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The NMDA receptor antagonist MK-801 fails to impair long-term recognition memory in mice when the state-dependency of memory is controlled.

Chan, M and Austen, J. M. and Eacott, M. J. and Easton, A. and Sanderson, D. J. (2019) 'The NMDA receptor antagonist MK-801 fails to impair long-term recognition memory in mice when the state-dependency of memory is controlled.', Neurobiology of learning and memory., 161 . pp. 57-62.


NMDA receptor-dependent synaptic plasticity has been proposed to be important for encoding of memories. Consistent with this hypothesis, the non-competitive NMDA receptor antagonist, MK-801, has been found to impair performance on tests of memory. Interpretation of some of these findings has, however, been complicated by the fact that the drug state of animals has differed during encoding and tests of memory. Therefore, it is possible that MK-801 may result in state-dependent retrieval or expression of memory rather than actually impairing encoding itself. We tested this hypothesis in mice using tests of object recognition memory with a 24-hour delay between the encoding and test phase. Mice received injections of either vehicle or MK-801 prior to the encoding phase and the test phase. In Experiment 1, a low dose of MK-801 (0.01mg/kg) impaired performance when the drug state (vehicle or MK-801) of mice changed between encoding and test, but there was no significant effect of MK-801 on encoding. In Experiment 2, a higher dose of MK-801 (0.1mg/kg) failed to impair object recognition memory when mice received the drug prior to both encoding and test compared to mice that received vehicle. MK-801 did not affect object exploration, but it did induce locomotor hyperactivity at the higher dose. These results suggest that some previous demonstrations of MK-801 effects may reflect a failure to express or retrieve memory due to the state-dependency of memory rather than impaired encoding of memory.

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Publisher statement:© 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (
Date accepted:18 March 2019
Date deposited:22 March 2019
Date of first online publication:19 March 2019
Date first made open access:22 March 2019

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