Interacting Neural Processes of Feeding, Hyperactivity, Stress, Reward, and the Utility of the Activity-Based Anorexia Model of Anorexia Nervosa

Abstract

Anorexia nervosa (AN) is a psychiatric illness with minimal effective treatments and a very high rate of mortality. Understanding the neurobiological underpinnings of the disease is imperative for improving outcomes and can be aided by the study of animal models. The activity-based anorexia rodent model (ABA) is the current best parallel for the study of AN. This review describes the basic neurobiology of feeding and hyperactivity seen in both ABA and AN, and compiles the research on the role that stress-response and reward pathways play in modulating the homeostatic drive to eat and to expend energy, which become dysfunctional in ABA and AN.

Eat to Live or Live to Eat? The Neurobiology of Appetite Regulation

“…Two types of neurons, named after orexis (from Latin orexis [appetite] and Greek órexis [desire]), are housed here: orexigenic and anorexigenic neurons stimulate and suppress food-seeking behaviors, respectively. Arcuate nucleus neurons project to three other regions of the hypothalamus: the paraventricular nucleus, which influences several regions that promote catabolism (including the thyroid system, cortisol system, and oxytocin); the ventromedial hypothalamus, which suppresses feeding behavior through the release of brain-derived neurotrophic factor; and the lateral hypothalamus, which stimulates our search for calorically dense food and promotes locomotor activity through melanin-concentrating hormone and orexin (5,6). These three nuclei of the hypotha-lamus work together to ensure that we eat (or do not eat) based on the signals received about the body's current needs.…”

“…Leptin is produced in adipose tissue and acts on receptors in the arcuate nucleus to promote satiety and heat production (5). Ghrelin is produced in the gastrointestinal track, increases hunger, decreases energy expenditure, and stimulates cortisol release (5). Cortisol mobilizes glucose to ensure that the body has sufficient energy to respond to an acute stressor.…”

“…Cortisol mobilizes glucose to ensure that the body has sufficient energy to respond to an acute stressor. However, chronically elevated cortisol leads to a blunted leptin (satiety) response, increased desire for foods dense with sugar and fat (think comfort food), and the accumulation of abdominal fat (5,7). …”

“…Our pleasurable response to food largely overlaps with the brain's core reward circuits (e.g., as involved in drugs and sex). These include the amygdala, an area associated with emotional learning; the ventral tegmental area, which contains dopami-nergic neurons and signals motivation and reward seeking; the nucleus accumbens, centrally involved in reward learning; and the lateral hypothalamus, which coordinates these motivation signals and links the homeostatic system with the hedonic system (5). …”

“…Under ordinary circumstances, this might lead to increased food consumption. But these patients develop both an aberrant reward system and a so-called fear of food that causes them to overcome this drive to eat (5,10). As cortisol increases locomotor activity patients become hyperactive, which further burns calories.…”