Activation of adenosine A1 receptors reduces anxiety-like behavior during acute ethanol withdrawal (hangover) in mice
Activation of adenosine A1 receptors reduces anxiety-like behavior during acute ethanol withdrawal (hangover) in mice
复制标题
DOI：
10.1038/sj.npp.1301001
复制
发表时间：
2006-10-01
影响因子：
7.6
通讯作者：
Takahashi, Reinaldo N.
中科院分区：
文献类型：
--
作者：
Prediger, Rui D. S.;da Silva, George E.;Takahashi, Reinaldo N.
在戒除慢性和急性酒精暴露的过程中，人类和啮齿动物都观察到焦虑的迹象增加，这是酒精复发的一个重要激励因素。一些报告表明，脑腺苷受体参与了酒精产生的不同行为，如运动不协调和催眠效应。此外，我们最近还证明了腺苷A(1)受体调节乙醇诱导的抗焦虑作用。在本研究中，我们评估了腺苷A(1)和A(2)A受体激动剂在减少小鼠急性酒精戒断(宿醉)时焦虑样行为的潜力。实验动物一次性腹腔注射生理盐水或乙醇(4g/kg)，间隔0.5~24小时后在高架迷宫中进行测试，结果表明，在酒精注射后12~18小时，宿醉引起的焦虑最为明显，表现为迷宫张开臂的探索明显减少。在这个时间间隔，乙醇被完全清除。在戒断高峰开始(18h)时，急性给予非抗焦虑剂量的腺苷和选择性腺苷A(1)受体激动剂2-氯-N6-环戊基腺苷(CCPA)，但不给予腺苷A(2A)受体激动剂N6-[2-(3，5-dimethoxyphenyl)-2-(2-methylphenyl)乙基]腺苷(DPMA)，可降低这种焦虑性反应。此外，选择性腺苷A(1)受体拮抗剂8-环戊基-1，3-二丙基黄嘌呤(DPCPX)可逆转CCPA对酒精宿醉焦虑样行为的影响。这些结果加强了腺苷受体参与焦虑样反应的概念，并表明腺苷A(1)受体激动剂有可能减少酒精戒断时的焦虑效应。
Elevated signs of anxiety are observed in both humans and rodents during withdrawal from chronic as well as acute ethanol exposure, and it represents an important motivational factor for ethanol relapse. Several reports have suggested the involvement of brain adenosine receptors in different actions produced by ethanol such as motor incoordination and hypnotic effects. In addition, we have recently demonstrated that adenosine A(1) receptors modulate the anxiolytic-like effect induced by ethanol in mice. In the present study, we evaluated the potential of adenosine A(1) and A(2)A receptor agonists in reducing the anxiety-like behavior during acute ethanol withdrawal (hangover) in mice. Animals received a single intraperitoneal administration of saline or ethanol (4 g/kg) and were tested in the elevated plus maze after an interval of 0.5-24 h. The results indicated that hangover-induced anxiety was most pronounced between 12 and 18 h after ethanol administration, as indicated by a significant reduction in the exploration of the open arms of the maze. At this time interval, ethanol was completely cleared. The acute administration of 'nonanxiolytic' doses of adenosine and the selective adenosine A(1) receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), but not the adenosine A(2A) receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl) ethyl] adenosine (DPMA), at the onset of peak withdrawal (18 h), reduced this anxiogenic-like response. In addition, the effect of CCPA on the anxiety-like behavior of ethanol hangover was reversed by pretreatment with the selective adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). These results reinforce the notion of the involvement of adenosine receptors in the anxiety-like responses and indicate the potential of adenosine A(1) receptor agonists to reduce the anxiogenic effects during ethanol withdrawal.