Abstract
Repeated stressor exposure can sensitize physiological responses to novel stressors and facilitate the development of stress-related psychiatric disorders including anxiety. Disruptions in diurnal rhythms of sleep–wake behavior accompany stress-related psychiatric disorders and could contribute to their development. Complex stressors that include fear-eliciting stimuli can be a component of repeated stress experienced by human beings, but whether exposure to repeated fear can prime the development of anxiety and sleep disturbances is unknown. In the current study, adult male F344 rats were exposed to either control conditions or repeated contextual fear conditioning for 22 days followed by exposure to no, mild (10), or severe (100) acute uncontrollable tail shock stress. Exposure to acute stress produced anxiety-like behavior as measured by a reduction in juvenile social exploration and exaggerated shock-elicited freezing in a novel context. Prior exposure to repeated fear enhanced anxiety-like behavior as measured by shock-elicited freezing, but did not alter social exploratory behavior. The potentiation of anxiety produced by prior repeated fear was temporary; exaggerated fear was present 1 day but not 4 days following acute stress. Interestingly, exposure to acute stress reduced rapid eye movement (REM) and non-REM (NREM) sleep during the hours immediately following acute stress. This initial reduction in sleep was followed by robust REM rebound and diurnal rhythm flattening of sleep/wake behavior. Prior repeated fear extended the acute stress-induced REM and NREM sleep loss, impaired REM rebound, and prolonged the flattening of the diurnal rhythm of NREM sleep following acute stressor exposure. These data suggest that impaired recovery of sleep/wake behavior following acute stress could contribute to the mechanisms by which a history of prior repeated stress increases vulnerability to subsequent novel stressors and stress-related disorders.
Highlights
Acute activation of the stress response evolved to enhance chances of survival, excessive, chronic, or repeated activation of the stress response can negatively impact central and peripheral physiological systems [1,2,3] and is a significant risk factor for the development of stress-related mental illness including depression, anxiety, and post-traumatic stress disorder [PTSD; [4,5,6]]
We have previously reported that repeated exposure to fear conditioning can sensitize physiological responses to acute uncontrollable stress and exacerbate uncontrollable stress-induced disruptions in diurnal rhythms of heart rate (HR) and core body temperature (CBT) [18]
Here, we report that prior exposure to a repeated emotional stressor can increase anxiety-like behavior and induce prolonged sleep disruption following exposure to a subsequent acute, novel stressor
Summary
Acute activation of the stress response evolved to enhance chances of survival, excessive, chronic, or repeated activation of the stress response can negatively impact central and peripheral physiological systems [1,2,3] and is a significant risk factor for the development of stress-related mental illness including depression, anxiety, and post-traumatic stress disorder [PTSD; [4,5,6]]. Rodents exposed to repeated stressors can display exaggerated hormonal [14,15,16], autonomic [17, 18] and neuronal [19, 20], responses to acute, novel stressors. These exaggerated responses to novel stressors in rodents can occur concordantly with the development of anxietyand depression-like behaviors [21, 22]. Disturbed slow wave [33] and REM [34,35,36,37] sleep is considered a hallmark symptom [38] and post-trauma predictor [39] of PTSD
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