title: Differential effects of glucocorticoid and mineralocorticoid antagonism on anxiety behavior in mild traumatic brain injury.
abstract: Mild traumatic brain injuries (TBIs) comprise three-quarters of all TBIs occurring in the United States annually, and psychological symptoms arising from them can last years after injury. One commonly observed symptom following mild TBI is generalized anxiety. Most mild TBIs happen in stressful situations (sports, war, domestic violence, etc.) when glucocorticoids are elevated in the brain at the time of impact, and glucocorticoids have negative effects on neuronal health following TBI. Therefore, blocking glucocorticoid receptors might prevent emergence of anxiety symptoms post-injury. Adult male rats received mifepristone (20mg/kg) or spironolactone (50mg/kg) to block glucocorticoid and mineralocorticoid receptors, respectively, 40min prior to being exposed to acute social defeat stress followed immediately by mild TBI. In defeated rats with concomitant mild TBI, mifepristone restored time spent in the open arms of an elevated plus maze to control levels, demonstrating for the first time that glucocorticoid receptors play a critical role in the development of anxiety after mild TBI. Future treatments could target these receptors, alleviating anxiety as a major side effect in victims of mild TBI sustained in stressful situations.
authors.affiliation: Center for Brain and Behavior Research, University of South Dakota, Sanford School of Medicine, Division of Basic Biomedical Sciences, 414 East Clark St, Vermillion, SD, United States. Electronic address: laura.fox@usd.edu.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Fox
authors.affiliation: Center for Brain and Behavior Research, University of South Dakota, Sanford School of Medicine, Division of Basic Biomedical Sciences, 414 East Clark St, Vermillion, SD, United States. Electronic address: Daniel.davies@coyotes.usd.edu.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Davies
authors.affiliation: Center for Brain and Behavior Research, University of South Dakota, Sanford School of Medicine, Division of Basic Biomedical Sciences, 414 East Clark St, Vermillion, SD, United States. Electronic address: Jamie.Scholl@usd.edu.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Scholl
authors.affiliation: Center for Brain and Behavior Research, University of South Dakota, Sanford School of Medicine, Division of Basic Biomedical Sciences, 414 East Clark St, Vermillion, SD, United States. Electronic address: Mick.Watt@usd.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Watt
authors.affiliation: Center for Brain and Behavior Research, University of South Dakota, Sanford School of Medicine, Division of Basic Biomedical Sciences, 414 East Clark St, Vermillion, SD, United States. Electronic address: gforster@usd.edu.
authors.forename: Gina L
authors.initials: GL
authors.lastname: Forster
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D001924:Brain Concussion / Q000150:complications / Q000503:physiopathology*; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors* / Q000502:physiology*; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D013148:Spironolactone / Q000008:administration & dosage; D013315:Stress, Psychological / Q000503:physiopathology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D015735:Mifepristone
keywords: Anxiety; Glucocorticoids; Mild traumatic brain injury; Rat; Stress