Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa

Abstract

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive -running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals' wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity.

Cerebellar sub-divisions differ in exercise-induced plasticity of noradrenergic axons and in their association with resilience to activity-based anorexia

“…Each day, the body weight, food intake and WRA were measured prior to the onset of the dark cycle. WRA data were also collected automatically and continuously using the software of Med Associates (Chowdhury et al 2015).

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The Science Behind the Academy for Eating Disorders' Nine Truths About Eating Disorders

“…Controlled experiments have led to the development of animal models of hunger (Atasoy, Betley, Su, & Sternson, ) and binge eating (Murray, Tulloch, Chen, & Avena, ), providing evidence of neurobiological origins of eating disorders. In addition, an activity‐based anorexia (ABA) rodent model highlights increased physical activity and reduced body weight in response to restricted food access in animals (Chowdhury, Chen, & Aoki, ). Using neural circuit‐level approaches that enable activation or inhibition of anatomically and genetically defined brain pathways, like optogenetics and chemogenetics, multiple pathways that regulate different patterns of feeding behaviour have been identified (Hardaway, Crowley, Bulik, & Kash, ; Sternson & Roth, ) (see Table S7 for specific regions and nuclei).…”

Synaptic changes in the hippocampus of adolescent female rodents associated with resilience to anxiety and suppression of food restriction-evoked hyperactivity in an animal model for anorexia nervosa

“…Our lab has opted to use mice as well as rats as animal models, in preparation for future studies that will assess gene-based differences in ABA vulnerability (Aoki et al, 2012; Chowdhury et al, 2015a; Chowdhury et al, 2013). For both species, ABA is induced by first acclimating animals to the wheel for 4 days.…”

“…For mice, food access is limited to 2 hours per day (Fig. 3) (Chowdhury et al, 2015a). Within 24 hours of wheel access, rats and mice learn to ambulate on the wheel and exhibit voluntary wheel running.…”