Prenatal maternal stress
increases the predisposition for affective disorders. Furthermore, women appear twice as likely as
men to develop stress- and depression-related disorders. Comparable behavioral changes
characteristic of clinical depression are found in rat offspring following prenatal stress (PS). These
include increased helplessness, altered anxiety indicators and sleep modifications. Our purpose was
to further investigate behavioral depression indices following PS as well as CNS structural changes
including sex specificity of these variables. Pregnant Sprague-Dawley rats were exposed to repeated
variable stress during days 13-21 of gestation. The PS paradigm consisted of two short-term
stressors during the day (e.g. restraint and forced swimming) and a long-term stressor overnight (e.g.
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fasting or lights on). We examined the rats at a young adult age for changes in locomotor activity,
depressive- and anxiety-like behavior as well as sleep architecture. Some animals were analyzed for
CNS microstructural changes based on diffusion MRI. Subsets of PS and control rats were exposed
to an acute stressor prior to the behavioral tests. Rearing/climbing activity in a familiar environment
(housing cage) increased at the end of the light and beginning of the dark phases in PS offspring
compared to controls. PS per se did not appear to change anxiety-like behavior in either sex.However, exposure to an acute stressor increased exploratory behavior in control animals and,
interestingly, PS blunted this effect. Relative and absolute numbers of rapid eye movement sleep
bouts were higher in PS offspring. Moreover, exposure to an acute stressor induced a REM rebound
effect in control animals but this compensatory mechanism was blunted in PS animals. Finally,
depression-like behavioral changes assessed in the forced swim test was selectively induced in PS
females. The central mechanisms mediating these differences may contribute to sex-specific
sensitivity to stressors and depression propensity in humans.