The effect of social stress on hippocampal gene expression.

The housing of male and female rats in a visible burrow system in which a dominance hierarchy is established and interactions between animals can be monitored provides an effective method by which the behavioral and neuroendocrine effects of social stress can be examined. In this social system, subordinate male rats exhibit plasma corticosterone levels that appear to be chronically elevated relative to the dominant rats in the colonies and compared to singly housed controls. Previous studies have indicated that in the hippocampus adrenal steroids negatively regulate the expression of the mRNAs encoding the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and the growth-associated protein GAP-43, while the preproenkephalin (ppENK) mRNA is positively regulated by glucocorticoids. This study examined the effect of social stress and the resulting sustained increase in steroid levels in the subordinate animals on gene expression in the hippocampus. The results indicated that GR, MR, and GAP-43 mRNAs were decreased in subordinate rats relative to controls, in the CA1 region of the hippocampus, while ppENK mRNA was unaffected. No statistically significant differences in mRNA expression were observed in other hippocampal subfields. These findings suggest that the social stress encountered by the subordinate rats in this burrow environment elicits changes in hippocampal gene expression that are consistent with their regulation by adrenal steroids.