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The Journal of Neuroscience, May 21, 2008, 28(21):5602-5610; doi:10.1523/JNEUROSCI.0750-08.2008

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Behavioral/Systems/Cognitive
Stress Impairs Reconsolidation of Drug Memory via Glucocorticoid Receptors in the Basolateral Amygdala

Xiao-Yi Wang,¹ Mei Zhao,¹ Udi E. Ghitza,² Yan-Qin Li,¹ and Lin Lu¹

¹Department of Neuropharmacology, National Institute on Drug Dependence, Peking University, Beijing 100083, China, and ²Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224

Correspondence should be addressed to Dr. Lin Lu, National Institute on Drug Dependence, Peking University, 38, Xue Yuan Road, Haidian District, Beijing 100083, China. Email: linlu{at}bjmu.edu.cn

Relapse to drug taking induced by exposure to cues associated with drugs of abuse is a major challenge to the treatment of drug addiction. Previous studies indicate that drug seeking can be inhibited by disrupting the reconsolidation of a drug-related memory. Stress plays an important role in modulating different stages of memory including reconsolidation, but its role in the reconsolidation of a drug-related memory has not been investigated. Here, we examined the effects of stress and corticosterone on reconsolidation of a drug-related memory using a conditioned place preference (CPP) procedure. We also determined the role of glucocorticoid receptors (GRs) in the basolateral amygdala (BLA) in modulating the effects of stress on reconsolidation of this memory. We found that rats acquired morphine CPP after conditioning, and that this CPP was inhibited by stress given immediately after re-exposure to a previously morphine-paired chamber (a reconsolidation procedure). The disruptive effect of stress on reconsolidation of morphine related memory was prevented by inhibition of corticosterone synthesis with metyrapone or BLA, but not central amygdala (CeA), injections of the glucocorticoid (GR) antagonist RU38486 [(11,17)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one]. Finally, the effect of stress on drug related memory reconsolidation was mimicked by systemic injections of corticosterone or injections of RU28362 [11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one] (a GR agonist) into BLA, but not the CeA. These results show that stress blocks reconsolidation of a drug-related memory, and this effect is mediated by activation of GRs in the BLA.

Key words: memory; stress; morphine; corticosterone; reconsolidation; amygdala

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Received Feb. 18, 2008; revised April 1, 2008; accepted April 23, 2008.

Correspondence should be addressed to Dr. Lin Lu, National Institute on Drug Dependence, Peking University, 38, Xue Yuan Road, Haidian District, Beijing 100083, China. Email: linlu{at}bjmu.edu.cn

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