Kappa opioid regulation of anxiety-like behavior during acute ethanol withdrawal
- 作者：Glenn R. Valdez ; valdezg@gvsu.edu ; Erin Harshberger
- 关键词：DYN ; dynorphin ; KOR ; kappa opioid receptor ; nor-BNI ; norbinaltorphimine ; U50 ; 488 ; (trans)-3 ; 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclo-hexyl] benzeneacetamide ; CRF ; corticotropin-releasing factor ; NPY ; neuropeptide Y
- 刊名：Pharmacology Biochemistry and Behavior
- 出版年：2012
- 期刊代码：219_00913057
- 类别：med
- 出版时间：July, 2012
- 卷：102
- 期：1
- 页码：44-47
- 文件大小：591 K
摘要
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.