HIPPOCAMPAL MINERALOCORTICOID, BUT NOT GLUCOCORTICOID, RECEPTORS MODULATE ANXIETY-LIKE BEHAVIOR IN RATS

Stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis is regulated by negative-feedback mechanisms in the form of cytos olic and nuclear steroid receptors, sensitive to levels of circulating corticosterone (CORT), There are two types of steroid binding sites f ound in the brain: (i) mineralocorticoid receptors (MR); and (ii) gluc ocorticoid receptors (GR). The hippocampus expresses the highest densi ty of both MR and GR relative to other brain regions, and has long bee n recognized as a principal component controlling HPA axis inhibition. Because hippocampal cholinergic blockade produced anxiety-like behavi our, and affected HPA axis function, me explored if the induction of a nxiety might be attributable to changes in CORT. CORT also produced an xiety, although in a qualitatively unique manner than that produced by cholinergic blockade. In the present study, we have examined if CORT- induced anxiety occurs through an interaction with hippocampal MR or G R. Adult, male Lister Hooded rats were implanted bilaterally with hipp ocampal cannulae, and received infusions of either the MR antagonist, spironolactone (150 ng), or the GR antagonist, RU38486 (150 ng), eithe r 10 min or 3 h prior to being tested in the Black-White box. MR block ade, 10 min prior to testing, led to a pronounced anxiolytic effect as revealed by the increased amount of time spent in the white compartme nt, and increased amount of intercompartmental exploration, There was no effect of MR blockade 3 h prior to testing, and GR antagonism produ ced no effects at either pretreatment time. These data are the first t o show that hippocampal MR are directly involved in anxiety; moreover, the time course of the effect demonstrates that a non-genomic mechani sm probably underlies this response. Stress may be an important predis posing factor in the development and expression of anxiety. Copyright (C) 1997 Elsevier Science Inc.