cAMP response element-binding protein is required for stress but not cocaine-induced reinstatement
cAMP response element-binding protein is required for stress but not cocaine-induced reinstatement
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DOI：
10.1523/jneurosci.1706-04.2004
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发表时间：
2004-07-28
影响因子：
5.3
通讯作者：
Blendy, JA
中科院分区：
文献类型：
--
作者：
Kreibich, AS;Blendy, JA
应激或药物暴露可诱发先前已消失的条件性位置偏好（CPP）的恢复。在这里，我们表明急性暴露于强迫游泳应激（FS），在不同于条件反射的情况下，诱导野生型小鼠恢复可卡因CPP。这种行为伴随着cAMP反应元件结合蛋白（pCREB）在离散脑区磷酸化的激活模式，这与可卡因诱导恢复后观察到的模式不同。例如，先前的可卡因调节会增加杏仁核中的pCREB水平，而急性暴露于FS而不是可卡因，会进一步增加这些变化。相比之下，先前的可卡因条件作用不会改变伏隔核的pCREB水平，但急性暴露于FS会在恢复当天增加该区域的pCREB水平。此外，为了确定这些CREB的改变在FS或可卡因诱导的恢复中是否必要，我们研究了这些刺激对CREB α和δ亚型缺乏的小鼠恢复行为的影响。CREBalphaDelta突变小鼠在fs诱导的条件位置偏好恢复中表现出缺陷。相比之下，他们表现出强劲的可卡因诱导恢复。这种压力而非药物诱导恢复的缺陷表明，在药物滥用的压力诱导行为反应中，CREB有特定的要求。
Reinstatement of previously extinguished conditioned place preference (CPP) is precipitated by stress or drug exposure. Here, we show that acute exposure to forced swim stress (FS), in a context distinct from conditioning, induces reinstatement of cocaine CPP in wild-type mice. This behavior is accompanied by a pattern of phosphorylated cAMP response element-binding protein (pCREB) activation in discrete brain regions that is distinct from the pattern observed after cocaine-induced reinstatement. For example, previous cocaine conditioning increases pCREB levels in the amygdala, and acute exposure to FS, but not to cocaine, further augments these changes. In contrast, previous cocaine conditioning does not alter levels of pCREB in the nucleus accumbens, but acute exposure to FS increases pCREB levels in this region on reinstatement day. Furthermore, to determine whether these alterations of CREB are necessary in FS or cocaine-induced reinstatement, we examined the effect of these stimuli on reinstatement behavior in mice deficient in alpha and Delta isoforms of CREB. The CREBalphaDelta mutant mice show deficits in FS-induced reinstatement of conditioned place preference. In contrast, they show robust cocaine-induced reinstatement. This deficit in stress but not drug-induced reinstatement indicates a specific requirement for CREB in stress-induced behavioral responses to drugs of abuse.