Cue-induced alcohol-seeking behaviour is reduced by disrupting the reconsolidation of alcohol-related memories |
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Authors: | Christoph von der Goltz Valentina Vengeliene Ainhoa Bilbao Stephanie Perreau-Lenz Cornelius R. Pawlak Falk Kiefer Rainer Spanagel |
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Affiliation: | (1) Department of Addictive Behaviour and Addiction Medicine, University of Heidelberg, Central Institute of Mental Health (CIMH), J5, 68159 Mannheim, Germany;(2) Department of Psychopharmacology, University of Heidelberg, Central Institute of Mental Health (CIMH), J5, 68159 Mannheim, Germany |
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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. C. von der Goltz and V. Vengeliene contributed equally to this work. |
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Keywords: | Memory reconsolidation Alcohol addiction Relapse Anisomycin MK-801 Acamprosate Rat |
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