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α7 型烟碱型乙酰胆碱受体激动剂可减轻美味致肥胖饮食戒断引起的痛觉过敏和焦虑。

Activation of α7 nicotinic receptors attenuated hyperalgesia and anxiety induced by palatable obesogenic diet withdrawal.

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

出版信息

J Pharmacol Sci. 2024 Oct;156(2):86-101. doi: 10.1016/j.jphs.2024.07.006. Epub 2024 Jul 22.

Abstract

UNLABELLED

Consumption of palatable food (PF) can alleviate anxiety, and pain in humans. Contrary, spontaneous withdrawal of long-term PF intake produces anxiogenic-like behavior and abnormal pain sensation, causing challenges to weight-loss diet and anti-obesity agents. Thus, we examined α7-nicotinic acetylcholine receptors (α7nAChR) involvement since it plays essential role in nociception and psychological behaviors.

METHODS

Adult male C57BL/6 mice were placed on a Standard Chow (SC) alone or with PF on intermittent or continuous regimen for 6 weeks. Then, mice were replaced with normal SC (spontaneous withdrawal). Body weight, food intake, and calories intake with and without the obesogenic diet were measured throughout the study. During PF withdrawal, anxiety-like behaviors and pain sensitivity were measured with PNU-282987 (α7nAChR agonist) administration.

RESULTS

Six weeks of SC + PF-intermittent and continuous paradigms produced a significant weight gain. PF withdrawal displayed hyperalgesia and anxiety-like behaviors. During withdrawal, PNU-282987 significantly attenuated hyperalgesia and anxiety-like behaviors.

CONCLUSION

The present study shows that a PF can increase food intake and body weight. Also, enhanced pain sensitivity and anxiety-like behavior were observed during PF withdrawal. α7nAChR activation attenuated anxiolytic-like behavior and hyperalgesia in PF abstinent mice. These data suggest potential therapeutic effects of targeting α7 nAChRs for obesity-withdrawal symptoms in obese subjects.

摘要

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人类食用美味食物(PF)可以缓解焦虑和疼痛。相反,长期自发停止摄入 PF 会产生焦虑样行为和异常疼痛感觉,给减肥饮食和抗肥胖药物带来挑战。因此,我们研究了α7-烟碱型乙酰胆碱受体(α7nAChR)的参与,因为它在痛觉和心理行为中起着重要作用。

方法

成年雄性 C57BL/6 小鼠单独或在间歇性或连续性方案中接受标准食物(SC)和 PF 喂养 6 周。然后,用正常 SC(自发退出)替换小鼠。在整个研究过程中测量体重、食物摄入量和卡路里摄入量,有无致肥胖饮食。在 PF 退出期间,用 PNU-282987(α7nAChR 激动剂)给药测量焦虑样行为和疼痛敏感性。

结果

SC+PF 间歇性和连续性方案 6 周导致体重显著增加。PF 退出显示出痛觉过敏和焦虑样行为。在退出期间,PNU-282987 显著减轻了痛觉过敏和焦虑样行为。

结论

本研究表明,PF 可以增加食物摄入和体重。此外,在 PF 退出期间观察到疼痛敏感性和焦虑样行为增强。α7nAChR 激活减轻了 PF 戒断小鼠的焦虑样行为和痛觉过敏。这些数据表明,针对α7 nAChR 可能为肥胖患者的戒断症状提供潜在的治疗效果。

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