Evaluation of chronic opioid receptor antagonist effects upon weight and intake measures in lean and obese Zucker rats.

Body weight and food intake are significantly reduced in rats during development of dietary obesity following chronic central administration of mu (beta-funaltrexamine, BFNA), mu1 (naloxonazine), kappa1 (nor-binaltorphamine, NBNI), delta1 ([D-Ala2,Leu5,Cys6]-enkephalin, DALCE) and delta2 (naltrindole isothiocyanate, NTII) opioid receptor subtype antagonists. In contrast, rats made obese by maintainance on a 'cafeteria' diet failed to display weight loss following chronic mu1 receptor antagonism. To test the hypothesis that chronic administration of opioid antagonists are less effective in controlling intake and weight in obese animals, the present study assessed whether chronic, central administration of either BFNA (20 micrograms), naloxonazine (50 micrograms), NBNI (20 micrograms), DALCE (40 micrograms) or NTII (20 micrograms) altered weight and intake in lean and obese Zucker rats over seven days. Body weight was reduced following chronic mu (lean: 42 g; obese: 49 g), mu1 (lean: 71 g; obese: 38 g), kappa1 (lean: 30 g; obese 14 g), delta1 (lean: 43 g; obese: 22 g) or delta2 (lean: 37.5 g; obese: 36 g) antagonism. Overall food intake was reduced following chronic mu (lean: 8.8 g; obese: 16.1 g), mu1 (lean: 12.6 g; obese: 17.0 g), kappa1 (lean: 6.5 g; obese 7.0 g), delta1 (lean: 9.7 g; obese: 11.1 g) or delta2 (lean: 9.4 g; obese: 14.3 g) antagonism. Therefore, both lean and obese Zucker rats display weight loss and reduced intake following chronic central administration of opioid receptor subtype antagonists.