Engagement of the brain orexin system in activity-based anorexia behaviour in mice

While excessive physical activity is common amongst anorexia nervosa (AN) patients, contributing to their low body weight, little is known about the underlying biology and effective treatments targeting the hyperactivity are lacking. Given the role of orexin in arousal, physical activity and energy expenditure, we sought to investigate i) the extent to which orexin neurons are activated during severe anorectic state in the activity-based anorexia (ABA) mouse model, and ii) if the dual orexin receptor antagonist suvorexant can reduce physical activity during ABA. The Fos-TRAP2 technique enable us to visually capture active neurons (Fos expressing) during severe anorectic state in the ABA mouse model, and by immunohistochemistry, determine the extent to which these active neurons are orexin positive. In addition, suvorexant was administered peripherally to ABA mice and running activity was monitored. We found that a large population of orexin neurons in the hypothalamus are activated by ABA and that peripheral administration of suvorexant decreases food anticipatory activity in these mice. We conclude that orexin may be a suitable target to treat hyperactivity in AN and recommend further studies to examine the efficacy of suvorexant in aiding AN patients to control their drive for hyperactivity. (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Automated summary

This study aims to investigate the activation of orexin neurons during severe anorectic state and the potential of suvorexant, a dual orexin receptor antagonist, in reducing excessive physical activity. The findings indicate that a large population of orexin neurons are activated in the ABA mouse model and that peripheral administration of suvorexant decreases food anticipatory activity. Orexin may be a suitable target for treating hyperactivity in AN, and further research is recommended to examine the efficacy of suvorexant in aiding AN patients in controlling excessive activity.