Systemic kappa-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats

Altered dynorphin opioid peptide systems contribute to increased ethanol self-administration during withdrawal following chronic alcohol exposure. We previously identified that the kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) selectively reduced ethanol self-administration in dependent animals. The purpose of this study was twofold: (1) determine whether peripherally administered nor-BNI could reduce dependence-induced ethanol self-administration and (2) confirm the selective kappa-opioid effects of nor-BNI by administering it 24 hours prior to ethanol self-administration sessions occurring during acute withdrawal. Nor-BNI decreased ethanol self-administration in ethanol-dependent animals, with no effect in nondependent animals. Thus, the kappa-opioid/dynorphin system is a viable pharmacotherapeutic target for the treatment of alcoholism.