Involvement of 5-HT2A receptor hyperfunction in the anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment in rats

Yuka Nakamura, Yoshihisa Kitamura, Yusuke Sumiyoshi, Nanami Naito, Shiho Kan, Soichiro Ushio, Ikuko Miyazaki, Masato Asanuma, Toshiaki Sendo

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 light–dark 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.

Original languageEnglish
Pages (from-to)192-197
Number of pages6
JournalJournal of Pharmacological Sciences
Volume138
Issue number3
DOIs
Publication statusPublished - Nov 2018

Keywords

  • 5-HT receptor
  • Anxiety
  • Cyclophosphamide
  • Doxorubicin

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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