The Impact of Stress and Anxiety on Eating Disorders
Post by Baldomero B. Ramirez Cantu
The takeaway
Stress causes anxiety-prone female mice to prefer a starvation-like state highlighting the potential neural mechanisms linking stress, anxiety and anorexia nervosa.
What's the science?
Eating disorders, such as anorexia nervosa, are severe psychiatric conditions marked by self-imposed starvation. Despite their complex etiology, characterized by a combination of genetic, environmental, and psychological factors, effective treatments remain limited. Experimental models in rodents have provided insights into underlying neural mechanisms but often fail to capture the crucial aspect of volitional starvation seen in patients. In a recent study published in Neuron, Kucukdereli et al., investigated how repeated stress influences the voluntary seeking of a starvation-like state in mice. Their findings offer an insight into the role of stress-induced anxiety in driving behaviors akin to anorexia nervosa.
How did they do it?
To investigate the role of stress in voluntary seeking of a starvation-like state, researchers developed a virtual reality (VR) real-time place preference protocol for head-fixed mice. Male and female mice were then exposed to two distinct virtual corridors paired with either optogenetic stimulation of agouti-related peptide (AgRP) hypothalamic neurons or a neutral outcome.
Optogenetic stimulation was achieved using a transgenic approach, involving the expression of light-activated channelrhodopsin (ChR2) in AgRP neurons, activated via an optic fiber placed above the arcuate nucleus.
The experimental VR protocol included conditioning sessions where mice were alternately exposed to the stimulation or neutral corridor, followed by real-time place preference sessions where mice were allowed to choose between the two corridors. To test the hypothesis that stress influences AgRP neuron stimulation preference, researchers introduced repeated stressors by delivering unpredictable tail shocks during conditioning sessions.
Anxiety-like behavior was assessed using open-field tests (OFTs) before and after the stress exposure sessions to confirm effective stress induction. A preference index was calculated based on the duration mice dwelled in the stimulation corridor, excluding bouts of locomotion. Additionally, elevated plus maze (EPM) assays were conducted before the experiments to measure baseline anxiety levels, helping to identify any pre-existing stress-related traits in the mice.
What did they find?
Before stress exposure, male mice generally exhibited a mild aversion to AgRP neuron stimulation, suggesting that the induced starvation-like state was aversive. Female mice showed no consistent preference or aversion to AgRP stimulation, with individual responses varying.
Following repeated stress exposure through unpredictable tail shocks during conditioning sessions, female mice displayed significant changes in behavior. A subset of females developed a strong preference for AgRP stimulation, actively seeking the starvation-like state, while others exhibited increased aversion. In contrast, male mice showed a reduction in aversion to AgRP stimulation but did not develop a preference for it.
Analysis of baseline anxiety levels, measured using the EPM assay, revealed that female mice with higher anxiety scores were more likely to prefer AgRP stimulation after stress exposure. This correlation was not observed in male mice, indicating that predisposition to anxiety significantly influenced the behavioral response to stress in females.
These results demonstrate a pronounced sex difference in how stress affects the seeking of a starvation-like state, with female mice showing more variability based on their anxiety levels. This suggests that individual susceptibility to stress-induced anxiety plays a crucial role in behaviors associated with conditions such as anorexia nervosa.
What's the impact?
This research provides valuable insights into the complex interplay between stress, anxiety, and behaviors resembling those seen in anorexia nervosa. These findings may inform future studies on the neurobiological mechanisms underlying eating disorders and potentially guide the development of targeted pharmacological and behavioral interventions that consider stress management and anxiety reduction strategies