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    EFFECT OF MINOCYCLINE AND MINOSCYCLINE+METFORMIN ON EXPERIMENTAL DIABETES-RELATED DEPRESSION
    (University of Ankara, 2022) İNci? Çamçi M.; Erdi?Nç M.; Uyar E.; Kelle İ.
    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. © 2022 University of Ankara. All rights reserved.
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    THE EFFECTS OF MELATONIN, FLUOXETINE AND THEIR COMBINATIONS ON STRESS-INDUCED BEHAVIORAL AND COGNITIVE IMPAIRMENTS IN MICE
    (University of Ankara, 2022) İncı Çamçı M.; Erdi?nç M.; Kelle İ.; Uyar E.; Erdınç L.
    Objective: Melatonin (Mlt) is a hormone with antidepressant and antioxidant features. It is well known that Mlt protects brain cells from reactive oxygen species and that the brain's high oxygen consumption and lipid content make it particularly vulnerable to oxidative stress caused by prolonged stress. This study aims to investigate the effects of melatonin, fluoxetine (Flx) and their combinations on emotional memory, depression, and anxiety-like behavioral changes induced by immobilization (Imb) stress. Material and Method: 48 male Balb/c mice were divided into eight groups: Cnt (control), Imb, Imb+Mlt, Imb+Flx, Imb+Mlt+Flx, Mlt, Flx and Mlt+Flx. For seven days in a row, the mice underwent daily immobilization stress for 6 hours. Mice were treated with Mlt (10 mg/kg) and Flx (20 mg/kg) or saline 30 min prior to the immobilization stress procedure. All animals were subjected to behavioral tests; forced swimming test (FST), open field test (OFT), elevated plus maze (EPM), passive avoidance test (PAT), and hot plate (HP) test. After all behavioral tests, brain tissues were obtained for malondialdehyde (MDA) level analysis. Result and Discussion: OFT test data showed the time spent in the central zone and the number of entrances to the central area were lower in the Imb group compared to the Cnt group; these were higher in the Imb+Flx, Imb+Mlt, Imb+Mlt+Flx groups compared to the Imb group. Also, according to the data obtained from FST, immobile time was significantly higher in the Imb group compared to the Cnt group, and it was lower in the Imb+Flx, Imb+Mlt, Imb+Mlt+Flx groups compared to the Imb group. Besides, it was demonstrated that the emotional memory index was statistically higher in the Imb group compared to the Cnt group, and the increasing of memory index returned to normal in the Imb+Mlt and Imb+Mlt+Flx groups with PAT. Furthermore, lipid peroxidation level, which increased in the Imb group, decreased significantly in the Imb+Flx, Imb+Mlt, and Imb+Mlt+Flx groups. As a result, it was observed that melatonin has antidepressant, anxiolytic, antioxidant effects and normalized emotional memory. Also, melatonin, fluoxetine, and their combinations exert similar effects in the present study. © 2022 University of Ankara. All rights reserved.