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