A comparison of the effects of the short-acting
opioid antagonist naloxone, with the irreversible and highly-specific mu-1 antagonist
naloxonazine, has categorized the mediation of
opioids in some forms of feeding into mu-1 and non-mu-1 components. The mu-1 sites have been implicated in free-feeding, deprivation-induced feeding and
morphine-induced
hyperphagia, based upon their sensitivity to both
naloxone and
naloxonazine. However, the ability of
naloxone, but not
naloxonazine to inhibit feeding, induced by either
2-deoxy-D-glucose glucoprivation,
ethylketocyclazocine,
dynorphin or (D-ala2., D-leu5.)-enkephalin implies the existence of non-mu-1
opioid receptor mechanisms in these responses. The present study compared the effects of the daily administration of
naloxone and
naloxonazine (10 mg/kg, i.v.) in rats in three different types of maturational or dietary situations. In adult rats,
naloxonazine and
naloxone significantly reduced
body weight (7% and 4%, respectively) and food intake (21% and 13%, respectively) over 14 days. These effects were more pronounced in adolescent rats where
naloxonazine and
naloxone significantly reduced the gain in
body-weight (53% and 33%, respectively) and food intake (24% and 15%, respectively) over 14 days. In the adolescent rats, the effects of
naloxonazine were significantly greater than those of
naloxone. In contrast, chronic treatment with neither
naloxone nor
naloxonazine altered
body weight or food intake of rats made obese by dietary manipulations and left on that diet during treatment with antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)