Kappa-opioid receptor blockade with nor-binaltorphimine modulates cocaine self-administration in drug-naive rats.
The modulation of the reinforcing effects of cocaine by the kappa-opioid receptor antagonist, nor-binaltorphimine was studied by using the initiation of intravenous self-administration in drug-naive Wistar rats. Treatment with nor-binaltorphimine (3.0 mg/kg s.c.) 48 h before the start of the first of five daily self-administration sessions significantly decreased the intake of cocaine when offered in a threshold unit dose (30 micrograms per infusion), but had no effect on cocaine intake when it was offered in a higher unit dose (60 micrograms per infusion). It is concluded that blockade of the kappa-opioid receptor by nor-binaltorphimine may produce a rightward shift of the unit dose-response relationship of cocaine reward, thus decreasing the sensitivity to cocaine reward. These data suggest an involvement of endogenous kappa-opioid systems in the mechanisms underlying the initiation of cocaine self-administration behaviour.
Kuzmin
A V
AV
Laboratory of Pharmacology of Narcotics, Pavlov Medical University, St.-Petersburg, Russian Federation.
Gerrits
M A
MA
Van Ree
J M
JM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D012646:Self Administration; D013997:Time Factors
D009294:Narcotics; D018733:Nicotinic Antagonists; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D003042:Cocaine