Extensive research has shown that individuals are more sensitive to develop addiction and drug taking under stress state. The present study includes an expression analysis to identify the possible role of hippocampal and amygdala CREB (cAMP response element-binding protein) and BDNF (Brain-derived neurotrophic factor) activation in nicotine-induced conditioned place preference (CPP) under exposure to acute or sub-chronic stress. Using western-blot technique, CREB phosphorylation was shown to increase in the hippocampus and the amygdala following nicotine-induced CPP. The hippocampal level of BDNF was increased following nicotine administration and in the nicotine-treated animals exposed to acute stress. In animals exposed to acute stress, the amygdala ratios of the pCREB/CREB decreased, while pre-treatment of the animals with nicotine (0.1 mg/kg) decreased this ratio only in the hippocampus. Sub-chronic stress decreased the pCREB/CREB ratios in the hippocampus and the amygdala. Interestingly, sub-chronic stress-induced increase of nicotine reward only decreased the hippocampal pCREB/CREB ratio. The levels of BDNF in the hippocampus and the amygdala decreased under acute stress. Acute stress-induced increase of nicotine reward increased BDNF levels in the hippocampus. Moreover, the animals' exposure to the CPP apparatus without any drug administration increased the ratios of pCREB/tCREB and BDNF/β-actin in the targeted sites. In summary, the present study indicate that the alterations of the ratio of pCREB/CREB and also the level of BDNF in the hippocampus may be critical for enhancing nicotine reward under stress condition. The evidence from this study suggests the distinct roles of the hippocampus and the amygdala in mediating nicotine reward under stress.

中文翻译：

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应激状态下尼古丁诱导奖赏中海马和杏仁核 CREB-BDNF 信号通路的表达分析


广泛的研究表明，个体在压力状态下对成瘾和吸毒更加敏感。本研究包括表达分析，以确定海马和杏仁核 CREB（cAMP 反应元件结合蛋白）和 BDNF（脑源性神经营养因子）激活在尼古丁诱导的条件性位置偏好（CPP）中的可能作用。亚慢性压力。使用蛋白质印迹技术，在尼古丁诱导的 CPP 后，海马和杏仁核中的 CREB ​​磷酸化增加。尼古丁给药后以及暴露于急性应激的接受尼古丁治疗的动物中，海马 BDNF 水平升高。在受到急性应激的动物中，杏仁核 pCREB/CREB ​​的比率下降，而用尼古丁（0.1 mg/kg）预处理的动物仅降低了海马体中的该比率。亚慢性应激降低了海马和杏仁核中的 pCREB/CREB ​​比率。有趣的是，亚慢性应激引起的尼古丁奖励增加仅降低了海马 pCREB/CREB ​​比率。在急性应激下，海马和杏仁核中的 BDNF 水平下降。急性压力引起的尼古丁奖励增加会增加海马体中的 BDNF 水平。此外，动物在不给予任何药物的情况下暴露于 CPP 装置增加了目标位点中 pCREB/tCREB ​​和 BDNF/β-肌动蛋白的比率。总之，本研究表明 pCREB/CREB ​​比率的变化以及海马 BDNF 水平的变化可能对于增强压力条件下的尼古丁奖励至关重要。这项研究的证据表明，海马体和杏仁核在调节压力下的尼古丁奖励方面发挥着独特的作用。