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8 ball pool game., E.K., D.M., S.K., B.S., Y.C., H.M., and A.N. designed and organized the database. All authors contributed to data analysis and manuscript writing.

[^1]: Deceased

[^2]: Supporting information for this article is available on the Nature Medicine website ([doi:10.1038/s41543-019-0067-x](

[^3]: Manuscript received June 30, 2018; final manuscript received December 5, 2019.
The overall objectives of this application are to answer the questions: are maternal stresses during pregnancy detrimental to offspring, and does early postnatal stress have lasting effects on health outcomes in adulthood? To answer these questions, we use a novel experimental model in rats where maternal stress during pregnancy and lactation results in altered offspring behavior and gene expression in reward and stress-response circuits in adulthood. In addition, we use the natural variation of dam-rearing conditions in a rat colony at Washington State University as a model of maternal stress in rats to examine its effects on offspring physiology and behavior. Using this experimental model, we propose to test the following hypotheses: Specific Aim 1: Maternal stress during pregnancy and lactation has lasting effects on offspring hypothalamus-pituitary-adrenal (HPA) axis and brain gene expression that alter the brain-adrenal-tissue interaction during stress responses, and result in higher stress reactivity and higher pro-inflammatory cytokine levels. Specific Aim 2: Maternal stress during early postnatal (postnatal day 10, P10) stages of development alters the HPA axis,

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