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Relation between corticosterone and fear‐related behavior in mice selectively bred for high or low alcohol preference
Author(s) -
Chester Julia A.,
Kirchhoff Aaron M.,
Barrenha Gustavo D.
Publication year - 2014
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12034
Subject(s) - corticosterone , fear conditioning , mifepristone , medicine , endocrinology , conditioning , glucocorticoid , psychology , extinction (optical mineralogy) , antagonist , conditioned place preference , freezing behavior , receptor , chemistry , biology , hormone , amygdala , pregnancy , statistics , mineralogy , mathematics , genetics
Abstract Blunted cortisol responses to stress or trauma have been linked with genetic (familial) risk for both alcoholism and post‐traumatic stress disorder ( PTSD ). Mouse lines selectively bred for high ( HAP ) or low ( LAP ) alcohol preference may be a relevant model of genetic risk for co‐morbid alcoholism and PTSD in humans. HAP mice show greater fear‐potentiated startle ( FPS ), a model used to study PTSD , than LAP mice. The relation between corticosterone ( CORT ) and FPS behavior was explored in four experiments. Naïve male and female HAP 2 and LAP 2 mice received fear‐conditioning or control treatments, and CORT levels were measured before and immediately after fear‐conditioning or FPS testing. In two other experiments, HAP 2 mice received CORT (1.0, 5.0 or 10.0 mg/kg) or a glucocorticoid receptor antagonist (mifepristone; 25.0 and 50.0 mg/kg) 30 minutes before fear conditioning. HAP 2 mice exposed to fear conditioning and to control foot shock exposures showed lower CORT after the fear‐conditioning and FPS testing sessions than LAP 2 mice. A trend toward higher FPS was seen in HAP 2 mice pretreated with 10.0 mg/kg CORT , and CORT levels were the lowest in this group, suggesting negative feedback inhibition of CORT release. Mifepristone did not alter FPS . Overall, these results are consistent with data in humans and rodents indicating that lower cortisol/ CORT levels after stress are associated with PTSD / PTSD ‐like behavior. These findings in HAP 2 and LAP 2 mice suggest that a blunted CORT response to stress may be a biological marker for greater susceptibility to develop PTSD in individuals with increased genetic risk for alcoholism.