Selective alterations in macronutrient intake of food-deprived or glucoprivic rats by centrally-administered opioid receptor subtype antagonists in rats

Two hypotheses have attempted to account for the abilities of opioid agonists and antagonists to respectively stimulate and inhibit food intake in rats. The first suggests that the opioid system selectively modulates fat intake, while the second suggests that the opioid system selectively alters intake of that macronutrient which the animal prefers. The present study evaluated these two hypotheses by examining total intake and individual macronutrient intake in either food-deprived (24 h) rats or rats made glucoprivic with 2-deoxy-d-glucose (2DG, 200 mg/kg, i.p.) following either vehicle treatment systemic administration of naltrexone or intracerebroventricular administration of either naltrexone, the mu opioid antagonist, beta-funaltrexamine (B-FNA), the mu₁ opioid antagonist, naloxonazine, the kappa opioid antagonist, nor-binaltorphamine (Nor-BNI), the delta opioid antagonist, naltrindole or the delta₁ opioid antagonist, DALCE. Systemic administration of naltrexone (0.5-5 mg/kg) significantly reduced carbohydrate, fat and total intake in deprived rats, and carbohydrate, fat, protein and total intake in glucoprivic rats. Central administration of naltrexone (5-50 μg) significantly reduced fat and total intake in both deprived and glucoprivic rats. B-FNA (5-20 ug) significantly reduced carbohydrate, fat and total intake in both deprived and glucoprivic rats. Naloxonazine (10-100 μg) significantly reduced carbohydrate, fat and total intake in deprived rats, but failed to alter 2DG intake. Nor-BNI (5-20 ug) significantly reduced fat and total intake in glucoprivic rats, but failed to alter deprivation intake. Neither naltrindole (20 μg) nor DALCE (40 μg) altered intake in deprived or glucoprivic rats. Carbohydrate or fat preference in deprived rats significantly increased the amount of explained variance in the inhibitory actions of central naltrexone, B-FNA and naloxonazine upon deprivation-induced intake. Carbohydrate or fat preference in glucoprivic rats significantly increased the amount of explained variance in the inhibitory actions of systemic and central naltrexone, B-FNA, naloxonazine and Nor-BNI upon 2-DG hyperphagia. These data are discussed in terms of the contentions that opioids either selectively alter fat intake per se or selectively alter the preferred macronutrient.