title: History of chronic stress modifies acute stress-evoked fear memory and acoustic startle in male rats.
abstract: Chronicity of trauma exposure plays an important role in the pathophysiology of posttraumatic stress disorder (PTSD). Thus, exposure to multiple traumas on a chronic scale leads to worse outcomes than acute events. The rationale for the current study was to investigate the effects of a single adverse event versus the same event on a background of chronic stress. We hypothesized that a history of chronic stress would lead to worse behavioral outcomes than a single event alone. Male rats (n = 14/group) were exposed to either a single traumatic event in the form of electric foot shocks (acute shock, AS), or to footshocks on a background of chronic stress (chronic variable stress-shock, CVS-S). PTSD-relevant behaviors (fear memory and acoustic startle responses) were measured following 7 d recovery. In line with our hypothesis, CVS-S elicited significant increases in fear acquisition and conditioning versus the AS group. Unexpectedly, CVS-S elicited reduced startle reactivity to an acoustic stimulus in comparison with the AS group. Significant increase in FosB/ΔFosB-like immunostaining was observed in the dentate gyrus, basolateral amygdala and medial prefrontal cortex of CVS-S rats. Assessments of neuropeptide Y (NPY), a stress-regulatory transmitter associated with chronic PTSD, revealed selective reduction in the hippocampus of CVS-S rats. Collectively, our data show that cumulative stress potentiates delayed fear memory and impacts defensive responding. Altered neuronal activation in forebrain limbic regions and reduced NPY may contribute to these phenomena. Our preclinical studies support clinical findings reporting worse PTSD outcomes stemming from cumulative traumatization in contrast to acute trauma.
authors.affiliation: Neuroscience Graduate Program, University of Cincinnati , Cincinnati, OH , USA .
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Schmeltzer
authors.forename: Lauren L
authors.initials: LL
authors.lastname: Vollmer
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Rush
authors.forename: Mychal
authors.initials: M
authors.lastname: Weinert
authors.forename: Charles M
authors.initials: CM
authors.lastname: Dolgas
authors.forename: Renu
authors.initials: R
authors.lastname: Sah
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D003213:Conditioning, Psychological; D018891:Dentate Gyrus / Q000378:metabolism; D005239:Fear; D008297:Male; D008568:Memory; D017397:Prefrontal Cortex / Q000378:metabolism; D016548:Prosencephalon; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D013216:Reflex, Startle / Q000502:physiology*; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology
chemical_list: C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos
keywords: Acute stress; PTSD; chronic stress; fear; hippocampus; neuropeptide Y