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The Journal of Neuroscience, May 31, 2006, 26(22):5881-5887; doi:10.1523/JNEUROSCI.0323-06.2006

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Behavioral/Systems/Cognitive
Cue-Induced Cocaine Seeking and Relapse Are Reduced by Disruption of Drug Memory Reconsolidation

Jonathan L. C. Lee, Amy L. Milton, and Barry J. Everitt

Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom

Correspondence should be addressed to Jonathan L. C. Lee, Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. Email: jlcl2{at}cam.ac.uk

Long-lasting vulnerability to drug cue-induced relapse to a drug-taking habit is a major challenge to the treatment of drug addiction. Here we show that blockade of drug memory reconsolidation, through infusion of Zif268 antisense oligodeoxynucleotides into the basolateral amygdala shortly before reexposure to a cocaine-associated stimulus but not simply to the training context, severely impaired subsequently cue-maintained cocaine seeking under a second-order schedule of reinforcement and abolished cue-induced reinstatement of and relapse to cocaine seeking. This reduction in relapse after disrupted memory reconsolidation was not only seen after several hundred pairings of the stimulus with self-administered cocaine, but older, as well as recent, memories were also disrupted. Reconsolidation blockade may thus provide a potential therapeutic strategy for the prevention of relapse in drug addiction.

Key words: addiction; relapse; memory reconsolidation; basolateral amygdala; antisense oligodeoxynucleotides; rat

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Received Sept. 29, 2005; revised April 21, 2006; accepted April 22, 2006.

Correspondence should be addressed to Jonathan L. C. Lee, Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. Email: jlcl2{at}cam.ac.uk

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