Abstract
Stress plays a key role in the development of psychiatric disorders and has a negative impact on sleep integrity. In mice, chronic social defeat stress (CSDS) is an ethologically valid model of stress-related disorders but little is known about its effects on sleep regulation. Here, we investigated the immediate and long-term effects of 10 consecutive days of social defeat (SD) on vigilance states in C57Bl/6J male mice. Social behavior was assessed to identify susceptible mice, i.e., mice that develop long-lasting social avoidance, and unsusceptible mice. Sleep-wake stages in mice of both groups were analyzed by means of polysomnographic recordings at baseline, after the first, third, and tenth stress sessions and on the 5th recovery day (R5) following the 10-day CSDS. In susceptible mice, each SD session produced biphasic changes in sleep-wake states that were preserved all along 10-day CSDS. These sessions elicited a short-term enhancement of wake time while rapid eye-movement (REM) sleep was strongly inhibited. Concomitantly, delta power was increased during non REM (NREM) sleep. During the following dark period, an increase in total sleep time, as well as wake fragmentation, were observed after each analyzed SD session. Similar changes were observed in unsusceptible mice. At R5, elevated high-frequency EEG activity, as observed in insomniacs, emerged during NREM sleep in both susceptible and unsusceptible groups suggesting that CSDS impaired sleep quality. Furthermore, susceptible but not unsusceptible mice displayed stress-anticipatory arousal during recovery, a common feature of anxiety disorders. Altogether, our findings show that CSDS has profound impacts on vigilance states and further support that sleep is tightly regulated by exposure to stressful events. They also revealed that susceptibility to chronic psychological stress is associated with heightened arousal, a physiological feature of stress vulnerability.
Highlights
Mental disorders are a health priority as they are among the major contributors to the global burden of disease due to their high prevalence and high disability (Whiteford et al, 2013; Trautmann et al, 2016)
The present study examined sleep-wake patterns and sleep architecture of mice exposed to chronic social defeat stress (CSDS)
Exposure to acute social defeat (SD) stress during the sleep phase produced on defeated mice of both the susceptible and the unsusceptible subgroups a temporally dual effect on sleep that initially involved sustained wake and sleep loss with suppression of rapid eyemovement (REM) sleep
Summary
Mental disorders are a health priority as they are among the major contributors to the global burden of disease due to their high prevalence and high disability (Whiteford et al, 2013; Trautmann et al, 2016). Taken altogether, polysomnographic studies conducted in patient with depression and PTSD have yielded contradictory results, in particular for REM sleep, highlighting the complexity of using sleep biomarkers in these diseases (as described in the following reviews: Pillar et al, 2000; Buysse et al, 2006; Armitage, 2007; Germain, 2013 and for an overview see the following metaanalysis reports: Benca et al, 1992; Kobayashi et al, 2007; Pillai et al, 2011; Baglioni et al, 2016) These conflicting findings may be due to confounding factors, analysis done at different stages of the illness, disease heterogeneity, and comorbidities with other psychiatric conditions. Polysomnographic and quantitative EEG, the objective gold standard methods for sleep assessment, are carried out and analyzed with the same methods in both humans and animals
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