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.