Activation of Brain NOP Receptors Attenuates Acute and Protracted Alcohol Withdrawal Symptoms in the Rat
Activation of Brain NOP Receptors Attenuates Acute and Protracted Alcohol Withdrawal Symptoms in the Rat
复制标题
DOI：
10.1111/j.1530-0277.2010.01392.x
复制
发表时间：
2011-04-01
影响因子：
3.2
通讯作者：
Ciccocioppo, Roberto
中科院分区：
文献类型：
--
作者：
Economidou, Daina;Cippitelli, Andrea;Ciccocioppo, Roberto
背景：酒精戒断是指在长期或长期摄入酒精后突然停止使用酒精而可能出现的一系列症状。这些症状使戒酒变得困难，并增加了戒酒康复者复发的风险。在以前的研究中，我们证明了诺西汀/孤儿FQ(N/OFQ)治疗显著减少了大鼠的酒精摄入量，并减轻了由环境条件因素或应激诱导的酒精寻求行为。在本研究中，我们评估了脑内NOP受体的激活是否也可以减轻大鼠的酒精戒断症状。方法：给动物灌胃6天的慢性酒精中毒，在停止酒精暴露后8，10和12小时，脑室内注射N/OFQ(0.0，1.0和3.0mgg/只)。ICV治疗后对躯体戒断症状进行评分。在随后的实验中，为了评价N/OFQ对酒精戒断诱导的焦虑的影响，另一组大鼠被给予乙醇中毒，并在1周后在高架+迷宫(EPM)中测试焦虑行为。在最后一次实验中，另一组大鼠被测试急性酒精中毒引起的焦虑(宿醉焦虑)。为此，动物接受急性剂量(3.0g/kg)的20%酒精，12h后在icv N/OFQ(0.0，1.0和2.0mU/g/鼠)后检测EPM。结果：N/OFQ显著减少慢性和急性酒精中毒引起的躯体戒断体征的表达，并逆转焦虑样行为。结论：N/OFQ-NOP受体系统可能是改善酒精戒断症状新疗法的一个有希望的靶点。
Background:Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with Nociceptin/orphanin FQ (N/OFQ) significantly reduces alcohol consumption and attenuates alcohol-seeking behavior induced by environmental conditioning factors or by stress in rats. In this study, we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats.Methods:For this purpose, animals were subjected to a 6-day chronic alcohol intoxication (by intragastric administration), and at 8, 10, and 12 hours following cessation of alcohol exposure, they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0, and 3.0 mu g/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety, another group of rats was subjected to ethanol intoxication and after 1 week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment, an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12 hour later were tested in the EPM following ICV N/OFQ (0.0, 1.0, and 2.0 mu g/rat).Results:Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals.Conclusions:These findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms.