• Glenn R Valdez and Erin Harshberger.
• Department of Psychology, Grand Valley State University, Allendale, MI, United States. valdezg@gvsu.edu
• Pharmacol. Biochem. Behav. 2012 Jul 1; 102 (1): 44-7.

AbstractWithdrawal is one of the defining characteristics of alcohol dependence, and is often characterized by impaired physiological function and enhanced negative affect. Recent evidence suggests that the dynorphin (DYN)/kappa opioid receptor (KOR) system may be a key mediator in the negative affect often associated with drugs of abuse. The objective of the present experiments was to determine the role of the DYN/KOR system in the regulation of anxiety-related behavior during acute withdrawal from ethanol. Rats were fed an ethanol liquid diet and following removal, the ability of the KOR antagonist nor-BNI to attenuate the increased anxiogenic-like response characteristic of ethanol withdrawal was investigated using the elevated plus maze. A comparison study was also conducted examining anxiety-related behavior following direct activation of KORs via injections of the KOR agonist U50,488. Rats experiencing ethanol withdrawal showed a significant decrease in open arm exploration compared to controls, an effect that was blocked by nor-BNI. Similar decreases in open arm exploration were observed following injections with the KOR agonist, U50,488, an effect also reversed by pretreatment with nor-BNI. These results suggest that similar mechanisms are involved in the regulation of ethanol withdrawal- and KOR agonist-induced changes in behavior. Given the potential role of enhanced negative affect in persistent ethanol drinking, understanding the role of the DYN/KOR system in regulating anxiety associated with withdrawal may be critical in understanding the factors associated with the nature of alcohol dependence.Copyright © 2012 Elsevier Inc. All rights reserved.

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