The effect of selective opioid antagonists on butorphanol-induced feeding.
Butorphanol tartrate (BT) potently stimulates food intake in satiated rats. The opioid receptor profile of BT is complex and is dependent upon the assay and animal species studied. In the present study we utilized three selective opioid antagonists; namely beta-funaltrexamine (beta-FNA), naltrindole (NTI) and norbinaltorphimine (nor-BNI), to probe the opioid receptor profile of BT as an orexigenic agent. Intracerebroventricular administration of nor-BNI (kappa) antagonized the feeding effects of BT (8 mg/kg, s.c.) at doses of 1, 10 and 100 nmol at the 1-2 h time point and decreased feeding at all time points for the 10 nmol dose. After 1 h, the 100 nmol dose of nor-BNI decreased BT-induced feeding by about 72%. In contrast, intraventricular injection of only the highest dose of the selective mu opioid antagonist, beta-FNA (50 nmol), decreased BT-induced feeding. Intraventricular administration of the delta opioid agonist, NTI, failed to alter BT-induced feeding at doses as high as 50 nmol. These data suggest that BT is dependent upon the kappa and perhaps the mu opioid receptors to increase food intake in satiated rats.
Levine
A S
AS
Research and Medicine Service, Veterans Administration Medical Center, Minneapolis, MN 55417.
Grace
M
M
Portoghese
P S
PS
Billington
C J
CJ
D000818:Animals; D002077:Butorphanol / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000187:drug effects
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D009271:Naltrexone; C024524:beta-funaltrexamine; C055382:naltrindole; D002077:Butorphanol