生物谷报道：精神活性物质的滥用，如海洛因、可卡因、酒、烟草等，都可以导致成瘾。成瘾的主要特征是反复持续存在的心理渴求，即在药物的身体依赖戒断后，成瘾者对药物的心理依赖和药物愉快体验的记忆长期存在，甚至终生不能消退。通过研究药物成瘾记忆的神经生物学过程和其可能的干预措施是近年来神经科学的研究热点。
学习和记忆是人类获取外界信息、积累既往经验和维持正常生活的基本过程。对新信息的记忆需要巩固和再巩固后才能稳定下来，并在大脑的特定神经结构中长期保存。旧的记忆经过唤起后可以变得不稳定，需要再次巩固才能稳定和长期储存。根据记忆巩固和再巩固的理论，北京大学中国药物依赖性研究所近期研究发现，成瘾记忆也有明显的巩固和再巩固的过程，顽固的药物成瘾记忆被唤起后，经过适当的干预，成瘾记忆可以被抹去。近日出版的期刊《神经科学杂志》（Journal of Neuroscience）发表了这项最新的研究成果。
采用大鼠成瘾模型，经过几次吗啡训练后，大鼠就会对给药的环境产生明显的偏爱，即形成了稳定的药物记忆，如果不给干预，这种成瘾性记忆可以保持很长时间而不会消退。成瘾大鼠于戒断吗啡后再次会到原来的给药环境，其原来关于药物的记忆就可以被唤起。经过研究发现， 在大鼠成瘾记忆被唤起后，给于强烈的冰水应激，可以破坏成瘾记忆的再巩固，从而使原来的记忆消失。
进一步的研究发现，冰水应激诱导的成瘾记忆的消失是通过体内应激激素皮质酮介导的，因为给大鼠注射皮质酮同样能够损害药物记忆再巩固过程，且该损害持续很长时间而不能恢复。如果应激前给予皮质酮合成抑制剂美替拉酮，能够阻断应激对药物记忆再巩固的损害作用。 使用神经核团微注射技术，王晓艺等人还发现，应激诱导成瘾记忆的破坏主要是由基底外侧杏仁核糖皮质激素受体介导的。大脑结构中的杏仁核是控制情绪和应急反应的中枢，也是情感记忆和成瘾记忆的核心。
这一研究成果有重要的应用价值。吸毒病人出戒毒所后，虽然生理上恢复正常，暂时脱离毒品，但对过去吸毒时愉快记忆仍然强烈，在社会上很容易再次吸毒。如果有药物和一些医学措施使吸毒者忘记过去的愉快记忆，就有可能是吸毒者戒除毒品后不再为了追求愉快感而经常复发。（生物谷www.bioon.com）
生物谷推荐原始出处：
Journal of Neuroscience，May 21, 2008, 28(21):5602-5610，Xiao-Yi Wang, Lin Lu
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@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.
