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

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 alpha 7-nicotinic acetylcholine receptors (alpha 7nAChR) 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 (alpha 7nAChR 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. alpha 7nAChR activation attenuated anxiolytic-like behavior and hyperalgesia in PF abstinent mice. These data suggest potential therapeutic effects of targeting alpha 7 nAChRs for obesity-withdrawal symptoms in obese subjects.