Reduction by central beta-funaltrexamine of food intake in rats under freely-feeding, deprivation and glucoprivic conditions.
The present study evaluated the central effects of beta-funaltrexamine (B-FNA), a non-equilibrium antagonist of mu-opioid receptors and a reversible agonist of kappa-opioid receptors upon food intake in rats under freely-feeding, deprivation and glucoprivic conditions. B-FNA elicited distinct short-term and long-term actions, consistent with binding studies demonstrating its reversible kappa agonist actions and its irreversible mu receptor blockade. Whereas B-FNA (1-20 micrograms, i.c.v.) significantly stimulated free feeding for up to 6 h, B-FNA (10-20 micrograms) significantly inhibited (35-41%) free feeding at 24, 48 and 72 h after injection, a pattern temporally similar to its biochemical opioid effects. Pretreatment (24 h) with B-FNA (10-20 micrograms) significantly inhibited (33-49%) the increased intake following 24 h of food deprivation. Pretreatment (24 h) with B-FNA (10-20 micrograms) also significantly inhibited (75-100%) the increased glucoprivic intake induced by 2-deoxy-D-glucose. The short-term stimulation of food intake by central B-FNA was antagonized by the selective kappa antagonist, nor-binaltorphamine, but was unaffected by pretreatment 24 h earlier with the mu antagonist, B-FNA. Significant reductions in striatal (89%) and hypothalamic (46%) mu-opioid binding occurred in rats pretreated (24 h) with B-FNA; the low levels of delta binding in these structures precluded interpretation of B-FNA effects. These data indicate the importance of the mu-opioid receptor in the modulation of different forms of feeding behavior, and underscores the ability of selective opioid antagonists to delineate precise functional roles for different opioid receptor subtypes.
Arjune
D
D
Department of Psychology, Queens College, CUNY, Flushing 11367.
Standifer
K M
KM
Pasternak
G W
GW
Bodnar
R J
RJ
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects*; D005508:Food Deprivation / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage*; D007031:Hypothalamus / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013997:Time Factors
D004040:Dietary Carbohydrates; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D009271:Naltrexone; C024524:beta-funaltrexamine; D005947:Glucose