Journal
BRAIN RESEARCH
Volume 1654, Issue -, Pages 102-115Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2016.01.019
Keywords
Activity-based anorexia; Extrasynaptic; GABA; Dendritic spines; Hippocampus; Food restriction; Exercise; Adolescence; Neurolucida; Sholl analysis; Anxiety; Wheel running activity; Apical dendrites; Tetrahydroprogesterone; Glutamic acid decarboxylase; Electron microscopy; Immunocytochemistry; Hyperactivity
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Funding
- Klarman Family Foundation Grant Program in Eating Disorders Research
- National Institutes of Health [R21MH091445-01, R21MH105846, R01NS066019-01A1, R25GM097634-01, R01NS047557-07A1]
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Anorexia nervosa is a mental illness that emerges primarily during early adolescence, with mortality rate that is 200 times higher than that of suicide. The illness is characterized by intense fear of gaining weight, heightened anxiety, obstinate food restriction, often accompanied by excessive exercise, in spite of mounting hunger. The illness affects females nine times more often than males, suggesting an endocrine role in its etiology. Its relapse rate exceeds 25%, yet there are no accepted pharmacological treatments to prevent this. Here, we summarize studies from this laboratory that have used adolescent female rodents in activity-based anorexia (ABA), an animal model of anorexia nervosa, with the goal of identifying neurobiological underpinnings of this disease. We put forth a hypothesis that a GABAergic mechanism within the hippocampus is central to regulating an individual's anxiety which, in turn, strongly influences the individual's resilience/vulnerability to ABA. In particular, we propose that ionotropic GABAA receptors containing the subunits alpha4 and delta, are at play for exerting shunting inhibition upon hippocampal pyramidal neurons that become more excitable during ABA. Since these receptors confer insensitivity to benzodiazepines, this pharmacological profile of ABA fits with lack of report indicating efficacy of benzodiazepines in reducing the anxiety experienced by individuals with anorexia nervosa. The idea that the GABAergic system of the hippocampus regulates resilience/vulnerability to anorexia nervosa complements current opinions about the important roles of the prefrontal cortex, amygdala, striatum, gustatory pathways and feeding centers of the hypothalamus and of the neuromodulators, serotonin and dopamine, in the etiology of the disease. This article is part of a Special Issue entitled SI: Adolescent plasticity. (C) 2016 Elsevier B.V. All rights reserved.
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