TY - JOUR
T1 - Differential effects of glucocorticoid and mineralocorticoid antagonism on anxiety behavior in mild traumatic brain injury
AU - Fox, Laura C.
AU - Davies, Daniel R.
AU - Scholl, Jamie L.
AU - Watt, Michael J.
AU - Forster, Gina L.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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 (20 mg/kg) or spironolactone (50 mg/kg) to block glucocorticoid and mineralocorticoid receptors, respectively, 40 min 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.
AB - 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 (20 mg/kg) or spironolactone (50 mg/kg) to block glucocorticoid and mineralocorticoid receptors, respectively, 40 min 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.
KW - Anxiety
KW - Glucocorticoids
KW - Mild traumatic brain injury
KW - Rat
KW - Stress
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U2 - 10.1016/j.bbr.2016.06.048
DO - 10.1016/j.bbr.2016.06.048
M3 - Article
C2 - 27363926
AN - SCOPUS:84978036302
VL - 312
SP - 362
EP - 365
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
ER -