Involvement of 5-HT 2A receptor hyperfunction in the anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment in rats

• Published in: Journal of pharmacological sciences Vol. 138; no. 3; p. 192
• Main Authors: Nakamura, Yuka, Kitamura, Yoshihisa, Sumiyoshi, Yusuke, Naito, Nanami, Kan, Shiho, Ushio, Soichiro, Miyazaki, Ikuko, Asanuma, Masato, Sendo, Toshiaki
• Format: Journal Article
• Language: English
• Published: Japan 01-11-2018
• Subjects: 5-HT(2A) receptor; Cyclophosphamide; Anxiety; Doxorubicin
• ISSN: 1347-8648

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)
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-HT
receptor-mediated behavioral responses. Combination treatment with doxorubicin and cyclophosphamide significantly increased (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, (a 5-HT
receptor agonist)-induced wet-dog shake activity. This anxiety-like behavior was significantly inhibited by mirtazapine, a 5-HT
receptor antagonist/5-HT
receptor agonist, and tandospirone, a partial 5-HT
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-HT
receptor. Thus, 5-HT
receptor antagonists or 5-HT
receptor agonists might be useful for treating chemotherapy-induced anxiety disorders.