Long-term effects of Preweaning environmental impoverishment on neurobehavioral and neurocognitive outcomes in Sprague Dawley rats: An early environmental stress model

Abstract

Developmental stress, including low socioeconomic status (SES), can induce dysregulation of the hypothalamic-pituitary-adrenal axis and result in long-term changes in stress reactivity. Children in lower SES conditions often experience more stress than those in other SES groups. There are multiple model systems of early environmental stress (EES), one of which is reduced cage bedding. Here we tested the effects of both prenatal and lactational EES in rats on a range of long-term behavioral and cognitive outcomes. There were persistent reductions in body weight in the EES rats in both sexes. The behavioral results showed no effects on learning and memory using tests of spatial learning or cognitive flexibility in the Morris water maze, egocentric learning in the Cincinnati water maze, or working memory in the radial-arm maze. There were no effects on basic open-field activity, elevated zero-maze, or forced swim test, but EES rats had reduced time in the dark side of the light/dark test. When rats were drug challenged in the open-field with d-amphetamine or MK-801, there were no differential responses to d-amphetamine, but the EES group under responded compared with the drug-induced hyperactivity in the control group in both males and females. The objective was to establish a developmental stress model that induced cognitive deficits and to the extent that this method did not cause such effects it was not the model we sought. However, the data showed several long-term effects of EES, including the reduced response to the irreversible NMDA antagonist MK-801. This effect merits further investigation.