Impaired reversal learning in an animal model of anorexia nervosa

Background: Clinical investigations indicate that anorexia nervosa (AN) is associated with impaired cognitive flexibility. Activity-based anorexia (ABA), a rodent behavioral model of AN, is characterized by compulsive wheel running associated with voluntary food restriction and progressive weight loss. The goal of this study was to test whether ABA is associated with impaired cognitive flexibility. Methods: Female Sprague-Dawley rats were trained to perform the attentional set-shifting test (ASST) to assess cognitive flexibility, including capacity for set-shifting and reversal learning. Rats were assigned to ABA or weight-loss paired control (WPC) conditions. Following baseline testing, the ABA group had access to food for 1 h/d and access to running wheels 23 h/d until 20% weight loss was voluntarily achieved. For the WPC group, running wheels were locked and access to food was restricted to reduce body weight at the same rate as the ABA group. ASST performance was assessed after weight loss, and again following weight recovery. Results: Compared to baseline, the ABA group (but not the WPC group) showed a significant decrement in reversal learning at low weight, with return to baseline performance following weight restoration. The other components of ASST were not affected. Conclusions: Impaired reversal learning, indicative of increased perseverative responding, in the ABA model reveals its potential to recapitulate selective components of cortical dysfunction in AN. This finding supports the utility of the ABA model for investigations of the neural mechanisms underlying such deficits. Reversal learning relies on neural circuits involving the orbitofrontal cortex and thus the results implicate orbitofrontal abnormalities in AN-like state.