Opiates and medial hypothalamic knife cuts cause hyperphagia through different mechanisms.
Several experiments were performed to determine whether the hyperphagia caused by medial hypothalamic knife cuts and that induced by opiate agonists are mediated by a common mechanism. In the first set of experiments, male Sprague-Dawley rats were given bilateral parasagittal medial hypothalamic knife cuts or a sham procedure and fed a high-fat Crisco-chow diet. Knife-cut and sham-operated rats were approximately equally sensitive to the suppressive effects of naloxone on food intake. The kappa opiate receptor agonist ketocyclazocine generally increased daytime food intake in sham-operated rats; in contrast, the normal hyperphagia of knife-cut rats was in most cases either unchanged or decreased by ketocyclazocine. In a second set of experiments, neither diet composition nor hypothalamic knife cuts significantly affected the feeding responses to naloxone or the stimulatory effects of the kappa agonist butorphanol tartrate. It was hypothesized that the differential effects of ketocyclazocine in knife-cut and sham-operated rats are a consequence of the sedative effects of the drug combined with the elevated baseline of the knife-cut subjects. This hypothesis was supported by a third experiment, in which ketocyclazocine also reduced nocturnal intake in unoperated rats and butorphanol increased intake. That feeding responses to naloxone and butorphanol were essentially unchanged by hypothalamic knife cuts suggests that the opioid feeding system is independent of the longitudinal feeding inhibitory pathway believed to be involved in knife-cut-induced hyperphagia.
D000818:Animals; D001931:Brain Mapping; D002077:Butorphanol / Q000494:pharmacology; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects*; D016314:Ethylketocyclazocine / Q000031:analogs & derivatives*; D007033:Hypothalamus, Middle / Q000502:physiology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D011957:Receptors, Opioid; D009270:Naloxone; D016314:Ethylketocyclazocine; C012395:ketazocine; D003496:Cyclazocine; D002077:Butorphanol