A high-dose of fentanyl induced delayed anxiety-like behavior in rats. Prevention by a NMDA receptor antagonist and nitrous oxide (N2O)
A high-dose of fentanyl induced delayed anxiety-like behavior in rats. Prevention by a NMDA receptor antagonist and nitrous oxide (N2O)
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DOI：
10.1016/j.pbb.2012.07.002
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发表时间：
2012-10-01
影响因子：
3.6
通讯作者：
Simonnet, Guy
中科院分区：
文献类型：
--
作者：
Bessiere, Baptiste;Laboureyras, Emilie;Simonnet, Guy
术后的负面影响，如焦虑，需要更好地理解和治疗，以改善患者的恢复。本研究评价了单次暴露于高剂量阿片类药物（以15分钟间隔注射4 x 100 μ g/kg芬太尼，导致总剂量为400 μ g/kg）对大鼠焦虑样行为（ALB）的影响，该阿片类药物用于人类手术。首先，使用高架十字迷宫装置评估高剂量芬太尼后24小时的焦虑水平。其次，评估了BN 2572（一种N-甲基-D-天冬氨酸受体（NMDA-R）拮抗剂）和50%一氧化二氮（N2 O）（一种具有NMDA-R拮抗剂特性的气体）的预防效果。在芬太尼治疗的大鼠中观察到ALB显着增加。有趣的是，芬太尼诱导的ALB被BN 2572阻止，表明NMDA依赖性途径。芬太尼诱导的ALB也可以通过单次50%N2O暴露来预防。本研究提供的证据表明，阿片类药物使用的有害结果，称为“阿片类药物后综合征”，不仅包括如前所述的疼痛超敏反应，还包括焦虑等负面影响。由于N2 O可以预防阿片后综合征的发生，我们推测N2 O可能是一种良好的治疗药物，有助于术后康复。(c)2012 Elsevier Inc. All rights reserved.
Postoperative negative affects such as anxiety need to be better understood and treated to improve patient recovery. The present study evaluates the effect of a single exposure to a high-dose of opioid (4 x 100 mu g/kg fentanyl injections in 15 min intervals resulting in a total dose of 400 mu g/kg), as used for surgery in humans, on anxiety-like behavior (ALB) in rats. First, the level of anxiety was evaluated 24-h after a high-dose of fentanyl using an elevated plus-maze apparatus. Second, the preventive effect of BN2572, a N-methyl-D-aspartate receptor (NMDA-R) antagonist, and 50% nitrous oxide (N2O), a gas with NMDA-R antagonist properties, was assessed. A significant increase in ALB was observed in fentanyl-treated rats. Interestingly, fentanyl-induced ALB was prevented by BN2572, suggesting a NMDA-dependant pathway. Fentanyl-induced ALB was also prevented by a single 50% N2O exposure. The present study provides evidence that deleterious outcomes of opioid use, referred to as "post-opioid syndrome", include not only pain hypersensitivity as previously described, but also negative affects such as anxiety. Since N2O prevents elements of this post-opioid syndrome, we speculate that N2O could be a good therapeutic agent to facilitate postoperative rehabilitation. (c) 2012 Elsevier Inc. All rights reserved.