Investigating the Role of Orexin in Stress-Induced Binge Eating in Female Mice

Background Binge eating is a core feature of both bulimia nervosa and binge eating disorder, which impacts approximately 4-5% of adults, globally. Stress has been identified as a major antecedent to binge eating episodes, particularly in women. However, further research is needed to identify the neurobiological mechanisms driving female, stress-induced binge eating and thus develop effective pharmacological treatments. The orexin neuropeptide system is known to play a critical role in both stress and feeding-related behaviours, hence represents a promising candidate for further research. Aims & Objectives We aimed to investigate the role of orexin in female stress-induced binge eating using a mouse model. We hypothesised that orexin neurons would be recruited as a result of this behaviour, and that administration of an orexin-1 receptor antagonist (SB-334867) would reduce stress-induced binge eating. Method Our model comprised of repeated cycles of exposure to a mild stressor and intermittent access to palatable food to induce binge-like eating in female mice. Animals were administered either SB-334867 (15 mg/kg, s.c.) or vehicle (5% DMSO in saline) prior to stress binge testing. Immunohistochemistry was performed to assess both orexin levels in the lateral hypothalamus and Fos expression throughout the brain (Fos is a marker of neuronal activity). Results Immunohistochemistry revealed activation of lateral hypothalamic orexin neurons in stress binge mice compared to controls and a specific recruitment of orexin immunoreactive cells. Further, systemic antagonism of the orexin-1 receptor with SB-334867 reduced stress-induced binge eating. This effect was associated with reduced activation of the nucleus accumbens core, and increased activation of the bed nucleus of the stria terminalis (BNST) compared to vehicle-treated mice. Discussion & Conclusions Our data implicates orexin signaling through the orexin-1 receptor in stress-induced binge eating, likely via a network involving components of the limbic system (nucleus accumbens core and BNST). Further, our results indicate that repeated cycles of stress-induced binge eating recruit the orexin system (i.e. evidencing engagement of the orexin ‘reserve’). Hence, the orexin system may represent an exciting target for pharmacotherapeutic development.