Targeting dynorphin/kappa opioid receptor systems to treat alcohol abuse and dependence

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• 作者：Brendan M. Walker^a ; ^{b_walker@wsu.edu} ; Glenn R. Valdez^b ; Jay P. McLaughlin^c ; Georgy Bakalkin^d
• 关键词：Alcohol ; Anxiety ; Central nucleus of the amygdala ; Cognitive dysfunction ; Decision making ; Dependence ; Depression ; Dynorphin ; Extended amygdala ; Impulsivity ; Kappa opioid receptor ; Negative affect ; Negative reinforcement ; Nor-binaltorphimine (nor-BNI) ; Nu
• 刊名：Alcohol
• 出版年：2012
• 期刊代码：1_07418329
• 类别：neu
• 出版时间：June, 2012
• 卷：46
• 期：4
• 页码：359-370
• 文件大小：386 K

摘要

This review represents the focus of a symposium that was presented at the 鈥淎lcoholism and Stress: A聽Framework for Future Treatment Strategies鈥?conference in Volterra, Italy on May 3-6, 2011 and organized/chaired by Dr. Brendan M. Walker. The primary goal of the symposium was to evaluate and disseminate contemporary findings regarding the emerging role of kappa-opioid receptors (KORs) and their endogenous ligands dynorphins (DYNs) in the regulation of escalated alcohol consumption, negative affect and cognitive dysfunction associated with alcohol dependence, as well as DYN/KOR mediation of the effects of chronic stress on alcohol reward and seeking behaviors. Dr. Glenn Valdez described a role for KORs in the anxiogenic effects of alcohol withdrawal. Dr. Jay McLaughlin focused on the role of KORs in repeated stress-induced potentiation of alcohol reward and increased alcohol consumption. Dr. Brendan Walker presented data characterizing the effects of KOR antagonism within the extended amygdala on withdrawal-induced escalation of alcohol self-administration in dependent animals. Dr. Georgy Bakalkin concluded with data indicative of altered DYNs and KORs in the prefrontal cortex of alcohol dependent humans that could underlie diminished cognitive performance. Collectively, the data presented within this symposium identified the multifaceted contribution of KORs to the characteristics of acute and chronic alcohol-induced behavioral dysregulation and provided a foundation for the development of pharmacotherapeutic strategies to treat certain aspects of alcohol use disorders.