The ability of stress to alter sleep in mice is sensitive to reproductive hormones

Abstract Though stress causes complex sleep disruptions that are different in females and males, little is known about how sex influences the ability of stress to alter sleep. To date there have been no comprehensive examinations of whether effects of stress on sleep are sensitive to determinants of sex, such as reproductive hormones. Since restraint stress produces a sexually dimorphic increase in rapid eye movement sleep (REMS) amount in mice that is greater in males than females, in the current study we sought to determine whether estrogens and androgens influence the ability of restraint stress to alter sleep states. We removed the gonads from adult female and male C57BL/6J mice and implanted the mice with recording electrodes to monitor sleep–wake states. Gonadectomized females and males exhibited similar amounts of REMS in response to restraint stress. Mice were then implanted with continuous release hormone pellets. Females received 17β-estradiol and males received testosterone. Hormone replacement (HR) in females decreased the REMS response to restraint stress while HR in males increased the REMS response to restraint stress. The combined effects of HR in females and males restored the sex difference in the ability of restraint stress to alter REMS. These results demonstrate that sex differences in the effects of stress on REMS are dependent on reproductive hormones and support the view that endogenous or exogenous changes in the reproductive hormone environment influence sleep responses to stress.