Poster Presentation 4th Metabolic Diseases; Breakthrough Discoveries in Diabetes & Obesity Meeting 2024

Glutamatergic dysfunction in dorsal striatum underlies compulsive eating in an animal model of binge eating (#113)

Yan Li 1 , Diana Sketriene 1 , Cherry Mao 2 , Andrew J Lawrence 2 , Christina M Suhartono 1 , Nimshitha Manaph 1 , Robyn M Brown 1 2
  1. Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, VIC, Australia
  2. Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia

Purpose

Binge eating disorder is the most prevalent eating disorder and is associated with significant co-morbidities such as obesity. A hallmark feature of binge eating is a loss of control over eating insomuch that eating behaviour is compulsive in nature, persisting in the face of negative consequences. Disorders of compulsion are often associated with deficits in corticostriatal circuitry. Striatal glutamatergic dysfunction in particular is associated with addictive behaviour towards drugs of abuse. We used an intermittent access model of binge eating to determine whether similar glutamatergic deficits exist in an animal model of binge eating.

 

Methods

Rats were provided either continuous (ad libitum) or intermittent access to high-fat/high-sugar ‘western diet’ (30% kcal from fat) 1h x 3 per week in a stochastic nature for 8 weeks. A control group were provided access only to standard chow. A modified conditioned suppression test was used to measure the level of compulsive eating (i.e. eating despite the threat of a negative consequence). The dorsal striatum and nucleus accumbens were collected and processed to examine protein levels of various glutamate receptors and proteins associated with glutamatergic plasticity.

 

Results

Intermittent access ‘binge’ rats showed a decreased latency to start eating on the conditioned suppression test i.e. were more compulsive towards the high-fat/high-sugar food compared to rats that had continuous access or only access to standard chow. They also showed changes in glutamate receptors and proteins in the dorsal, not ventral striatum, synonymous with glutamate dysfunction observed in animal models of drug addiction in ventral striatum.

 

Conclusion

Collectively these data point to glutamatergic dysfunction in dorsal striatum as a mechanism underlying compulsive eating in binge eating disorder. These data also point to parallels in the neurobiology underlying binge eating disorder and substance use disorder. Lastly, this data suggests that sporadic and intermittent access to ‘junk food’ (even just 1h, 3 times per week) is sufficient to promote binge eating symptoms and associated neuroplastic changes.