Effects of protracted nicotine exposure and withdrawal on the expression and phosphorylation of the CREB gene transcription factor in rat brain
Effects of protracted nicotine exposure and withdrawal on the expression and phosphorylation of the CREB gene transcription factor in rat brain
复制标题
DOI：
10.1046/j.1471-4159.2001.00309.x
复制
发表时间：
2001-05-01
影响因子：
4.7
通讯作者：
Mittal, N
中科院分区：
文献类型：
--
作者：
Pandey, SC;Roy, A;Mittal, N
尼古丁成瘾可能通过环腺苷酸反应元件结合蛋白（CREB）依赖性基因转录程序的变化导致特定脑结构神经回路的分子适应。因此，我们研究了慢性尼古丁暴露及其戒断对大鼠脑中CREB和磷酸化CREB（p-CREB）蛋白水平的影响。我们在这里报告，慢性尼古丁暴露（l-h戒断）对大鼠皮质和杏仁核中CREB和p-CREB的表达没有影响。另一方面，减少CREB蛋白的表达和磷酸化的CREB发生在扣带回，并在顶叶和梨状，但不是在额叶皮层尼古丁戒断（18小时）尼古丁暴露后。还观察到，CREB和p-CREB蛋白水平显着下降，在内侧和基底外侧，但不是在中央杏仁核尼古丁戒断（18小时）慢性尼古丁暴露后。此外，发现慢性尼古丁暴露后尼古丁戒断（18小时）导致CRE-DNA结合减少，而不调节大鼠皮质和杏仁核中cAMP依赖性蛋白激酶A活性。此外，通过高架十字迷宫试验测定，慢性尼古丁给药产生抗焦虑作用，而尼古丁戒断（18 h）在大鼠中产生焦虑。这些结果提供了第一个证据表明，减少CREB活性和/或表达在特定的皮质和杏仁脑结构可能参与尼古丁依赖的潜在分子机制。
Addiction to nicotine may result in molecular adaptations in the neurocircuitry of specific brain structures via changes in the cyclic AMP-responsive element binding protein (CREB)-dependent gene transcription program. We therefore investigated the effects of chronic nicotine exposure and its withdrawal on CREB and phosphorylated CREB (p-CREB) protein levels in the rat brain. We report here that chronic nicotine exposure (l-h withdrawal) had no effect on the expression of CREB and p-CREB in the rat cortex and amygdala. On the other hand, decreases in the expression of CREB protein and phosphorylation of CREB occur in the cingulate gyrus, and in the parietal and the piriform but not in the frontal cortex during nicotine withdrawal (18 h) after nicotine exposure. It was also observed that CREB and p-CREB protein levels were significantly decreased in the medial and basolateral, but not in the central amygdala during nicotine withdrawal (18 h) after chronic nicotine exposure. Furthermore, it was found that nicotine withdrawal (18 h) after chronic nicotine exposure leads to decreased CRE-DNA binding without modulating cAMP-dependent protein kinase A activity in the cortex and the amygdala of rats. In addition, chronic nicotine treatment produced anxiolytic effects whereas nicotine withdrawal (18 h) produced anxiety in rats as measured by the elevated plus-maze test. These results provide the first evidence that decreased CREB activity and/or expression in specific cortical and amygdaloid brain structures may be involved in the underlying molecular mechanisms of nicotine dependence.