Indomethacin Partially Alleviates Depressive-Like Behaviors in Maternally Separated Mice: Targeting Neuroinflammatory Response in the Hippocampus

Abstract

Experiencing early-life stress (ELS) plays a fundamental role in the development of mood disorders like depression in adulthood. Neuro-immune response in the brain is coupled with depressive-like behaviors following maternal separation (MS) stress. Indomethacin (IND) is a nonsteroidal anti-inflammatory drug. This study aimed to assess the antidepressant-like effect of IND in a mouse model of MS stress, focusing on its potential effect on neuro-inflammatory response in the hippocampus. To do this, male NMRI mice were treated with IND at doses of 5, 10, and 20 mg/kg, saline (10 mL/kg) or fluoxetine (30 mg/kg). Drugs were injected intraperitoneally for 7 days. Behavioral tests including forced swimming test, splash test, and open field test were performed. Quantitative reverse transcription-PCR was used for evaluation of gene expression of inflammatory mediators including of iNOS, TLR4, NLRP3, TNF-α, and IL-1β in the hippocampus. Results showed that MS provoked depressive-like behavior in mice as observed by a decrease in the grooming activity time in the splash test and an increase in the immobility time in the forced swimming test. Depressive-like behaviors were coupled with neuroinflammation in the hippocampus. IND attenuated depressive-like behaviors as well as decreased the gene expression of neuroinflammation-related mediators in the hippocampus of MS mice. In conclusion, results showed that IND, at least in part, via alleviation of neuro-inflammatory response in the hippocampus, exerted antidepressant-like effects in a mouse model of MS stress.