Influence of 5-HT 2A receptor function on anxiety-like behavior induced by a combination treatment with doxorubicin and cyclophosphamide in rats

• Published in: Psychopharmacology (Berlin, Germany) Vol. 238; no. 12; p. 3607
• Main Authors: Tabuchi, Hironori, Kitamura, Yoshihisa, Ushio, Soichiro, Kan, Shiho, Wada, Yudai, Sumiyoshi, Yusuke, Izushi, Yasuhisa, Miyazaki, Ikuko, Asanuma, Masato, Sendo, Toshiaki
• Format: Journal Article
• Language: English
• Published: Germany 01-12-2021
• Subjects: Animals; Anxiety - chemically induced; Cyclophosphamide - toxicity; Doxorubicin; Rats; Receptor, Serotonin, 5-HT2A; Serotonin; 5-HT2A receptor; Cyclophosphamide; Fluoxetine; Anxiety; Doxorubicin
• ISSN: 1432-2072

Anxiety-like behavior induced by a combination of doxorubicin and cyclophosphamide may be mediated by serotonin (5-HT)
receptor 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-HT
receptor and 5-HT
receptor-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-HT
receptor 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-HT
receptor levels in the frontal cortex. However, chemotherapy increased 5-HT
receptor-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-HT
receptor hyperactivity without an increase in 5-HT
receptor levels in rats.