The Rise and Fall of Dopamine: A Two-Stage Model of the Development and Entrenchment of Anorexia Nervosa.

Jeff A Beeler,Nesha S Burghardt

doi:10.3389/fpsyt.2021.799548

Abstract

Dopamine has long been implicated as a critical neural substrate mediating anorexia nervosa (AN). Despite nearly 50 years of research, the putative direction of change in dopamine function remains unclear and no consensus on the mechanistic role of dopamine in AN has been achieved. We hypothesize two stages in AN– corresponding to initial development and entrenchment– characterized by opposite changes in dopamine. First, caloric restriction, particularly when combined with exercise, triggers an escalating spiral of increasing dopamine that facilitates the behavioral plasticity necessary to establish and reinforce weight-loss behaviors. Second, chronic self-starvation reverses this escalation to reduce or impair dopamine which, in turn, confers behavioral inflexibility and entrenchment of now established AN behaviors. This pattern of enhanced, followed by impaired dopamine might be a common path to many behavioral disorders characterized by reinforcement learning and subsequent behavioral inflexibility. If correct, our hypothesis has significant clinical and research implications for AN and other disorders, such as addiction and obesity.

Highlights

Specialty section: This article was submitted to Molecular Psychiatry, a section of the journal Frontiers in Psychiatry
Chronic self-starvation reverses this escalation to reduce or impair dopamine which, in turn, confers behavioral inflexibility and entrenchment of established anorexia nervosa (AN) behaviors. This pattern of enhanced, followed by impaired dopamine might be a common path to many behavioral disorders characterized by reinforcement learning and subsequent behavioral inflexibility
We propose a two-stage model of AN in which opposite changes in dopamine function underlie each stage of the disorder: initial emergence and establishment of AN behaviors, and subsequent entrenchment of an established AN behavioral regimen

Summary

Introduction

Specialty section: This article was submitted to Molecular Psychiatry, a section of the journal Frontiers in Psychiatry. Caloric restriction, when combined with exercise, triggers an escalating spiral of increasing dopamine that facilitates the behavioral plasticity necessary to establish and reinforce weight-loss behaviors. We propose a two-stage model of AN in which opposite changes in dopamine function underlie each stage of the disorder: initial emergence and establishment of AN behaviors, and subsequent entrenchment of an established AN behavioral regimen.

Results

Conclusion