Influence of 5-HT2A receptor function on anxiety-like behavior induced by combination treatment with doxorubicin and cyclophosphamide in rats
Influence of 5-HT2A receptor function on anxiety-like behavior induced by combination treatment with doxorubicin and cyclophosphamide in rats
复制标题
5-HT2A受体功能对阿霉素与环磷酰胺联合治疗大鼠焦虑样行为的影响
DOI：
10.1007/s00213-021-05979-5
复制
发表时间：
2021
影响因子：
3.4
通讯作者：
Sendo T.
中科院分区：
文献类型：
--
作者：
Tabuchi H;Kitamura Y;Ushio S;Kan S;Wada Y;Sumiyoshi Y;Izushi Y;Miyazaki I;Asanuma M;Sendo T.
阿霉素和环磷酰胺联合用药引起的焦虑样行为可能是由血清素 (5-HT)2A 受体过度活跃介导的。这种组合可能会抑制氟西汀的抗焦虑作用。本研究探讨了阿霉素和环磷酰胺联合用药引起大鼠焦虑样行为的机制。在明暗测试中，阿霉素和环磷酰胺治疗（每周一次，持续两周）诱导了类似焦虑的行为。使用蛋白质印迹法测量 5-HT2A 受体和 5-HT2A 受体介导的细胞外信号相关激酶 (ERK)1/2 水平。还使用微透析检查了氟西汀治疗大鼠的 5-HT 再摄取活性。 ( ±)-1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷是一种 5-HT2A 受体激动剂，可诱导焦虑样行为。氟西汀治疗增加了媒介物、阿霉素和环磷酰胺治疗的大鼠海马细胞外 5-HT 浓度。海马中的 5-HT 转运蛋白水平不受化疗影响。阿霉素和环磷酰胺治疗不会改变额叶皮质中的 5-HT2A 受体水平。然而，化疗使 5-HT2A 受体介导的 ERK1/2 磷酸化水平显着高于载体治疗。目前的结果表明，多柔比星和环磷酰胺组合诱导的焦虑样行为是由 5-HT2A 受体过度活跃介导的，而不增加大鼠中 5-HT2A 受体水平。
Anxiety-like behavior induced by a combination of doxorubicin and cyclophosphamide may be mediated by serotonin (5-HT)2Areceptor hyperactivity. The anxiolytic effects of fluoxetine may be inhibited by this combination. The present study examined the mechanisms underlying anxiety-like behavior induced by the combination doxorubicin and cyclophosphamide in rats. Anxiety-like behavior was induced during a light–dark test by the doxorubicin and cyclophosphamide treatment (once a week for 2 weeks). 5-HT2Areceptor and 5-HT2Areceptor-mediated extracellular signal-related kinase (ERK)1/2 levels were measured using Western blotting. 5-HT reuptake activity in fluoxetine-treated rats was also examined using microdialysis. ( ±)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane, a 5-HT2Areceptor agonist, induced anxiety-like behavior. The fluoxetine treatment increased extracellular 5-HT concentrations in the hippocampus of vehicle- and doxorubicin and cyclophosphamide-treated rats. 5-HT transporter levels in the hippocampus were not affected by chemotherapy. The doxorubicin and cyclophosphamide treatment did not alter 5-HT2Areceptor levels in the frontal cortex. However, chemotherapy increased 5-HT2Areceptor-mediated ERK1/2 phosphorylation levels significantly more than the vehicle treatment. The present results suggest that anxiety-like behavior induced by the combination of doxorubicin and cyclophosphamide is mediated by 5-HT2Areceptor hyperactivity without an increase in 5-HT2Areceptor levels in rats.