Ondansetron ameliorates depression associated with obesity in high-fat diet fed experimental mice: An investigation-based on the behavioral, biochemical, and molecular approach.

introductionObesity is an important risk factor for depression as more than half of the obese population is susceptible for depression at double rate. Our earlier studies reported the antidepressant potential of 5-HT MATERIALS AND

methodsMice were fed with high-fat diet (HFD) for 14 weeks, followed by treatment schedule for 28 days with vehicle/OND (0.5 and 1 mg/kg, p.o.)/reference antidepressant escitalopram (10 mg/kg, p.o.). Subsequently, animals were screened in the behavioral tests of depression such as forced swim test (FST) and sucrose preference test (SPT), biochemical estimations including hippocampal cAMP, BDNF and 5-HT, and molecular assays mainly histology and p53 expression of dentate gyrus (DG).

resultsHFD-fed mice showed increased immobility time in FST, reduced sucrose consumption in SPT, decreased level of signal transduction factor cAMP, neuronal growth factor BDNF and neurotransmitter 5-HT in the hippocampus, and raised and p53 expression neuronal damage in the DG region of mice fed with HFD in comparison to the mice fed with normal pellet diet. Chronic treatment with OND (0.5 and 1 mg/kg, p.o.) significantly inhibited the behavioral, biochemical and molecular modifications in HFD-fed mice.

conclusionIn the preliminary study, OND attenuated depression associated with obesity in mice fed with HFD using various assays procedures, at least in part by the modulation of serotonergic transmission.