Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent Rats
Open Access
- 27 November 2020
- Vol. 12 (12), 3661
- https://doi.org/10.3390/nu12123661
Abstract
Intense physical activity and dieting are core symptoms of anorexia nervosa (AN). Their combination evolves into compulsivity, leading the patient into an out-of-control spiral. AN patients exhibit an altered activation of nucleus accumbens (NAc), revealing a dysfunctional mesocorticolimbic reward circuitry in AN. Since evidence exists that a dysregulation of the glutamate system in the NAc influences reward and taking advantage of the activity-based anorexia (ABA) rat model, which closely mimics the hallmarks of AN, we investigated the involvement of the glutamatergic signaling in the NAc in this experimental model. We here demonstrate that food restriction causes hyperactive and compulsive behavior in rodents, inducing an escalation of physical activity, which results in dramatic weight loss. Analysis of the glutamate system revealed that, in the acute phase of the pathology, ABA rats increased the membrane expression of GluA1 AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunits together with its scaffolding protein SAP97. Recovery of body weight reduced GluN2A/2B balance together with the expression of their specific scaffolding proteins, thus suggesting persistent maladaptive neurotransmission. Taken together, AMPA and NMDA (N-methyl-D-aspartate) receptor subunit reorganization may play a role in the motivational mechanisms underlying AN.This publication has 55 references indexed in Scilit:
- Role of the ventral striatum in developing anorexia nervosaTranslational Psychiatry, 2013
- Puberty as a critical risk period for eating disorders: A review of human and animal studiesHormones and Behavior, 2013
- Drug-evoked plasticity: do addictive drugs reopen a critical period of postnatal synaptic development?Frontiers in Molecular Neuroscience, 2012
- Quantitative analysis of AMPA receptor subunit composition in addiction-related brain regionsBrain Research, 2011
- Associations between specific components of compulsive exercise and eating‐disordered cognitions and behaviors among young womenInternational Journal of Eating Disorders, 2010
- Persistent hippocampal CA1 LTP in mice lacking the C-terminal PDZ ligand of GluR1Nature Neuroscience, 2005
- Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learningNeuroscience & Biobehavioral Reviews, 2004
- SAP102, a Novel Postsynaptic Protein That Interacts with NMDA Receptor Complexes In VivoNeuron, 1996
- Developmental and regional expression in the rat brain and functional properties of four NMDA receptorsNeuron, 1994
- Self-starvation of rats living in activity wheels on a restricted feeding schedule.Journal of Comparative and Physiological Psychology, 1967