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

• Published in: Journal of pharmacological sciences Vol. 156; no. 2; pp. 86 - 101
• Main Authors: AlSharari, Shakir D., Alameen, Alaa A., Aldafiri, Fawzeyah S., Ali, Yousif S., Alshammari, Musaad A., Sari, Youssef, Damaj, M.I.
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 01.10.2024
• Subjects: alpha7 Nicotinic Acetylcholine Receptor - metabolism; Animals; Anxiety; Anxiety - etiology; Behavior, Animal - drug effects; Benzamides - administration & dosage; Benzamides - pharmacology; Bridged Bicyclo Compounds - pharmacology; Eating - drug effects; Eating disorders; Hyperalgesia - etiology; Hyperalgesia - metabolism; Male; Mice; Mice, Inbred C57BL; Obesity; Obesity - metabolism; Obesity - psychology; Pain; Weight Gain - drug effects; Withdrawal; α7 nicotinic receptors; α7 nicotinic receptors; Obesity; Anxiety; Pain; Withdrawal; Eating disorders
• ISSN: 1347-8613; 1347-8648; 1347-8648
• DOI: 10.1016/j.jphs.2024.07.006

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.