Activity-based anorexia animal model: a review of the main neurobiological findings

Background: The genesis of anorexia nervosa (AN), a severe eating disorder with a pervasive effect on many brain functions such as attention, emotions, reward processing, cognition and motor control, has not yet been understood. Since our current knowledge of the genetic aspects of AN is limited, we are left with a large and diversified number of biological, psychological and environmental risk factors, called into question as potential triggers of this chronic condition with a high relapse rate. One of the most valid and used animal models for AN is the activity-based anorexia (ABA), which recapitulates important features of the human condition. This model is generated from naïve rodents by a self-motivated caloric restriction, where a fixed schedule food delivery induces spontaneous increased physical activity. Aim: In this review, we sought to provide a summary of the experimental research conducted using the ABA model in the pursuit of potential neurobiological mechanism(s) underlying AN. Method: The experimental work presented here includes evidence for neuroanatomical and neurophysiological changes in several brain regions as well as for the dysregulation of specific neurochemical synaptic and neurohormonal pathways. Results: The most likely hypothesis for the mechanism behind the development of the ABA phenotype relates to an imbalance of the neural circuitry that mediates reward processing. Evidence collected here suggests that ABA animals show a large set of alterations, involving regions whose functions extend way beyond the control of reward mechanisms and eating habits. Hence, we cannot exclude a primary role of these alterations from a mechanistic theory of ABA induction. Conclusions: These findings are not sufficient to solve such a major enigma in neuroscience, still they could be used to design ad hoc further experimental investigation. The prospect is that, since treatment of AN is still challenging, the ABA model could be more effectively used to shed light on the complex AN neurobiological framework, thus supporting the future development of therapeutic strategies but also the identification of biomarkers and diagnostic tools. Plain English summary: Anorexia Nervosa (AN) is a severe eating disorder with a dramatic effect on many functions of our brain, such as attention, emotions, cognition and motion control. Since our current knowledge of the genetic aspects behind the development of AN is still limited, many biological, psychological and environmental factors must be taken into account as potential triggers of this condition. One of the most valid animal models for studying AN is the activity-based anorexia (ABA). In this model, rodents spontaneously limit food intake and start performing increased physical activity on a running wheel, a result of the imposition of a fixed time schedule for food delivery. In this review, we provide a detailed summary of the experimental research conducted using the ABA model, which includes extended evidence for changes in the anatomy and function of the brain of ABA rodents. The hope is that such integrated view will support the design of future experiments that will shed light on the complex brain mechanisms behind AN. Such advanced knowledge is crucial to find new, effective strategies for both the early diagnosis of AN and for its treatment.