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Toxic effect of calcium/calmodulin kinase II on anxiety behavior, neuronal firing and plasticity in the male offspring of morphine-abstinent rats.
Behavioural Brain Research ( IF 2.7 ) Pub Date : 2020-08-22 , DOI: 10.1016/j.bbr.2020.112877
Haniyeh Soltani 1 , Mitra-Sadat Sadat-Shirazi 2 , Bahareh Pakpour 1 , Ghorbangol Ashabi 3 , Mohammad-Reza Zarrindast 4
Affiliation  

Studies have shown that epigenetic changes such as alteration in histone acetylation and DNA methylation in various brain regions play an essential role in anxiety behavior. According to the critical role of calcium/calmodulin protein kinaseII (CaMKII) in these processes, the present study examined the effect of CaMKII inhibitor (KN93) on neuronal activity and level of c-fos in the amygdala and nucleus accumbens (NAC) in the offspring of morphine-exposed parents.

Adult male and female Wistar rats received morphine orally (for 21 days). After the washout period (10 days), rats were mated with either drug-naïve or morphine-exposed rats. KN93 was microinjected into the brain of male offspring. The anxiety-like behavior, the neuronal firing rate in the NAC and the amygdala and level of c-fos were assessed by related techniques.

Data showed the offspring with one and/or two morphine-abstinent parent(s) had more anxiety-like behavior than the control group. However, the administration of KN-93 decreased anxiety in the offspring of morphine-exposed rats compared with saline-treated groups. The expression level of the c-fos was not significantly altered by the inhibition of CaMKII in the amygdala, but the c-fos level was reduced in the NAC. The neuronal firing rate of these groups was associated with an increase in the amygdala in comparison to the saline groups but was decreased in the NAC.

Results showed that CaMKII had a role in anxiety-like behavior in the offspring of morphine-exposed parents, and changes in neuronal firing rate and c-fos level in the NAC might be involved in this process.



中文翻译:

钙/钙调蛋白激酶 II 对吗啡戒断大鼠雄性后代的焦虑行为、神经元放电和可塑性的毒性作用。

研究表明,表观遗传变化,例如不同大脑区域的组蛋白乙酰化和 DNA 甲基化的改变,在焦虑行为中起着至关重要的作用。根据钙/钙调蛋白蛋白激酶 II (CaMKII) 在这些过程中的关键作用,本研究检测了 CaMKII 抑制剂 (KN93) 对杏仁核和伏隔核 (NAC) 中神经元活动和 c-fos 水平的影响。吗啡暴露父母的后代。

成年雄性和雌性 Wistar 大鼠口服吗啡(21 天)。清除期(10 天)后,大鼠与未接触药物或接触吗啡的大鼠交配。KN93被显微注射到雄性后代的大脑中。通过相关技术评估焦虑样行为、NAC 和杏仁核中的神经元放电率和 c-fos 水平。

数据显示,有一个和/或两个吗啡禁欲父母的后代比对照组有更多的焦虑样行为。然而,与盐水治疗组相比,KN-93 的给药降低了吗啡暴露大鼠后代的焦虑。c-fos 的表达水平没有因杏仁核中 CaMKII 的抑制而显着改变,但 NAC 中的 c-fos 水平降低。与盐水组相比,这些组的神经元放电率与杏仁核的增加有关,但在 NAC 中却降低了。

结果表明,CaMKII 在吗啡暴露父母的后代的焦虑样行为中起作用,并且 NAC 中神经元放电率和 c-fos 水平的变化可能与此过程有关。

更新日期:2020-08-28
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