Fear and food: Anxiety‐like behavior and the susceptibility to weight loss in an activity‐based anorexia rat model

Abstract

Anorexia nervosa (AN) is a severe psychiatric disorder characterized by energy restriction, low body weight, a fear of gaining weight, and often excessive physical activity. Anxiety disorders appear to constitute a major risk factor for developing AN and are the most frequent comorbidity. Here, the influence of anxiety‐like behavior prior to food restriction on increased physical activity, leading to greater susceptibility to weight loss, was tested in rats. Furthermore, the possible anxiolytic effect of starvation itself was analyzed. A chronic starvation model activity‐based anorexia (ABA) was applied to mimic physiological and behavioral characteristics of AN. During the induction of starvation and acute starvation, food intake was reduced by 70% and the rats lost 25% of their body weight, which was kept stable to imitate chronic starvation. Anxiety‐like behavior was quantified before and after chronic starvation using the elevated plus maze, based on rodents’ aversion to open spaces. Anxiety‐related behavior before food restriction was associated with increased running‐wheel activity during habituation and during the induction of starvation, and predicted faster weight loss in ABA rats. Additionally, food‐restricted animals showed less anxiety‐like behavior after chronic starvation. Animals showing more anxiety‐like behavior appear to be more susceptible to weight loss, partially mediated by increased physical activity. Anxiety‐related behavior was associated with increased physical activity, which in turn was associated with more rapid weight loss. Our data let us assume that food restriction has an anxiolytic effect. These findings demonstrate the importance of considering anxiety disorders in patients with AN.

The Role of Glial Cells in Regulating Feeding Behavior: Potential Relevance to Anorexia Nervosa

“…The described changes on the cellular level are paralleled with behavioral deficits shown in ABA rodents, e.g., impaired memory performance in the novel object recognition (NOR) task [ 119 ] and reduced anxiety-like behavior in the elevated plus-maze test [ 120 , 121 ]. The impairment of NOR memory was reversed following administration of anti-NPY antiserum, Y5 receptor antagonist CPG71683, and anti-AgRP antibody connecting this behavior task with hypothalamic neuronal circuits [ 122 ].…”

Long-lasting BDNF signaling alterations in the amygdala of adolescent female rats exposed to the activity-based anorexia model

“…In fact, the body weight loss of ABA rodents was much greater than the body weight loss of animals exposed to food restriction only, which was also accompanied by an exponential increase in physical activity within 48 h from the beginning of the caloric restriction. The out-of-control behavior that drives rodents to run instead of feeding has been associated with increased anxiety-like behavior both in rodents and in humans, constituting a potential risk factor for more rapid weight loss (Holtkamp et al, 2004 ; Kaye et al, 2004 ; Wable et al, 2015 ; Schwenzer et al, 2022 ). In addition, higher hyperactivity in the clinic has been linked to a worse prognosis (Scheurink et al, 2010 ) and to high level of comorbidity with anxiety and depression (Penas-Lledo et al, 2002 ; Shroff et al, 2006 ).…”

Current Discoveries and Future Implications of Eating Disorders

“…Anti-anxiety medications help anorectics to comply with nutritional rehabilitation programs [85,86].…”