Letters to Nature

Nature 394, 787-790 (20 August 1998) | doi:10.1038/29542; Received 24 March 1998; Accepted 18 June 1998

Stress and glucocorticoids impair retrieval of long-term spatial memory

Dominique J.-F. de Quervain1, Benno Roozendaal1 & James L. McGaugh1,2

  1. Center for the Neurobiology of Learning and Memory, University of California, Irvine, California 92697-3800, USA
  2. Department of Psychobiology, University of California, Irvine, California 92697-3800, USA

Correspondence to: Benno Roozendaal1 Correspondence and requests for materials should be addressed to B.R. (e-mail: Email: roozenda@darwin.bio.uci.edu).

Extensive evidence from animal and human studies indicates that stress and glucocorticoids influence cognitive function1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11. Previous studies have focused exclusively on glucocorticoid effects on acquisition and long-term storage of newly acquired information. Here we report that stress and glucocorticoids also affect memory retrieval. We show that rats have impaired performance in a water-maze spatial task after being given footshock 30 min before retention testing but are not impaired when footshock is given 2 min or 4 h before testing. These time-dependent effects on retention performance correspond to the circulating corticosterone levels at the time of testing, which suggests that the retention impairment is directly related to increased adrenocortical function. In support of this idea, we find that suppression of corticosterone synthesis with metyrapone blocks the stress-induced retention impairment. In addition, systemic corticosterone administered to non-stressed rats 30 min before retention testing induces dose-dependent retention impairment. The impairing effects of stress and glucocorticoids on retention are not due to disruption of spatial navigation per se. Our results indicate that besides the well described effects of stress and glucocorticoids on acquisition and consolidation processes, glucocorticoids also affect memory retrieval mechanisms.