Origin of the stimulation of food intake by oral administration of enkephalinase inhibitors in sheep.

The influence of two enkephalinase inhibitors (thiorphan and acetorphan) orally, parenterally and centrally administered on food intake was tested in hay-fed ewes. When orally administered at a dose of 1 mg/kg, acetorphan, but not thiorphan, produced a biphasic increase in food intake corresponding to a 17.0% increase of daily food intake. Similarly thiorphan (0.1 mg X kg-1) IV administered increased by 19.3% the daily food intake; in contrast acetorphan IV administered produced a early (0-2 h) decrease followed by a late increase in hay consumption without significant (P greater than 0.05) change in the daily food intake. When ICV administered (10 micrograms X kg-1) thiorphan but not acetorphan at the same dose depressed the early (0-2 h) and daily food intake by 43.2% and 25.4% respectively. Pretreatment with naltrexone (0.1 mg X kg-1 IV) blocked the increased food intake induced by oral acetorphan or IV acetorphan and thiorphan but did not affect the anorectic effects of ICV thiorphan. We conclude that enkephalinase inhibitors like thiorphan and acetorphan increase daily food intake in sheep probably by increasing enkephalin levels in peripheral tissues.