minocycline prevents depression-like behavior after co-administration with dexamethasone or cyclosporine-a in mice

Background: in animal studies, minocycline (mcy) has been proven to have antidepressant effects. in addition to modulating peripheral and central pro-inflammatory pathways, mcy may regulate the hypothalamic-pituitary-adrenal (hpa) axis and the mechanistic target of rapamycin (mtor) signaling pathway. this study aims to evaluate the antidepressant-like effect of mcy in mice following injection of dexamethasone (dex) or cyclosporine-a (csa). methods: male nmri mice were randomly divided into eight groups of 6, including control, dex 0.25 mg/kg, csa 20 mg/kg, mcy 40 mg/kg, dex+mcy, dex+fluoxetine 20 mg/kg, csa+mcy, and csa+fluoxetine. all drugs were injected intraperitoneally (except for dex, which was subcutaneous injection) once daily for 3 days. the locomotor activity, forced swimming test (fst), and sucrose preference (sp) test were performed on day 4. results: mcy alone reduced immobility time in the fst (27.0±6.4 s) compared to the control group (104±3.9 s) (p<0.001). after the co-administration of mcy and dex, the immobility time significantly decreased (79.5±6.5 s) compared to the dex group (p<0.001). it also decreased following the co-administration of mcy and csa (67.5±20.8 s) compared to the csa group (p<0.001). results were similar in the groups treated with fluoxetine plus dex or csa. significant differences were not observed in the locomotor activity test. conclusion: mcy prevents depression-like behavior in mice during the fst when it is co-administrated with csa or dex. the possibility of the positive effect of mcy on the hpa axis and the mtor signaling pathway should be examined in further studies.