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.