Effects of mood stabilizer lithium on noradrenergic turnover in the prefrontal cortex of chronically stressed rats.
Pub Date : 2021-07-01
Ljubica Gavrilovic, Nataša Popović, Vesna Stojiljković, Snežana Pejić, Ana Todorović, Ivan Pavlović, Marija Pantelić, Snežana B Pajović
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Abstract
Objective: Data about the dynamics of noradrenaline (NA) transmission, storage and degradation may be very important for understanding the reduction of functional deficiency of NA and maintaining the stability of NA levels in animals with depressive-like behavior treated with lithium. This study aimed to investigate the effects of mood stabilizer lithium on concentrations of NA in the prefrontal cortex (PFC), as well as behavior rats exposed to chronic restraint stress (CRS). In addition, this study examined the effects of lithium on protein levels of noradrenaline transporter (NET), vesicular monoamine transporter 2 (VMAT2) and catechol-O-methyltransferase (COMT), as well as the enzyme activity of monoamine oxidase A (MOA) in the PFC of chronically stressed rats.
Methods: The investigated parameters were quantified by Western blot analysis, CAT Research ELISA kits, and an assay of enzyme activity. Also, the forced swim test (FST) was used to assess the behavior of animals.
Results: We found that lithium treatment decreased high protein levels of NET and VMAT2, as well as the enzyme activity of MOA in chronically stressed rats to the levels found in unstressed animals. In addition, lithium treatment decreased the concentration of NA (24%) and immobility in animals exposed to CRS.
Conclusion: Our data confirm that lithium-induced modulation of prefrontal noradrenergic turnover and stabilized the behavior of chronically stressed rats.
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情绪稳定剂锂对慢性应激大鼠前额皮质去甲肾上腺素能转换的影响。
目的:研究去甲肾上腺素(NA)传递、储存和降解的动态变化,对了解锂治疗抑郁样行为动物NA功能缺陷的减轻和NA水平的稳定具有重要意义。本研究旨在探讨情绪稳定剂锂对暴露于慢性约束应激(CRS)大鼠前额叶皮质(PFC) NA浓度和行为的影响。此外,本研究还检测了锂对慢性应激大鼠PFC中去甲肾上腺素转运蛋白(NET)、水泡单胺转运蛋白2 (VMAT2)和儿茶酚- o -甲基转移酶(COMT)蛋白水平以及单胺氧化酶A (MOA)酶活性的影响。方法:采用Western blot法、CAT Research ELISA试剂盒和酶活性测定法对研究参数进行定量分析。同时,采用强迫游泳试验(FST)来评估动物的行为。结果:我们发现,锂处理降低了长期应激大鼠的高蛋白水平的NET和VMAT2,以及MOA酶活性,使其降至非应激动物的水平。此外,锂处理降低了暴露于CRS动物的NA浓度(24%)和不动能力。结论:我们的数据证实了锂诱导的慢性应激大鼠前额叶去甲肾上腺素能转换的调节和稳定行为。