Effects of melatonin and agomelatine on doxorubicin induced anxiety and depression-like behaviors in rats

Abstract

Objective:  Doxorubicin (DOX) is a chemotherapeutic agent used to treat several cancer types; however, it exhibits severe side effects in the nervous system which DOX treatment evoked neurobehavioral alterations such as anxiety and depressive-like behavior. We investigated the use of melatonin and agomelatine to prevent neurobehavioral alterations caused by DOX. Material and Methods: Forty-nine Wistar albino rats were randomly divided into 7 groups, namely control (CON, n=7), doxorubicin (DOX, n=7), melatonin (MEL, n=7), agomelatine (AGO, n=7), melatonin + doxorubicin (MEL + DOX, n=7), agomelatine + doxorubicin (AGO + DOX, n=7) melatonin + agomelatine + doxorubicin (MEL + AGO + DOX, n=7) groups. Doxorubicin (18 mg/kg) was injected intraperitoneally (i.p) on the 5th, 6th, 7th day of the study. Animals were treated with melatonin (40 mg/kg/i.p), agomelatine (40 mg/kg/i.p), melatonin (40 mg/kg/i.p) + agomelatine (40 mg/kg/i.p), for 7 days and then doxorubicin (18 mg/kg/i.p) was injected on the 5th, 6th, 7th day. On the 8th day of the experiment, all animal evaluated open field test (OFT) and forced swim test (FST) respectively. Results: The only DOX-treated rats exhibited the reduced exploration, grooming, and locomotor activity in the open field test and increased immobility time, reduced swimming time. Our data showed that the rats treated with DOX exhibited anxiety and depressive-like behavior. Melatonin and agomelatine treatment reduced all the parameters of DOX-induced anxiety and depressive-like behavior in rats. Conclusions: Melatonin and agomelatine have a protective effect of against DOX-induced neurobehavioral alterations in rats.