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Cue-induced alcohol-seeking behaviour is reduced by disrupting the reconsolidation of alcohol-related memories

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Abstract

Rationale

In humans, the retrieval of memories associated with an alcohol-related experience frequently evokes alcohol-seeking behaviour. The reconsolidation hypothesis states that a consolidated memory could again become labile and susceptible to disruption after memory retrieval.

Objectives

The aim of our study was to examine whether retrieval of alcohol-related memories undergoes a reconsolidation process.

Methods

For this purpose, male Wistar rats were trained to self-administer ethanol in the presence of specific conditioned stimuli. Thereafter, animals were left undisturbed in their home cages for the following 21 days. Memory retrieval was performed in a single 5-min exposure to all alcohol-associated stimuli. The protein synthesis inhibitor anisomycin, the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 and acamprosate, a clinically used drug known to reduce a hyper-glutamatergic state, were given immediately after retrieval of alcohol-related memories. The impact of drug treatment on cue-induced alcohol-seeking behaviour was measured on the following day and 7 days later.

Results

Administration of both anisomycin and MK-801 reduced cue-induced alcohol-seeking behaviour, showing that memory reconsolidation was disrupted by these compounds. However, acamprosate had no effect on the reconsolidation process, suggesting that this process is not dependent on a hyper-glutamatergic state but is more related to protein synthesis and NMDA receptor activity.

Conclusions

Pharmacological disruption of reconsolidation of alcohol-associated memories can be achieved by the use of NMDA antagonists and protein synthesis inhibitors and may thus provide a potential new therapeutic strategy for the prevention of relapse in alcohol addiction.

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Acknowledgements

We thank Sabrina Koch and Elisabeth Röbel for excellent technical assistance. This work was supported by two SFB636 grants—B1 given to RS and D6 given to FK.

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Authors and Affiliations

  1. Department of Addictive Behaviour and Addiction Medicine, University of Heidelberg, Central Institute of Mental Health (CIMH), J5, 68159, Mannheim, Germany

    Christoph von der Goltz & Falk Kiefer

  2. Department of Psychopharmacology, University of Heidelberg, Central Institute of Mental Health (CIMH), J5, 68159, Mannheim, Germany

    Valentina Vengeliene, Ainhoa Bilbao, Stephanie Perreau-Lenz, Cornelius R. Pawlak & Rainer Spanagel

Authors
  1. Christoph von der Goltz
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  2. Valentina Vengeliene
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  3. Ainhoa Bilbao
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  4. Stephanie Perreau-Lenz
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  5. Cornelius R. Pawlak
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  6. Falk Kiefer
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  7. Rainer Spanagel
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Corresponding author

Correspondence to Valentina Vengeliene.

Additional information

C. von der Goltz and V. Vengeliene contributed equally to this work.

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von der Goltz, C., Vengeliene, V., Bilbao, A. et al. Cue-induced alcohol-seeking behaviour is reduced by disrupting the reconsolidation of alcohol-related memories. Psychopharmacology 205, 389–397 (2009). https://doi.org/10.1007/s00213-009-1544-1

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  • DOI: https://doi.org/10.1007/s00213-009-1544-1

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