Nor-BNI Antagonism of Kappa Opioid Agonist-Induced Reinstatement of Ethanol-Seeking Behavior. (6th November 2016)

• Record Type: Journal Article
• Authors: Harshberger, Erin; Gilson, Emily A.; Gillett, Kelli; Stone, Jasmine H.; El Amrani, Laila; Valdez, Glenn R.
• Other Names: Vendruscolo Leandro F. Academic Editor.
• Is Part Of: Journal of addiction. Volume 2016(2016)
• Publication Date: 2016-11-06
• Subjects: Substance abuse -- Periodicals; Compulsive behavior -- Periodicals; 362.2905
• DOI: 10.1155/2016/1084235
• Languages: English
• ISSNs: 2090-7834

Abstract

Abstract : 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.