The role of norepinephrine in differential response to stress in an animal model of XXXX .

@entity146 @entity19 @entity1005 @entity9830 @entity427 @entity130
BACKGROUND: @entity1005 ( @entity1005 ) is a prevalent @entity146 disorder precipitated by exposure to extreme traumatic stress. Yet, most individuals exposed to traumatic stress do not develop @entity1005 and may be considered psychologically resilient. The neural circuits involved in susceptibility or resiliency to @entity1005 remain unclear, but clinical evidence implicates changes in the noradrenergic system. METHODS: An animal model of @entity1005 called @entity130 Experience with Reminders of Stress (TERS) was developed by exposing C57BL/6 @entity19 to a single shock (2 mA, 10 sec) followed by exposure to six contextual 1-minute reminders of the shock over a 25-day period. @entity427 response (ASR) testing before the shock and after the last reminder allowed experimenters to separate the shocked @entity19 into two cohorts: @entity19 that developed a greatly increased ASR (TERS-susceptible @entity19 ) and @entity19 that did not (TERS-resilient @entity19 ). RESULTS: @entity146 and social behavioral correlates of @entity1005 increased in TERS-susceptible @entity19 but not in TERS-resilient @entity19 or control @entity19 . Characterization of @entity9830 expression in stress-related brain regions revealed that TERS-susceptible and TERS-resilient @entity19 displayed divergent brain activation following swim stress compared with control @entity19 . Pharmacological activation of noradrenergic inhibitory autoreceptors or blockade of postsynaptic a(1)-adrenoreceptors normalized ASR, @entity146 , and social interaction in TERS-susceptible @entity19 . The TERS-resilient, but not TERS-susceptible, @entity19 showed a trend toward decreased behavioral responsiveness to noradrenergic autoreceptor blockade compared with control @entity19 . CONCLUSIONS: These data implicate the noradrenergic system as a possible site of pathological and perhaps also adaptive plasticity in response to traumatic stress.
