生物谷報(bào)道：精神活性物質(zhì)的濫用,，如海洛因、可卡因,、酒,、煙草等，都可以導(dǎo)致成癮,。成癮的主要特征是反復(fù)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(duì)藥物的心理依賴和藥物愉快體驗(yàn)的記憶長(zhǎng)期存在，甚至終生不能消退,。通過研究藥物成癮記憶的神經(jīng)生物學(xué)過程和其可能的干預(yù)措施是近年來神經(jīng)科學(xué)的研究熱點(diǎn),。
學(xué)習(xí)和記憶是人類獲取外界信息、積累既往經(jīng)驗(yàn)和維持正常生活的基本過程,。對(duì)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(jīng)結(jié)構(gòu)中長(zhǎng)期保存。舊的記憶經(jīng)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(zhǎng)期儲(chǔ)存,。根據(jù)記憶鞏固和再鞏固的理論，北京大學(xué)中國(guó)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(jīng)過適當(dāng)?shù)母深A(yù),，成癮記憶可以被抹去。近日出版的期刊《神經(jīng)科學(xué)雜志》（Journal of Neuroscience）發(fā)表了這項(xiàng)最新的研究成果,。
采用大鼠成癮模型,，經(jīng)過幾次嗎啡訓(xùn)練后，大鼠就會(huì)對(duì)給藥的環(huán)境產(chǎn)生明顯的偏愛,，即形成了穩(wěn)定的藥物記憶,，如果不給干預(yù)，這種成癮性記憶可以保持很長(zhǎng)時(shí)間而不會(huì)消退,。成癮大鼠于戒斷嗎啡后再次會(huì)到原來的給藥環(huán)境,，其原來關(guān)于藥物的記憶就可以被喚起。經(jīng)過研究發(fā)現(xiàn),， 在大鼠成癮記憶被喚起后,，給于強(qiáng)烈的冰水應(yīng)激，可以破壞成癮記憶的再鞏固,，從而使原來的記憶消失,。
進(jìn)一步的研究發(fā)現(xiàn)，冰水應(yīng)激誘導(dǎo)的成癮記憶的消失是通過體內(nèi)應(yīng)激激素皮質(zhì)酮介導(dǎo)的,，因?yàn)榻o大鼠注射皮質(zhì)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(zhǎng)時(shí)間而不能恢復(fù)。如果應(yīng)激前給予皮質(zhì)酮合成抑制劑美替拉酮,，能夠阻斷應(yīng)激對(duì)藥物記憶再鞏固的損害作用,。 使用神經(jīng)核團(tuán)微注射技術(shù)，王曉藝等人還發(fā)現(xiàn),，應(yīng)激誘導(dǎo)成癮記憶的破壞主要是由基底外側(cè)杏仁核糖皮質(zhì)激素受體介導(dǎo)的,。大腦結(jié)構(gòu)中的杏仁核是控制情緒和應(yīng)急反應(yīng)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(yīng)用價(jià)值,。吸毒病人出戒毒所后,，雖然生理上恢復(fù)正常，暫時(shí)脫離毒品,，但對(duì)過去吸毒時(shí)愉快記憶仍然強(qiáng)烈,，在社會(huì)上很容易再次吸毒。如果有藥物和一些醫(yī)學(xué)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(jīng)常復(fù)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.
