Regulation of glutamate transporter 1 (GLT-1) gene expression by cocaine self-administration and withdrawal.
Regulation of glutamate transporter 1 (GLT-1) gene expression by cocaine self-administration and withdrawal.
复制标题
DOI：
10.1016/j.neuropharm.2017.09.019
复制
发表时间：
2018-01
影响因子：
4.7
通讯作者：
Reissner KJ
中科院分区：
文献类型：
--
作者：
Kim R;Sepulveda-Orengo MT;Healey KL;Williams EA;Reissner KJ
在多种滥用药物给药后，在中脑核（NAc）中观察到星形胶质细胞谷氨酸转运蛋白GLT-1的下调。可卡因自我给药后GLT-1蛋白表达的减少取决于可卡因自我给药的量和戒断时间的长短，更长时间获得可卡因和更长的戒断时间导致GLT-1蛋白的更大减少。然而，可卡因下调GLT-1蛋白的机制仍然未知。我们使用qRT-PCR来检测GLT-1剪接异构体（GLT-1A、GLT-1B）在大鼠NAc、前边缘皮层（PL）和基底外侧杏仁核（BLA）中的基因表达，遵循两种广泛使用的可卡因自我给药模型：短通路（ShA）自我给药和长通路（LgA）自我给药/孵育模型。虽然在ShA可卡因自我给药和消退后观察到GLT-1蛋白的下调，但该模型并未导致检查的任何脑区域中GLT-1A或GLT-1B基因表达的变化。ShA可卡因自我给药后的强制禁欲也没有效果。相反，LgA可卡因自我管理和长期禁欲显着降低GLT-1A基因表达的NAc和BLA，并显着降低GLT-1B基因表达的PL。LgA可卡因自我给药后1天，NAc GLT-1A基因表达未观察到变化，表明戒断诱导GLT-1A mRNA降低。此外，LgA可卡因自我管理和戒断诱导NAc中GLT-1基因的高甲基化。这些结果表明，NAc GLT-1 mRNA的减少仅在长期接触可卡因并长期禁欲后观察到，并且表观遗传机制可能有助于这种效应。
Downregulation of the astroglial glutamate transporter GLT-1 is observed in the nucleus accumbens (NAc) following administration of multiple drugs of abuse. The decrease in GLT-1 protein expression following cocaine self-administration is dependent on both the amount of cocaine self-administered and the length of withdrawal, with longer access to cocaine and longer withdrawal periods leading to greater decreases in GLT-1 protein. However, the mechanism(s) by which cocaine downregulates GLT-1 protein remains unknown. We used qRT-PCR to examine gene expression of GLT-1 splice isoforms (GLT-1A, GLT-1B) in the NAc, prelimbic cortex (PL) and basolateral amygdala (BLA) of rats, following two widely used models of cocaine self-administration: short-access (ShA) self-administration, and the long-access (LgA) self-administration/incubation model. While downregulation of GLT-1 protein is observed following ShA cocaine self-administration and extinction, this model did not lead to a change in GLT-1A or GLT-1B gene expression in any brain region examined. Forced abstinence following ShA cocaine self-administration also was without effect. In contrast, LgA cocaine self-administration and prolonged abstinence significantly decreased GLT-1A gene expression in the NAc and BLA, and significantly decreased GLT-1B gene expression in the PL. No change was observed in NAc GLT-1A gene expression one day after LgA cocaine self-administration, indicating withdrawal-induced decreases in GLT-1A mRNA. In addition, LgA cocaine self-administration and withdrawal induced hypermethylation of the GLT-1 gene in the NAc. These results indicate that a decrease in NAc GLT-1 mRNA is only observed after extended access to cocaine combined with protracted abstinence, and that epigenetic mechanisms likely contribute to this effect.
登录
查看更多内容
影响因子：
3.7
作者：
LaRowe, SD;Mardikian, P;Brady, K
通讯作者：
Brady, K
DOI：
10.1523/jneurosci.3278-12.2013
发表时间：
2013-05-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fischer KD;Houston AC;Rebec GV
通讯作者：
Rebec GV
影响因子：
3.4
作者：
Fuchs, Rita A.;Eaddy, Jessica L.;Bell, Guinevere H.
通讯作者：
Bell, Guinevere H.
影响因子：
4.7
作者：
Ibanez, Ignacio;Javier Diez-Guerra, F.;Zafra, Francisco
通讯作者：
Zafra, Francisco
影响因子：
25
作者：
Baker, DA;McFarland, K;Kalivas, PW
通讯作者：
Kalivas, PW