Viral vector-mediated blockade of the endocrine stress-response modulates non-spatial memory.

Stress results in the release of glucocorticoids (GCs) which at high levels, impair performance on hippocampus-dependent tasks. Estrogen is neurotrophic and can rescue stress-induced memory impairments. Here we report the use of a viral vector to overexpress a chimeric gene (ER/GR) that converts the deleterious effects of glucocorticoids into beneficial estrogenic effects. A short immobilization stress regimen was sufficient to impair non-spatial memory. In contrast, viral vector-mediated overexpression of ER/GR in the dentate gyrus of the hippocampus protected against stress-induced impairments of non-spatial memory. These data add to the growing evidence that increasing estrogenic signaling can protect against the impairing effects of stress on non-spatial memory.