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

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

Abstract

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.

Keywords: Anxiety; Eating disorders; Obesity; Pain; Withdrawal; α7 nicotinic receptors.

MeSH terms

  • Animals
  • Anxiety* / etiology
  • Behavior, Animal / drug effects
  • Benzamides* / administration & dosage
  • Benzamides* / pharmacology
  • Bridged Bicyclo Compounds* / pharmacology
  • Eating / drug effects
  • Hyperalgesia* / etiology
  • Hyperalgesia* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Obesity* / metabolism
  • Obesity* / psychology
  • Weight Gain / drug effects
  • alpha7 Nicotinic Acetylcholine Receptor* / metabolism

Substances

  • alpha7 Nicotinic Acetylcholine Receptor
  • Benzamides
  • Bridged Bicyclo Compounds
  • PNU-282987