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-opio id receptor antagonist, nor-binaltorphimine was studied by using the i nitiation 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 signific antly decreased the intake of cocaine when offered in a threshold unit dose (30 mu g per infusion), but had no effect on cocaine intake when it was offered in a higher unit dose (60 mu g per infusion). It is co ncluded that blockade of the kappa-opioid receptor by nor-binaltorphim ine may produce a rightward shift of the unit dose-response relationsh ip of cocaine reward, thus decreasing the sensitivity to cocaine rewar d. These data suggest an involvement of endogenous kappa-opioid system s in the mechanisms underlying the initiation of cocaine self-administ ration behaviour. (C) 1998 Elsevier Science B.V. All rights reserved.