Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response.

Abstract

The hippocampus is the principal target site in the brain for adrenocortical steroids, as it has the highest concentration of receptor sites for glucocorticoids. The aged rat has a specific deficit in hippocampal glucocorticoid receptors, owing in large part to a loss of corticoid-sensitive neurons. This deficit may be the cause for the failure of aged rats to terminate corticosterone secretion at the end of stress, because extensive lesion and electrical stimulation studies have shown that the hippocampus exerts an inhibitory influence over adrenocortical activity and participates in glucocorticoid feedback. Whether it is the loss of hippocampal neurons or of hippocampal glucocorticoid receptors in the aged rat that contributes most to this syndrome of corticosterone hypersecretion was investigated. Two model systems for producing reversible glucocorticoid receptor depletion in the hippocampus were used. Depletion of receptors without inducing cell loss results in corticosterone hypersecretion. Correction of the receptor deficit results in normalization of corticosterone secretion. The hippocampus as an important glucocorticoid sensor in relation to the stress response was emphasized. New physiological correlates for the remarkable plasticity of the hippocampal glucocorticoid receptor system, which is under independent control by corticosterone and by vasopressin are provided.