Blockade of ethanol reward by the kappa opioid receptor agonist U50,488H

被引:52
|
作者
Logrip, Marian L. [1 ,2 ]
Janak, Patricia H. [1 ,2 ,3 ]
Ron, Dorit [1 ,2 ,3 ]
机构
[1] Ernest Gallo Res Ctr, Emeryville, CA 94608 USA
[2] Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
关键词
Dynorphin; Kappa opioid receptor; Reward; Ethanol; CPP; CONDITIONED PLACE PREFERENCE; STRIATAL DOPAMINE LEVELS; MESSENGER-RNA CONTENT; BRAIN-REGIONS; COCAINE; ACTIVATION; DYNORPHIN; STRESS; SENSITIZATION; INCREASES;
D O I
10.1016/j.alcohol.2009.05.001
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
Alcoholism is a pervasive social problem, and thus understanding factors that regulate alcohol (ethanol) reward is important for designing effective therapies. One putative regulatory system includes the kappa opioid receptor (KOR) and its endogenous ligand, dynorphin. Previously, we demonstrated that acute ethanol increased preprodynorphin expression via brain-derived neurotrophic factor (BDNF) in striatal neurons, and that blockade of the KOR attenuated decreases in ethanol intake observed following increased expression of BDNF. As high doses of KOR agonists can generate an aversive state, we hypothesized that endogenous dynorphin may regulate ethanol intake by interfering with the rewarding properties of ethanol. We found that low, nonaversive doses of the KOR agonist U50,488H blocked the rewarding properties of ethanol during conditioning, thus impairing the acquisition of conditioned place preference. Importantly, we demonstrate that U50,488H also inhibited the conditioned increase in locomotor activation normally observed in the ethanol-paired chamber on test day. Taken together, these data indicate that the KOR/dynorphin system may acutely regulate ethanol intake via inhibition of the rewarding properties of ethanol. (C) 2009 Elsevier Inc. All rights reserved.
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页码:359 / 365
页数:7
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