title: nor-BNI Antagonism of Kappa Opioid Agonist-Induced Reinstatement of Ethanol-Seeking Behavior.
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.
authors.affiliation: Department of Psychology, Grand Valley State University, Allendale, MI, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Harshberger
authors.affiliation: Department of Psychology, Grand Valley State University, Allendale, MI, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Gilson
authors.affiliation: Department of Psychology, Grand Valley State University, Allendale, MI, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Gillett
authors.affiliation: Department of Psychology, Grand Valley State University, Allendale, MI, USA.
authors.forename: Jasmine H
authors.initials: JH
authors.lastname: Stone
authors.affiliation: Department of Psychology, Grand Valley State University, Allendale, MI, USA.
authors.forename: Laila
authors.initials: L
authors.lastname: El Amrani
authors.affiliation: Department of Psychology, Grand Valley State University, Allendale, MI, USA.
authors.forename: Glenn R
authors.identifier: 0000-0001-8337-1760
authors.initials: GR
authors.lastname: Valdez