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.