Identifying Predictors of Activity Based Anorexia Susceptibility in Diverse Genetic Rodent Populations

Abstract

Animal studies are very useful in detection of early disease indicators and in unravelling the pathophysiological processes underlying core psychiatric disorder phenotypes. Early indicators are critical for preventive and efficient treatment of progressive psychiatric disorders like anorexia nervosa. Comparable to physical hyperactivity observed in anorexia nervosa patients, in the activity-based anorexia rodent model, mice and rats express paradoxical high voluntary wheel running activity levels when food restricted. Eleven inbred mouse strains and outbred Wistar WU rats were exposed to the activity-based anorexia model in search of identifying susceptibility predictors. Body weight, food intake and wheel running activity levels of each individual mouse and rat were measured. Mouse strains and rats with high wheel running activity levels during food restriction exhibited accelerated body weight loss. Linear mixed models for repeated measures analysis showed that baseline wheel running activity levels preceding the scheduled food restriction phase strongly predicted activity-based anorexia susceptibility (mice: Beta = −0.0158 (±0.003 SE), P<0.0001; rats: Beta = −0.0242 (±0.004 SE), P<0.0001) compared to other baseline parameters. These results suggest that physical activity levels play an important role in activity-based anorexia susceptibility in different rodent species with genetically diverse background. These findings support previous retrospective studies on physical activity levels in anorexia nervosa patients and indicate that pre-morbid physical activity levels could reflect an early indicator for disease severity.

Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats

“…The best predictive model was a combination of RW activity during ad-libitum feeding, SPA and body weight history (Figures 4 and 5). Previous studies of ABA susceptibility showed that RW activity is a strong predictor of body weight loss during ABA in female rats [18, 25, 26]. Our results add support to the hypothesis that RW activity during ad-libitum feeding has predictive value for body weight changes during ABA in female rats and extend this result to male rats (Figure 4 and 5).…”

“…All these parameters, except SPA and stereotypic behavior, have been suggested to predict severity of weight loss during ABA in other studies [25-27]. …”

“…There is large variability between mouse strains in body weight loss during ABA [18, 24, 25]. Studies in female mice and rats indicate that RW activity during ad-libitum feeding predicts body weight loss during ABA [25, 26]. In female rats, locomotor activity (measured by telemetry) during RW exposure with ad-libitum feeding is a predictor of body weight loss during ABA [25].…”

“…Studies in female mice and rats indicate that RW activity during ad-libitum feeding predicts body weight loss during ABA [25, 26]. In female rats, locomotor activity (measured by telemetry) during RW exposure with ad-libitum feeding is a predictor of body weight loss during ABA [25]. These studies support the idea that RW activity can predict ABA susceptibility, consistent with RW as a model of voluntary exercise [27] and its putative role as a cause and symptom of AN.…”

Anorexia nervosa as a motivated behavior: Relevance of anxiety, stress, fear and learning

“…In this paradigm, when food access is restricted in the presence of a running wheel, animals paradoxically increase their exercise, consume less food than sedentary controls and lose more weight, running themselves to death within a few weeks. There is individual vulnerability in susceptibility to ABA, but young female rats with higher activity levels at baseline tend to eat the least, run the most, and lose the most weight [68][69][70], consistent with the clinical observation in AN that excessive exercise often precedes dieting and escalates with weight loss [71,72]. Excessive exercise has long been recognized as a hallmark of AN [73], is present in up to 80% of cases and appears to play a central role in the pathogenesis and progression of the disorder [74].…”