Stress-related modulation of hippocampal long-term potentiation in rats: Involvement of adrenal steroid receptors

Stress is usually correlated with an increased release of glucocorticoids from the adrenal glands. Within the hippocampus, a structure long known to be involved in spatial learning, two corticosterone-binding receptors are identified: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Activation of these receptors impairs or facilitates hippocampal long-term potentiation (LTP), respectively. Stress elicited by behavioral manipulations may interfere with cognitive modulations of LTP during learning experiments. Here, we explore the influence of two stress-inducing procedures, handling and swimming, on the maintenance of dentate gyrus LTP in the rat induced by a weak tetanization of the perforant path. Manipulations started 15 min after tetanization. Handling alone resulted in a complete reversal of LTP. Handling followed by a 2 min swim in a water tank elicited prolonged protein synthesis but not β-adrenergic-dependent LTP compared with either control or handled animals. Blockade of the GRs but not of the MRs prevented the reversal of LTP by handling. Inactivation of the MRs but not of the GRs hindered LTP prolongation by swimming. Because the activated receptor complexes act as transcription factors, MR- and GR-related proteins may play a role in the maintenance of LTP. The data suggest a complex interplay of corticosterone-binding receptors on modulations of hippocampal LTP and thus, of stress on learning and functional plasticity in general.