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Journal of Addiction
Volume 2016 (2016), Article ID 1084235, 8 pages
Research Article

nor-BNI Antagonism of Kappa Opioid Agonist-Induced Reinstatement of Ethanol-Seeking Behavior

Department of Psychology, Grand Valley State University, Allendale, MI, USA

Received 12 August 2016; Accepted 10 October 2016

Academic Editor: Leandro F. Vendruscolo

Copyright © 2016 Erin Harshberger et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Recent work suggests that the dynorphin (DYN)/kappa opioid receptor (KOR) system may be a key mediator in the behavioral effects of alcohol. The objective of the present study was to examine the ability of the KOR antagonist norbinaltorphimine (nor-BNI) to attenuate relapse to ethanol seeking due to priming injections of the KOR agonist U50,488 at time points consistent with KOR selectivity. Male Wistar rats were trained to self-administer a 10% ethanol solution, and then responding was extinguished. Following extinction, rats were injected with U50,488 (0.1–10 mg/kg, i.p.) or saline and were tested for the reinstatement of ethanol seeking. Next, the ability of the nonselective opioid receptor antagonist naltrexone (0 or 3.0 mg/kg, s.c.) and nor-BNI (0 or 20.0 mg/kg, i.p.) to block U50,488-induced reinstatement was examined. Priming injections U50,488 reinstated responding on the previously ethanol-associated lever. Pretreatment with naltrexone reduced the reinstatement of ethanol-seeking behavior. nor-BNI also attenuated KOR agonist-induced reinstatement, but to a lesser extent than naltrexone, when injected 24 hours prior to injections of U50,488, a time point that is consistent with KOR selectivity. While these results suggest that activation of KORs is a key mechanism in the regulation of ethanol-seeking behavior, U50,488-induced reinstatement may not be fully selective for KORs.