Female WMI rats with genetic stress hyper-reactivity show enhanced
contextual fear memory without deficit in extinction of fear
Abstract
The prevalence of post-traumatic stress disorder is higher in females
than males, but pre-clinical models are established almost exclusively
in males. This study is aimed to investigate the Stress Enhanced Fear
Learning model of post-traumatic stress disorder in females. The model
mirrors post-traumatic stress disorder symptomology, whereby prior
stress leads to extinction resistant exaggerated contextual fear memory.
As stress-reactivity is highly relevant to the study and risk for
post-traumatic stress disorder, females of the stress hyper-reactive
Wistar Kyoto More Immobile (WMI) and its nearly isogenic control the
Wistar Kyoto Less Immobile (WLI) strains were employed. Adult females of
both strains were either not stressed or exposed to a two-hour restraint
stress, and 48 hours later underwent contextual fear conditioning. Fear
memory was measured 24 hours later, followed by extinction trials for a
week. Enhanced fear memory following contextual fear conditioning was
found in WMIs compared to WLI females and was neither exaggerated by
prior stress nor showed extinction deficit. The novel stressor of a
glucose challenge test resulted in subtle strain- and prior
stress-induced differences in plasma glucose and corticosterone
responses. Hippocampal expression levels of learning and memory related
genes, glucocorticoid receptor, estrogen receptors, and glucose
transporter 1, only changed in WLIs by prior stress. Taken together,
results indicate that stress hyper-reactive WMI females do not model
post-traumatic stress disorder using the stress enhanced fear learning
paradigm, and control WMI females are likely in a state of chronic
stress, as additional stressors produced no effects in most measures.