Evaluating anhedonia in the activity-based anorexia (ABA) rat model

Abstract

Patients suffering anorexia nervosa (AN) become anhedonic, in other words, unable or unwilling to derive normal pleasures and avoid rewarding outcomes, most profoundly in food intake. The neurobiological underpinnings of anhedonia are likely to involve mesolimbic reward circuitry. We propose here that this circuitry and its involvement in AN can be investigated using the activity-based anorexia (ABA) rodent model that recapitulates many of the characteristics of the human condition, most notably rapid weight loss. Preference for sweetened water was used to assay hedonic processing in female Sprague-Dawley rats exposed to the ABA protocol, which involves free access to running wheels paired with time-limited access to food. This protocol uncovered a transient anhedonia in only one quarter of cases; however, exposure to running wheels alone was associated with a rapid aversion to sweetened water (F1.833, 20.17 = 78.29, p < .0001), and time-limited food access alone did not impact preference (F2.205, 24.25 = 0.305, p = .761). High levels of running wheel activity prior to the onset of food restriction increased susceptibility to body weight loss in ABA (F10,196.129 = 2.069, p = .029) and food anticipatory activity predicted subsequent food intake only for rats that were resistant to body weight loss (r = 0.44, p = .001). These data are inconsistent with the hypothesis that anhedonia underscores the precipitous weight loss in ABA, however, they highlight the predictive nature of hyperactivity in susceptibility to the ABA paradigm. These results will help inform the neurobiological framework of ABA and provide insight into the mechanisms of reward relevant to feeding and weight loss.