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Midazolam does not inhibit association formation, just its storage and strengthening

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Abstract

Rationale

Although there have been many studies examining the effects of benzodiazepines on memory performance, their effects on working memory are equivocal and little is known about whether they affect the efficacy of practice of already learned material.

Objectives

The objectives in two experiments were to examine (a) whether midazolam impairs performance on a working memory task designed to minimize mnemonic strategies such as rehearsal or chunking of information to be recalled and (b) the effect of midazolam on repeated practice of paired associates that were learned before drug administration.

Materials and methods

Both experiments involved subcutaneous administration of 0.03 mg of saline or midazolam per kilogram of bodyweight in within-subject, placebo-controlled designs, involving 23 subjects in (a) and 31 in (b).

Results

The drug had no effect on the ability to recall the digits in serial order even though the encoding task prevented the digits from being rehearsed or maintained in an articulatory buffer. Paired associates that were learned before the injection showed a benefit of subsequent practice under saline but not under midazolam.

Conclusions

The results suggest that (a) midazolam does not affect the formation of new associations in short-term memory provided that the presentation rate is not too fast to form these associations when sedated, despite the evidence that the drug blocks long-term memory (LTM) retention of associations; and (b) the potential for over-learning with practice of learned associations in LTM is adversely affected by midazolam such that repeated exposures do not strengthen new learning.

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Notes

  1. The weight cutoff was a conservative value approved by the IDS of the University of Pittsburgh), We could have used a more liberal (higher weight) cutoff without compromising safety.

  2. We examined the episodic memory effects at 17 min in a different study (Reder et al. 2006). Paired associates that were studied for the first time were recalled correctly 33% of the time in the saline condition but only 9% of the time in the midazolam condition. It should be noted, however, that it is possible that the same drug has different windows for its effects on various cognitive functions (e.g., a longer window of action for its effects on episodic memory than for its effects on working memory).

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Acknowledgements

This work was supported by grants 2-R01-MH52808 and R01-MH068243 from the National Institute of Mental Health. We thank Daniel Dickison for consultations and help with the analyses and programs. We also thank Michael Dulik, Jennifer Ferris, Brandi Jefferson, Abigail Kaufer, Jennifer Sauer, Edward Thornton, and Esther Vespa for help in running the test/trials and in monitoring the subjects.

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Authors and Affiliations

  1. Psychology Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA

    Lynne M. Reder, Iain Proctor, John R. Anderson & Joyce M. Oates

  2. Department of Anesthesia, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Ferenc Gyulai & Joseph J. Quinlan

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  1. Lynne M. Reder
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  2. Iain Proctor
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  3. John R. Anderson
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  4. Ferenc Gyulai
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  6. Joyce M. Oates
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Correspondence to Lynne M. Reder.

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Reder, L.M., Proctor, I., Anderson, J.R. et al. Midazolam does not inhibit association formation, just its storage and strengthening. Psychopharmacology 188, 462–471 (2006). https://doi.org/10.1007/s00213-006-0436-x

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  • DOI: https://doi.org/10.1007/s00213-006-0436-x

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