Sex differences in stress-induced sleep deficits.

Sleep disruptions are hallmarks in the pathophysiology of several stress-related disorders, including Major Depressive Disorder (MDD) and Post-Traumatic Stress Disorder (PTSD), both known to disproportionately affect female populations. Although previous studies have attempted to investigate disordered sleep in women, few studies have explored and compared how repeated stress affects sleep in both sexes in either human or animal models. We have previously shown that male rats exhibit behavioral and neuroendocrine habituation to 5 days of repeated restraint, whereas females do not; additional days of stress exposure are required to observe habituation in females. This study examined sex differences in sleep measures prior to, during, and after repeated restraint stress in adult male and female rats. Our data reveal that repeated stress increased time spent awake and decreased slow-wave sleep (SWS) and REM sleep (REMS) in females, and these effects persisted over 2 days of recovery. In contrast, the effects of stress on males were transient. These insomnia-like symptoms were accompanied by a greater number of exaggerated motor responses to waking from REMS in females, a phenotype similar to trauma-related nightmares. In sum, these data demonstrate that repeated stress produces disruptions in sleep that persist days after the stress is terminated in female rats. These disruptions in sleep produced by 5 days of repeated restraint may be due to their lack of habituation.