Expression analysis of hippocampal and amygdala CREB-BDNF signaling pathway in nicotine-induced reward under stress in rats
Expression analysis of hippocampal and amygdala CREB-BDNF signaling pathway in nicotine-induced reward under stress in rats
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DOI：
10.1016/j.brainres.2020.146885
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发表时间：
2020-08-15
期刊：
影响因子：
2.9
通讯作者：
Rezayof, Ameneh
中科院分区：
文献类型：
--
作者：
Ghasemzadeh, Zahra;Sardari, Maryam;Rezayof, Ameneh
大量的研究表明，个体在压力状态下更容易成瘾和吸毒。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）激活尼古丁诱导的条件性位置偏爱（CPP）暴露于急性或亚慢性应激下的可能作用。使用蛋白质印迹技术，CREB磷酸化增加，在海马和杏仁核尼古丁诱导的CPP。在尼古丁给药后和暴露于急性应激的尼古丁治疗动物中，海马BDNF水平增加。在暴露于急性应激的动物中，pCREB/CREB的杏仁核比率降低，而用尼古丁（0.1 mg/kg）预处理的动物仅在海马中降低了该比率。亚慢性应激降低海马和杏仁核中的pCREB/CREB比值。有趣的是，亚慢性应激诱导的尼古丁奖赏增加只降低海马pCREB/CREB比值。急性应激时海马和杏仁核中BDNF的水平下降。急性应激引起的尼古丁奖励增加增加了海马中的BDNF水平。此外，动物暴露于CPP装置而没有任何药物给药增加了靶位点中pCREB/tCREB和BDNF/β-肌动蛋白的比率。综上所述，本研究提示应激条件下海马内pCREB/CREB比值的改变以及BDNF水平的改变可能是增强尼古丁奖赏效应的关键。这项研究的证据表明，海马体和杏仁核在压力下介导尼古丁奖励中发挥着不同的作用。
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/beta-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.