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


OBJECTIVE
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.
von der Goltz
Christoph
C
Department of Addictive Behaviour and Addiction Medicine, University of Heidelberg, Central Institute of Mental Health, J5, 68159 Mannheim, Germany.
Vengeliene
Valentina
V
Bilbao
Ainhoa
A
Perreau-Lenz
Stephanie
S
Pawlak
Cornelius R
CR
Kiefer
Falk
F
Spanagel
Rainer
R
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000494:pharmacology; D019973:Alcohol-Related Disorders / Q000523:psychology; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D016739:Behavior, Addictive / Q000503:physiopathology / Q000517:prevention & control*; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D016291:Dizocilpine Maleate / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D008568:Memory / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012646:Self Administration; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology
D000427:Alcohol Deterrents; D011500:Protein Synthesis Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D013654:Taurine; D000431:Ethanol; D000841:Anisomycin; D016291:Dizocilpine Maleate; D000077443:Acamprosate