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Male Sprague\u2013Dawley rats were restrained for 6\u2003h\/day\/21\u2003days, and spatial memory was assessed on the Y\u2010maze on day\u200322. Ninety minutes before training, rats received a subcutaneous injection of vehicle or metyrapone, a CORT synthesis inhibitor, and then spatial memory was determined 4\u2010h later. The highest dose of metyrapone (75\u2003mg\/kg, s.c.) was most effective at preventing stress\u2010induced spatial memory deficits. Chronic stress increased total CORT levels following Y\u2010maze exposure, while acute metyrapone treatment dose\u2010dependently attenuated total and free (unbound) CORT levels in both stress and control conditions. Blood samples taken from a separate subset of chronically stressed rats showed that baseline CORT levels were similar across the restraint period. Finally, chronic stress down\u2010regulated glucocorticoid, but not mineralocorticoid, receptor mRNA expression within the hippocampus (dentate gyrus, CA1, CA2, CA3). These findings suggest that chronic stress\u2010induced spatial memory deficits may be mediated by hypothalamic\u2010pituitary\u2010adrenal axis dysregulation. Specifically, CORT elevations and reductions in hippocampal glucocorticoid receptor expression, at the time of behavioural assessment may be involved, as opposed to a direct effect that is solely dependent upon hippocampal structural changes. These results have significance for treating cognitive decline in conditions associated with elevated glucocorticoids that include subpopulations in ageing, depression, Cushing's disease and Alzheimer's disease.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2006.04948.x","type":"journal-article","created":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T16:15:29Z","timestamp":1153239329000},"page":"595-605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Attenuating corticosterone levels on the day of memory assessment prevents chronic stress\u2010induced impairments in spatial memory"],"prefix":"10.1111","volume":"24","author":[{"given":"Ryan L.","family":"Wright","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth N.","family":"Lightner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James 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