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Stress and glucocorticoids impair retrieval of long-term spatial memory


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.

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Figure 1: Effects of pre-testing exposure to footshock on retention performance.
Figure 2: Effects of pre-testing manipulation of glucocorticoid levels on retention performance.


  1. Conrad, C. D., Galea, L. A. M., Kuroda, Y. & McEwen, B. S. Chronic stress impairs spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment. Behav. Neurosci. 110, 1321–1334 (1996).

    Article  CAS  Google Scholar 

  2. Kirschbaum, C., Wolf, O. T., May, M., Wippich, W. & Hellhammer, D. H. Stress- and treatment-induced elevations of cortisol levels associated with impaired declarative memory in healthy adults. Life Sci. 58, 1475–1483 (1996).

    Article  CAS  Google Scholar 

  3. Luine, V. N., Spencer, R. L. & McEwen, B. S. Effects of chronic corticosterone ingestion on spatial memory performance and hippocampal serotonergic function. Brain Res. 616, 65–70 (1993).

    Article  CAS  Google Scholar 

  4. Luine, V., Villegas, M., Martinez, C. & McEwen, B. S. Repeated stress causes reversible impairments of spatial memory performance. Brain Res. 639, 167–170 (1994).

    Article  CAS  Google Scholar 

  5. Luine, V., Martinez, C., Villegas, M., Magarinos, A. M. & McEwen, B. S. Restraint stress reversibly enhances spatial memory performance. Physiol. Behav. 59, 27–32 (1996).

    Article  CAS  Google Scholar 

  6. Lupien, S. J. & McEwen, B. S. The acute effects of corticosteroids on cognition: integration of animal and human model studies. Brain Res. Rev. 24, 1–27 (1997).

    Article  CAS  Google Scholar 

  7. Lupien, S. al. Stress-induced declarative memory impairment in healthy elderly subjects: relationship to cortisol reactivity. J. Clin. Endocrinol. Metabol. 82, 2070–2075 (1997).

    CAS  Google Scholar 

  8. Newcomer, J. W., Craft, S., Hershey, T., Askins, K. & Bardgett, M. E. Glucocorticoid-induced impairment in declarative memory performance in adult humans. J. Neurosci. 14, 2047–2053 (1994).

    Article  CAS  Google Scholar 

  9. Roozendaal, B. & McGaugh, J. L. Amygdaloid nuclei lesions differentially affect glucocorticoid-induced memory enhancement in an inhibitory avoidance task. Neurobiol. Learn. Memory 65, 1–8 (1996).

    Article  CAS  Google Scholar 

  10. Sandi, C., Loscertales, M. & Guaza, C. Experience-dependent facilitating effect of corticosterone on spatial memory formation in the water maze. Eur. J. Neurosci. 9, 637–642 (1997).

    Article  CAS  Google Scholar 

  11. Shors, T. J., Weiss, C. & Thompson, R. F. Stress-induced facilitation of classical conditioning. Science 257, 537–539 (1992).

    Article  ADS  CAS  Google Scholar 

  12. Morris, R. Developments of a water-maze procedure for studying spatial learning in the rat. J. Neurosci. Meth. 11, 47–60 (1984).

    Article  CAS  Google Scholar 

  13. De Boer, S. F., Koopmans, S. J., Slangen, J. L. & Van der Gugten, J. Plasma catecholamine, corticosterone and glucose responses to repeated stress in rats: Effects of interstressor interval length. Physiol. Behav. 47, 1117–1124 (1990).

    Article  CAS  Google Scholar 

  14. Roozendaal, B., Bohus, B. & McGaugh, J. L. Dose-dependent suppression of adrenocortical activity with metyrapone: Effects on emotion and memory. Psychoneuroendocrinol. 21, 681–693 (1996).

    Article  CAS  Google Scholar 

  15. Oitzl, M. S. & De Kloet, E. R. Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. Behav. Neurosci. 106, 62–71 (1992).

    Article  CAS  Google Scholar 

  16. McEwen, B. S. Glucocorticoid-biogenic amine interactions in relation to mood and behavior. Horm. Behav. 28, 396–405 (1994).

    Article  CAS  Google Scholar 

  17. De Kloet, E. R. Brain corticosteroid receptor balance and homeostatic control. Front. Neuroendocrinol. 12, 955–164 (1991).

    Google Scholar 

  18. Joëls, M., Karst, H., Hesen, W. & Wadman, W. J. in Brain Corticosteroid Receptors(eds De Kloet, E. R., Azmitia, E. C. & Landfield, P. W.) 166–177 (Ann. NY Acad. Sci. 746, (1994)).

    Google Scholar 

  19. Thomas, D. N., Post, R. M. & Pert, A. in Brain Corticosteroid Receptors(eds De Kloet, E. R., Azmitia, E. C. & Landfield, P. W.) 467–469 (Ann. NY Acad. Sci. 746, (1994)).

    Google Scholar 

  20. Orchinik, M., Moore, F. L. & Rose, J. D. in Brain Corticosteroid Receptors(eds De Kloet, E. R., Azmitia, E. C. & Landfield, P. W.) 101–114 (Ann. NY Acad. Sci. 746, (1994)).

    Google Scholar 

  21. Monk, T. al. Circadian rhythms in human performance and mood under constant conditions. J. Sleep Res. 6, 9–18 (1997).

    Article  CAS  Google Scholar 

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We thank R. M. Sapolsky and S. Brooke for performing the corticosterone assay, and B. Bohus for his comments on an early draft of this paper. The research was supported by a grant from NIMH.

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Correspondence to Benno Roozendaal.

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de Quervain, DF., Roozendaal, B. & McGaugh, J. Stress and glucocorticoids impair retrieval of long-term spatial memory. Nature 394, 787–790 (1998).

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