生物谷報道：精神活性物質的濫用，如海洛因,、可卡因,、酒、煙草等,，都可以導致成癮,。成癮的主要特征是反復持續(xù)存在的心理渴求，即在藥物的身體依賴戒斷后,，成癮者對藥物的心理依賴和藥物愉快體驗的記憶長期存在,，甚至終生不能消退。通過研究藥物成癮記憶的神經生物學過程和其可能的干預措施是近年來神經科學的研究熱點,。
學習和記憶是人類獲取外界信息,、積累既往經驗和維持正常生活的基本過程。對新信息的記憶需要鞏固和再鞏固后才能穩(wěn)定下來,，并在大腦的特定神經結構中長期保存,。舊的記憶經過喚起后可以變得不穩(wěn)定，需要再次鞏固才能穩(wěn)定和長期儲存,。根據記憶鞏固和再鞏固的理論,，北京大學中國藥物依賴性研究所近期研究發(fā)現(xiàn)，成癮記憶也有明顯的鞏固和再鞏固的過程,，頑固的藥物成癮記憶被喚起后,，經過適當的干預，成癮記憶可以被抹去,。近日出版的期刊《神經科學雜志》（Journal of Neuroscience）發(fā)表了這項最新的研究成果,。
采用大鼠成癮模型，經過幾次嗎啡訓練后,，大鼠就會對給藥的環(huán)境產生明顯的偏愛,，即形成了穩(wěn)定的藥物記憶，如果不給干預,，這種成癮性記憶可以保持很長時間而不會消退,。成癮大鼠于戒斷嗎啡后再次會到原來的給藥環(huán)境,，其原來關于藥物的記憶就可以被喚起。經過研究發(fā)現(xiàn),， 在大鼠成癮記憶被喚起后,，給于強烈的冰水應激，可以破壞成癮記憶的再鞏固,，從而使原來的記憶消失,。
進一步的研究發(fā)現(xiàn)，冰水應激誘導的成癮記憶的消失是通過體內應激激素皮質酮介導的,，因為給大鼠注射皮質酮同樣能夠損害藥物記憶再鞏固過程，且該損害持續(xù)很長時間而不能恢復,。如果應激前給予皮質酮合成抑制劑美替拉酮,，能夠阻斷應激對藥物記憶再鞏固的損害作用。 使用神經核團微注射技術,，王曉藝等人還發(fā)現(xiàn),，應激誘導成癮記憶的破壞主要是由基底外側杏仁核糖皮質激素受體介導的。大腦結構中的杏仁核是控制情緒和應急反應的中樞,，也是情感記憶和成癮記憶的核心,。
這一研究成果有重要的應用價值。吸毒病人出戒毒所后,，雖然生理上恢復正常,，暫時脫離毒品，但對過去吸毒時愉快記憶仍然強烈,，在社會上很容易再次吸毒,。如果有藥物和一些醫(yī)學措施使吸毒者忘記過去的愉快記憶，就有可能是吸毒者戒除毒品后不再為了追求愉快感而經常復發(fā),。（生物谷www.bioon.com）
生物谷推薦原始出處：
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: [email protected]
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.
