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Impairment of specific episodic memory processes by sub-psychotic doses of ketamine: the effects of levels of processing at encoding and of the subsequent retrieval task

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Abstract

Rationale

The precise nature of the impact of the N-methyl-d-aspartate antagonist, ketamine, upon human episodic memory, has yet to be elucidated fully.

Objectives

This study sought to assess the effects of ketamine on the sub-processes facilitating memory encoding and retrieval.

Methods

We evaluated the effects of the drug on a series of memory performance measures depending upon whether it was administered at the encoding or retrieval stage and on the nature of the encoding task used. Twelve healthy volunteers participated in a double-blind, placebo-controlled, randomized, within-subjects study. Intravenous infusions of placebo, 50 ng/ml ketamine or 100 ng/ml ketamine were administered. We investigated the effects of ketamine on three key aspects of episodic memory: encoding vs retrieval processes, source memory, and depth of processing. Data were analysed using both multinomial modelling and standard measures of item discrimination and response bias.

Results

Deleterious effects of ketamine on episodic memory were primarily attributable to its effects on encoding, rather than retrieval processes. Recognition memory was impaired for items encoded at an intermediate level of processing, but preserved for shallowly and deeply encoded items. Increased source guessing bias was also observed when encoding took place under ketamine.

Conclusions

The effects of ketamine upon episodic memory seem, therefore, to predominate at encoding. Furthermore, our results are also consistent with a specific impairment of encoding processes that result in subsequent recollective, as opposed to familiarity-based, retrieval. The observed effects are compatible with memory deficits seen in schizophrenia and thus provide some support for the ketamine model of the disease.

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Acknowledgements

This work was sponsored by a Wellcome Trust grant awarded to P.C.F. G.D.H. and R.A.E.H. were also supported by the Wellcome Trust; J.S.S. was supported by Wellcome Trust grant 061171. We would like to thank Trevor Robbins, Barbara Sahakian and Peter McKenna for their helpful contributions, the staff of the Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital for clinical support, and also the participants involved in the study.

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Authors and Affiliations

  1. Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, P.O. Box 255, Hills Road , Cambridge, CB2 2QQ, UK

    Garry D. Honey, Rebekah A. E. Honey, Danielle C. Turner, Edith Pomarol-Clotet, Dharshan Kumaran, Edward T. Bullmore & Paul C. Fletcher

  2. Department of Anesthesiology, University of Washington/Harborview Medical Center, Seattle, WA, 98104, USA

    Sam R. Sharar

  3. University College London, London, WC1N 3AR, UK

    Jon S. Simons

  4. Department of Psychology, University of Memphis, Memphis, TN, 38152-6400, USA

    Xiangen Hu

  5. Center for Neurobiology of Learning and Memory, University of California at Irvine, Irvine, CA, 92697-3800, USA

    Michael D. Rugg

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  1. Garry D. Honey
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  11. Paul C. Fletcher
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Correspondence to Paul C. Fletcher.

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Honey, G.D., Honey, R.A.E., Sharar, S.R. et al. Impairment of specific episodic memory processes by sub-psychotic doses of ketamine: the effects of levels of processing at encoding and of the subsequent retrieval task. Psychopharmacology 181, 445–457 (2005). https://doi.org/10.1007/s00213-005-0001-z

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  • DOI: https://doi.org/10.1007/s00213-005-0001-z

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