Rethinking the Approach to Preclinical Models of Anorexia Nervosa

The goal of this review is to describe how emerging technological developments in pre-clinical animal research can be harnessed to accelerate research in anorexia nervosa (AN).

The activity-based anorexia (ABA) paradigm, the best characterized animal model of AN, combines restricted feeding, excessive exercise, and weight loss. A growing body of evidence supports the idea that pathophysiological weight loss in this model is due to cognitive inflexibility, a clinical feature of AN. Targeted manipulations that recapitulate brain changes reported in AN - hyperdopaminergia or hyperactivity of cortical inputs to the nucleus accumbens - exacerbate weight loss in the ABA paradigm, providing the first evidence of causality. The power of preclinical research lies in the ability to assess the consequences of targeted manipulations of neuronal circuits that have been implicated in clinical research. Additional paradigms are needed to capture other features of AN that are not seen in ABA.