纳洛酮拮抗κ 型阿片受体减少依赖诱导的大鼠过量饮酒。
Systemic κ-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats.
机构信息
The Scripps Research Institute, La Jolla, CA, USA.
出版信息
Addict Biol. 2011 Jan;16(1):116-9. doi: 10.1111/j.1369-1600.2010.00226.x.
Abstract
Altered dynorphin opioid peptide systems contribute to increased ethanol self-administration during withdrawal following chronic alcohol exposure. We previously identified that the κ-opioid receptor antagonist nor-binaltorphimine (nor-BNI) selectively reduced ethanol self-administration in dependent animals. The purpose of this study was twofold: (1) determine whether peripherally administered nor-BNI could reduce dependence-induced ethanol self-administration and (2) confirm the selective κ-opioid effects of nor-BNI by administering it 24 hours prior to ethanol self-administration sessions occurring during acute withdrawal. Nor-BNI decreased ethanol self-administration in ethanol-dependent animals, with no effect in nondependent animals. Thus, the κ-opioid/dynorphin system is a viable pharmacotherapeutic target for the treatment of alcoholism.
摘要
改变的内啡肽阿片肽系统有助于慢性酒精暴露后戒断期间增加乙醇的自我给药。我们之前发现 κ 阿片受体拮抗剂诺丁啡（nor-BNI）选择性地减少了依赖动物的乙醇自我给药。本研究的目的有两个：（1）确定外周给予 nor-BNI 是否可以减少依赖诱导的乙醇自我给药；（2）通过在急性戒断期间发生的乙醇自我给药之前 24 小时给予 nor-BNI，来确认 nor-BNI 的选择性 κ 阿片受体效应。nor-BNI 减少了乙醇依赖动物的乙醇自我给药，但对非依赖动物没有影响。因此，κ 阿片肽/内啡肽系统是治疗酒精中毒的可行药物治疗靶点。
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