Disrupting reconsolidation of drug memories reduces cocaine-seeking behavior.
Maladaptive memories that associate environmental stimuli with the effects of drugs of abuse are known to be a major cause of relapse to, and persistence of, a drug addictive habit. However, memories may be disrupted after their acquisition and consolidation by impairing their reconsolidation. Here, we show that infusion of Zif268 antisense oligodeoxynucleotides into the basolateral amygdala, prior to the reactivation of a well-learned memory for a conditioned stimulus (CS)-cocaine association, abolishes the acquired conditioned reinforcing properties of the drug-associated stimulus and thus its impact on the learning of a new cocaine-seeking response. Furthermore, we show that reconsolidation of CS-fear memories also requires Zif268 in the amygdala. These results demonstrate that appetitive CS-drug memories undergo reconsolidation in a manner similar to aversive memories and that this amygdala-dependent reconsolidation can be disrupted to reduce the impact of drug cues on drug seeking.
Lee
Jonathan L C
JL
Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, United Kingdom. jlcl2@cam.ac.uk
Di Ciano
Patricia
P
Thomas
Kerrie L
KL
Everitt
Barry J
BJ
D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003213:Conditioning, Psychological / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D005239:Fear; D008297:Male; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000139:chemically induced / Q000503:physiopathology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D012054:Reinforcement, Psychology; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D020319:Oligodeoxyribonucleotides, Antisense; D003042:Cocaine