Disrupting Reconsolidation of Conditioned Withdrawal Memories in the Basolateral Amygdala Reduces Suppression of Heroin Seeking in Rats

Recent data from our laboratory have demonstrated that appetitive drug memories undergo protein synthesis-dependent reconsolidation in the basolateral amygdala (BLA), an area important in the formation of emotional memories. We here investigated the importance of the BLA in the reconsolidation of op...

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Bibliographic Details
Published in:The Journal of neuroscience 2006-12, Vol.26 (49), p.12694-12699
Main Authors: Hellemans, Kim G. C, Everitt, Barry J, Lee, Jonathan L. C
Format: Article
Language:English
Subjects:
Amygdala - metabolism
Animals
Behavior, Addictive - metabolism
Behavior, Addictive - psychology
Brief Communications
Conditioning, Psychological - physiology
Early Growth Response Protein 1 - biosynthesis
Heroin - administration & dosage
Heroin Dependence - metabolism
Heroin Dependence - psychology
Male
Memory - physiology
Rats
Substance Withdrawal Syndrome - metabolism
Substance Withdrawal Syndrome - psychology
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Summary:Recent data from our laboratory have demonstrated that appetitive drug memories undergo protein synthesis-dependent reconsolidation in the basolateral amygdala (BLA), an area important in the formation of emotional memories. We here investigated the importance of the BLA in the reconsolidation of opiate conditioned withdrawal memories. Rats with bilateral cannulas implanted in the BLA were trained to respond for heroin (0.12 mg/kg, i.v.) under a seeking-taking schedule, which required responding on a seeking lever to gain the opportunity to self-administer heroin by a single response on a taking lever. After induction of opiate dependence with subcutaneously implanted, heroin-filled osmotic minipumps (3 mg x kg(-1) x d(-1) heroin), rats received five consecutive pairings of a conditioned stimulus (CS) (tone, light, and odor compound) paired with naloxone (0.10 mg/kg, s.c.)-precipitated withdrawal. We replicated our previous findings that heroin seeking is suppressed in the presence of the withdrawal-associated CS. However, infusion of Zif268 antisense oligodeoxynucleotide into the BLA before reactivation of the CS-withdrawal association abolished this conditioned suppression in a reactivation-dependent manner. We also report that reconsolidation of CS-withdrawal memories upregulates Zif268 protein in the basolateral but not central nucleus of the amygdala and that Zif268 knockdown occurs selectively in the BLA. These results demonstrate that drug withdrawal memories undergo protein synthesis-dependent reconsolidation in the BLA and suggest a common mechanism for the reconsolidation of both appetitive and aversive drug memories.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.3101-06.2006