en فارماکولوژی Pharmacology پژوهشي Original Research <span style="font-size:14px;"><span style="font-family:Tahoma;"><strong>Background</strong>: 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).&nbsp;<br> <strong>Methods</strong>: 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.&nbsp;<br> <strong>Results</strong>: Mcy alone reduced immobility time in the FST (27.0&plusmn;6.4 s) compared to the control group (104&plusmn;3.9 s) (P<0.001). After the co-administration of Mcy and Dex, the immobility time significantly decreased (79.5&plusmn;6.5 s) compared to the Dex group (P<0.001). It also decreased following the co-administration of Mcy and CsA (67.5&plusmn;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.&nbsp;<br> <strong>Conclusion</strong>: 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.</span></span> Animal experiments, Depression, Minocycline, Dexamethasone, Cyclosporine A 223 230 http://pbr.mazums.ac.ir/browse.php?a_code=A-10-1116-2&slc_lang=en&sid=1 Azadeh Mesripour a_mesripour@pharm.mui.ac.ir 100319475328460010323 100319475328460010323 Yes Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. Sara Pezeshki pezeshki.sara@gmail.com 100319475328460010324 100319475328460010324 No Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.