Regulation of cocaine reward by CREB
Regulation of cocaine reward by CREB
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DOI：
10.1126/science.282.5397.2272
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发表时间：
1998-12-18
期刊：
影响因子：
56.9
通讯作者：
Nestler, EJ
中科院分区：
文献类型：
--
作者：
Carlezon, WA;Thome, J;Nestler, EJ
辅酶Ⅱ调节大鼠延髓核中的转录因子CREB（腺苷3 '，5'-单磷酸反应元件结合蛋白），这是一个对成瘾很重要的大脑区域。CREB在这个区域的过度表达降低了可卡因的奖励作用，并使低剂量的药物令人厌恶。相反，显性负突变CREB的过度表达增加了可卡因的奖励作用。强啡肽的转录改变可能有助于这些作用：其表达通过CREB的过表达而增加，通过突变型CREB的过表达而减少。此外，阻断强啡肽作用的κ阿片受体可拮抗CREB对可卡因奖赏的负作用。这些结果确定了一个细胞内的级联反应，最终在基因表达，通过暴露于可卡因修改随后对药物的反应。
Cocaine regulates the transcription factor CREB (adenosine 3',5'-monophosphate response element binding protein) in rat nucleus accumbens, a brain region that is important for addiction. Overexpression of CREB in this region decreases the rewarding effects of cocaine and makes Low doses of the drug aversive. Conversely, overexpression of a dominant-negative mutant CREB increases the rewarding effects of cocaine. Altered transcription of dynorphin Likely contributes to these effects: Its expression is increased by overexpression of CREB and decreased by overexpression of mutant CREB. Moreover, blockade of kappa opioid receptors ton which dynorphin acts) antagonizes the negative effect of CREB on cocaine reward. These results identify an intracellular cascade-culminating in gene expression-through which exposure to cocaine modifies subsequent responsiveness to the drug.