The basolateral amygdala and nucleus accumbens core mediate dissociable aspects of drug memory reconsolidation.
A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug craving and relapse. Exposure to drug-paired cues not only precipitates relapse, but also triggers the reactivation and reconsolidation of the cue-drug memory. However, the limbic cortical-striatal circuitry underlying drug memory reconsolidation is unclear. The aim of this study was to investigate the involvement of the nucleus accumbens core and the basolateral amygdala in the reconsolidation of a cocaine-conditioned stimulus-evoked memory. Antisense oligodeoxynucleotides (ASO) were infused into each structure to knock down the expression of the immediate-early gene zif268, which is known to be required for memory reconsolidation. Control infusions used missense oligodeoxynucleotides (MSO). The effects of zif268 knockdown were measured in two complementary paradigms widely used to assess the impact of drug-paired CSs upon drug seeking: the acquisition of a new instrumental response with conditioned reinforcement and conditioned place preference. The results show that both intranucleus accumbens core and intrabasolateral amygdala zif268 ASO infusions at memory reactivation impaired the reconsolidation of the memory underlying a cocaine-conditioned place preference. However, knockdown of zif268 in the nucleus accumbens at memory reactivation had no effect on the memory underlying the conditioned reinforcing properties of the cocaine-paired CS measured subsequently, and this is in contrast to the marked impairment observed previously following intrabasolateral amygdala zif268 ASO infusions. These results suggest that both the basolateral amygdala and nucleus accumbens core are key structures within limbic cortical-striatal circuitry where reconsolidation of a cue-drug memory occurs. However reconsolidation of memory representations formed during Pavlovian conditioning are differentially localized in each site.
Théberge
Florence R M
FR
Department of Experimental Psychology, University of Cambridge, Cambridge, United Kingdom.
Milton
Amy L
AL
Belin
David
D
Lee
Jonathan L C
JL
Everitt
Barry J
BJ
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology*; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D009434:Neural Pathways / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology*
D000697:Central Nervous System Stimulants; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D020319:Oligodeoxyribonucleotides, Antisense; D003042:Cocaine
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