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 language | English |
|---|---|
| Journal | Journal of Pharmacological Sciences |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2018 |
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Keywords
- 5-HT receptor
- Anxiety
- Cyclophosphamide
- Doxorubicin
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
Cite this
Involvement of 5-HT2A receptor hyperfunction in the anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment in rats. / Nakamura, Yuka; Kitamura, Yoshihisa; Sumiyoshi, Yusuke; Naito, Nanami; Kan, Shiho; Ushio, Soichiro; Miyazaki, Ikuko; Asanuma, Masato; Sendo, Toshiaki.
In: Journal of Pharmacological Sciences, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Involvement of 5-HT2A receptor hyperfunction in the anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment in rats
AU - Nakamura, Yuka
AU - Kitamura, Yoshihisa
AU - Sumiyoshi, Yusuke
AU - Naito, Nanami
AU - Kan, Shiho
AU - Ushio, Soichiro
AU - Miyazaki, Ikuko
AU - Asanuma, Masato
AU - Sendo, Toshiaki
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - 5-HT receptor
KW - Anxiety
KW - Cyclophosphamide
KW - Doxorubicin
UR - http://www.scopus.com/inward/record.url?scp=85055081575&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055081575&partnerID=8YFLogxK
U2 - 10.1016/j.jphs.2018.10.001
DO - 10.1016/j.jphs.2018.10.001
M3 - Article
C2 - 30360947
AN - SCOPUS:85055081575
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8648
ER -