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 administrat ion of short-acting general opioid antagonists produces transient effe cts. The present study evaluated whether chronic central administratio n of selective long-acting antagonists of mu (beta-funaltrexamine, BFN A, 20 mu g), mu(1) (naloxonazine, 50 mu g), delta(1) ([D-Ala(2),Leu(5) ,Cys(6)]-enkephalin, DALCE, 40 mu g), delta(2) (naltrindole isothiocya nate, NTII, 20 mu g) or kappa (nor-binaltorphamine, NBNI, 20 mu g) opi oid receptor subtypes altered weight and intake of rats exposed to a p alatable diet of pellets, fat, milk and water, relative to pellet-fed and diet-fed controls. Diet-fed rats receiving chronic vehicle injecti ons 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 chron ic NBNI. All antagonists chronically reduced fat intake, but did not s ystematically alter total intake, pellet intake or milk intake relativ e to the pattern of weight loss. These data indicate that central mu, mu(1), delta(1), delta(2), and, to a lesser degree, kappa receptors me diate long-term opioid modulation of weight even in animals maintained on diets that ultimately result in dietary obesity.