¹University of Melbourne, Department of Biochemistry and Pharmacology, Melbourne, Australia, ²Universitas Sebelas Maret, Department of Anatomy, Surakarta, Indonesia, ³Florey Institute of Neuroscience and Mental Health, Mental Health Division, Melbourne, Australia, ⁴University of Melbourne, The Florey Department of Neuroscience and Mental Health, Melbourne, Australia, ⁵Rutgers University, Department of Psychiatry and Rutgers Addiction Research Center, Piscataway, United States, ⁶University of Sydney, Brain and Mind Center and School of Psychology, Sydney, Australia, ⁷Monash University, Department of Surgery, Melbourne, Australia, ⁸Alfred Health, Department of Endocrinology and Diabetes, Melbourne, Australia

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.