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首页> 外文期刊>Alcohol >Protracted withdrawal from ethanol and enhanced responsiveness stress: Regulation via the dynorphin/kappa opioid receptor system
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Protracted withdrawal from ethanol and enhanced responsiveness stress: Regulation via the dynorphin/kappa opioid receptor system

机译：长时间退出乙醇并增强反应压力：通过强啡肽/κ阿片受体系统进行调节

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Although recent work suggests that the dynorphin/kappa opioid receptor (DYN/KOR) system may be a key mediator in the stress-related effects of alcohol, the regulation of long-term changes associated with protracted withdrawal from ethanol via the DYN/KOR system has yet to be explored. The objective of the present study was to determine the role of the DYN/KOR system in the regulation of anxiety-related behaviors during an extended period of abstinence from ethanol in animals with a history of ethanol dependence. Male Wistar rats (n=94) were fed an ethanol or control liquid diet for 25-30 days. Six weeks after its removal, rats were exposed to 20min of immobilization, and the ability of the KOR antagonist nor-binaltorphimine (nor-BNI) (0-20mg/kg, intraperitoneal [i.p.]) to attenuate the enhanced responsiveness to stress observed in rats chronically exposed to ethanol was investigated using the elevated plus maze. In addition, the ability of U50,488 (0-10mg/kg, i.p.) to prime anxiety-like behavior during protracted withdrawal was also examined. Rats with a history of ethanol dependence showed a significant decrease in open-arm exploration after exposure to restraint, indicating an anxiety-like state, compared to similarly treated controls, an effect that was blocked by nor-BNI. nor-BNI also selectively decreased center time and open-arm approaches in ethanol-exposed rats. The highest dose of U50,488 decreased open-arm exploration and the total number of arm entries in ethanol-exposed and control rats. Although lower doses of U50,488 did not affect open-arm exploration in either group, the 0.1mg/kg dose selectively decreased motor activity in the ethanol-exposed rats when compared to similarly pretreated controls. These findings further support the hypothesis that behaviors associated with withdrawal from ethanol are in part regulated by the DYN/KOR system, and suggest that these effects may be long lasting in nature.
机译：尽管最近的工作表明强啡肽/κ阿片受体系统（DYN / KOR）可能是酒精与压力相关的作用的关键介体，但与通过DYN / KOR系统长期退出乙醇有关的长期变化的调控尚未探索。本研究的目的是确定DYN / KOR系统在有乙醇依赖史的动物长期戒酒期间在调节与焦虑相关的行为中的作用。给雄性Wistar大鼠（n = 94）喂食乙醇或对照流质饮食25-30天。移除大鼠六周后，将其暴露于固定状态20分钟，观察到KOR拮抗剂去甲双萘酚胺（nor-BNI）（0-20mg / kg，腹膜内[ip]）减弱了对应激反应的增强。使用高架迷宫研究了长期暴露于乙醇的大鼠。此外，还检查了U50,488（0-10mg / kg，i.p.）在长期停药期间引发焦虑样行为的能力。具有乙醇依赖病史的大鼠与受到类似治疗的对照组相比，暴露于束缚后的张开双臂探索显着减少，表明处于焦虑样状态，这种作用被nor-BNI阻断。 nor-BNI还可以选择性地减少乙醇暴露大鼠的中心时间和开臂方法。 U50,488的最高剂量减少了暴露于乙醇的大鼠和对照组大鼠的张开双臂探索和手臂进入总数。尽管在任何一组中较低剂量的U50,488都不会影响张开双臂的探查，但与类似预处理的对照组相比，0.1mg / kg的剂量选择性降低了暴露于乙醇的大鼠的运动活动。这些发现进一步支持了以下假设：与退出乙醇相关的行为部分受到DYN / KOR系统的调节，并表明这些影响在本质上可能是持久的。

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