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.
Department of Addictive Behaviour and Addiction Medicine, University of Heidelberg, Central Institute of Mental Health, J5, 68159 Mannheim, Germany.
Christoph
C
von der Goltz
Valentina
V
Vengeliene
Ainhoa
A
Bilbao
Stephanie
S
Perreau-Lenz
Cornelius R
CR
Pawlak
Falk
F
Kiefer
Rainer
R
Spanagel
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