Increased sensitivity of Zucker obese rats to naloxone is present at weaning.

Increased pituitary and plasma concentrations of opioid peptides in genetically obese rodents may be a cause or consequence of obesity. It has been shown that food intake is decreased more in adult genetically obese rats and mice than lean rats and mice by administration of naloxone, an opiate antagonist. Evidence for an opiate-mediated component in the development of rather than the consequence of obesity would be provided if young, not yet obese, genetically obese rats were more sensitive than lean rats to naloxone. In the present experiment two groups of male and female obese and lean Zucker rats, fasted for 2 hr before the onset of the dark portion of the 12-hr light-dark cycle, were administered 0.125 to 0.5 mg/kg naloxone or 0.5 to 2.0 mg/kg naloxone subcutaneously and 30- and 60-min food intakes were measured. In the group administered the lower doses of naloxone, obese rats of the three ages tested responded more than the lean rats after 30 min (70 vs. 79% of control, p less than 0.02). However, increased sensitivity occurred during the 0-60 min period in rats 4-5 weeks old and 0-30 min period in rats 8-9 and 12-13 weeks old. In the second group tested with the higher doses, the obese responded less than the lean rats (73 vs. 66% of control, p less than 0.05) and there was no difference in response after 0-60 min (66 vs. 61% of control, NS). Thus, increased sensitivity to threshold doses of naloxone occurs before the development of substantial obesity and therefore opiate peptides may play a causal role in obesity.