title: κ opioid regulation of anxiety-like behavior during acute ethanol withdrawal.
abstract: Withdrawal 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.
authors.affiliation: Department of Psychology, Grand Valley State University, Allendale, MI, United States. valdezg@gvsu.edu
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Valdez
authors.forename: Erin
authors.initials: E
authors.lastname: Harshberger
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology / Q000627:therapeutic use; D000437:Alcoholism / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology
chemical_list: D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D000431:Ethanol; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer