposed to a palatable diet of pellets, fat, milk and water, relative to pellet-fed and diet-fed controls. Diet-fed rats receiving chronic vehicle injections significantly increased weight (7-10%) and intake over the 11-day time course. Weight was significantly reduced over the time course in rats administered either BFNA (9%), naloxonazine (12%), DALCE (7%) or NTII (6%). Initial weight reductions failed to persist following chronic NBNI. All antagonists chronically reduced fat intake, but did not systematically alter total intake, pellet intake or milk intake relative to the pattern of weight loss. These data indicate that central mu, mu1, delta1, delta2, and, to a lesser degree, kappa receptors mediate long-term opioid modulation of weight even in animals maintained on diets that ultimately result in dietary obesity.