Involvement of 5-HT2A receptor hyperfunction in the anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment in rats
Involvement of 5-HT2A receptor hyperfunction in the anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment in rats
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DOI：
10.1016/j.jphs.2018.10.001
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发表时间：
2018-11-01
影响因子：
3.5
通讯作者：
Sendo, Toshiaki
中科院分区：
文献类型：
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作者：
Nakamura, Yuka;Kitamura, Yoshihisa;Sendo, Toshiaki
我们研究了多柔比星和环磷酰胺（一种传统的乳腺癌化疗药物）联合治疗是否会诱导大鼠的焦虑样行为。此外，我们评估了5-羟色胺（5-HT）（2A）受体亚型在化疗诱导的焦虑样行为中的作用。大鼠腹腔注射阿霉素和环磷酰胺，每周一次，持续2周。这导致老鼠在明暗测试中表现出焦虑样行为。此外，我们还检测了大鼠5-HT 2A受体介导的行为反应。多柔比星和环磷酰胺联合治疗显著增加（+/-）-1-（2，5-二甲氧基-4-碘苯基）-2-氨基丙烷（5-HT 2A受体激动剂）诱导的湿狗抖动活性。这种焦虑样行为被米氮平（一种5-HT 2A受体拮抗剂/5-HT 1A受体激动剂）和坦度螺酮（一种5-HT 1A受体部分激动剂）显著抑制，但不被氟西汀（一种选择性5-羟色胺再摄取抑制剂）抑制。阿霉素和环磷酰胺联合治疗诱导的焦虑样行为是由5-HT 2A受体功能亢进介导的。因此，5-HT 2A受体拮抗剂或5-HT 1A受体激动剂可用于治疗化疗诱导的焦虑症。(c)2018作者Elsevier B. V.代表日本药理学会制作和主办。这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
We examined whether combination treatment with doxorubicin and cyclophosphamide, a traditional chemotherapy for breast cancer, induced anxiety-like behavior in rats. Furthermore, we evaluated the role of the serotonin (5-HT)(2A) receptor subtype in the anxiety-like behavior induced by such chemotherapy. Rats were intraperitoneally injected with doxorubicin and cyclophosphamide once a week for 2 weeks. This caused the rats to display anxiety-like behavior during the lightedark test. In addition, we examined the rats' 5-HT2A receptor-mediated behavioral responses. Combination treatment with doxorubicin and cyclophosphamide significantly increased (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, (a 5-HT2A receptor agonist)-induced wet-dog shake activity. This anxiety-like behavior was significantly inhibited by mirtazapine, a 5-HT2A receptor antagonist/5-HT1A receptor agonist, and tandospirone, a partial 5-HT1A receptor agonist, but not by fluoxetine, a selective serotonin reuptake inhibitor. The anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment is mediated by hyperfunctioning of the 5-HT2A receptor. Thus, 5-HT2A receptor antagonists or 5-HT1A receptor agonists might be useful for treating chemotherapy-induced anxiety disorders. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).