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Submitted on August 18, 2005
Accepted on January 25, 2006
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CA, USA; Molecular and Integrative Neurosciences Department The Scripps Research Institute, La Jolla, CA, USA
* To whom correspondence should be addressed. E-mail: crivier{at}salk.edu.
Early life experiences can shape brain function and behavior in adulthood. The present study sought to elucidate the effects of repetitive, predictable vs. varied, unpredictable prenatal stress on sexually dichotomous neuroendocrine and anxiety-related behavioral responses in adult offspring. Rat dams were exposed repeatedly during the last week of pregnancy to no stress, only restraint stress [prenatal stress (PS)-restraint], or a randomized sequence of varied stressors (PS-random) and several behavioral and endocrine measures were assessed in adult male and female offspring. Repeated exposure to the same stressor (restraint) generated the most robust changes, including increased anxiety related behaviors (both passive, measured on the elevated plus maze, and active, measured using defensive burying tests), a delayed and prolonged HPA axis response to stress in female offspring. Conversely, PS-restraint males showed no changes in anxiety-like behavior and had elevated basal adrenocorticotropic hormone (ACTH) and a blunted HPA response to stress; consistent with attenuated HPA responsivity was an increase in GR immunoreactivity in the hippocampus, suggesting increased negative feedback upon the HPA axis in these animals. Prenatal exposure to a varied, unpredictable pattern of stressors did not have as much effect on HPA function, with most neuroendocrine measures residing intermediate to PS-restraint and control animals within each sex. Gonadal steroids were altered independent of the type of prenatal stress, but changes were only measurable in males (lower testosterone). The present data exemplify the differential sensitivity of the developing nervous and endocrine systems to stress, depending not only on gender but also on the nature of the stressful experience endured by the mother during pregnancy.
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