EFFECT OF MINOCYCLINE AND MINOSCYCLINE+METFORMIN ON DIABETES-RELATED DEPRESSION

Abstract

Objective: Minocycline is a second-generation tetracycline group antibiotic that acts on the central nervous system. Minocycline reduces microglial activation and has anti-inflammatory, anti-apoptotic, and antioxidant properties. Recently, it has been proposed that there is a bidirectional relationship between diabetes and depression and that inflammation is one of the common pathways in their pathophysiology. The effects of minocycline on depression were then investigated. This study aimed to reveal the effects of minocycline alone or in combination with metformin, which is used in the treatment of diabetes, on diabetes-related depression. Material and Method: For this purpose, to establish a human-like type 2 diabetes model in mice, streptozotocin (STZ) (50mg/kg) was administered once a day for five consecutive days after a 4-week high-fat diet. Animals with blood glucose levels ≥200 mg/dl were considered diabetic and employed in this experiment. Minocycline (40 mg/kg), fluoxetine (20 mg/kg), and metformin (200 mg/kg) were given once a day for 7 days two weeks after STZ injection. After the drug injections were completed, an open field test was used to determine locomotor activity and a forced swimming test was used to determine depression level. Result and Discussion: It was concluded that diabetes and the drugs administered did not induce a significant change in locomotor activity, and that the minocycline and minocycline-metformin combination was at least as effective as fluoxetine in treating depression. It is recognized that the initiation of antidepressant effects in a short period is critical for patient adherence to therapy and diabetes prognosis. In conclusion, antidepressant-like effects of subchronic minocycline treatment appear to be potent as classical antidepressants. The mechanisms underlying minocycline's effects on mood should be broadly investigated to increase our understanding of depression and unveil potential novel therapies in depression management.