Evaluation of the effects of melatonin and ramelteon in A rat posttraumatic stress model

Post-traumatic stress disorder (PTSD) is an important psychiatric disorder, and it is a common disorder that can develop after experiencing or witnessing traumatic events. Some of the side symptoms of PTSD, such as sleep disturbance, can be particularly difficult to treat and may require the use of multiple medications common in the treatment of PTSD. There are a very limited number of studies on the role of melatonin, a hormone secreted from the pineal gland, in the etiology of PTSD and the possible efficacy of melatonin and the approved melatonin receptor agonist ramelteon in the treatment of sleep disorders. In this study, it was aimed to investigate the efficacy of melatonin and ramelteon in the PTSD model created in pinealectomy and non-pinealectomy rats. For this purpose, after the PTSD model was created, the results of behavioral experiments were evaluated and brain-derived neurotrophic factor (BDNF), pro-brain-derived neurotrophic factor (pro-BDNF), corticotropin-releasing hormone (CRH) and tropomyosin receptor kinase (TrkB) in brain tissue were analyzed by immunohistochemistry and Elisa methods, which are thought to be associated with PTSD. Pinealectomy, which is known to significantly reduce melatonin levels in rats, caused a significant increase in stress and anxiety when behavioral tests, biochemistry and immunohistochemistry findings were evaluated together. This finding is important in that there is no study in the literature on the increase in stress and anxiety due to the decrease in physiological melatonin levels as a result of pinealectomy. Again, when all parameters were evaluated together, a greater increase in stress-related anxiety in pinealectomized rats could not be detected for many parameters except the time spent in the open arm in the elevated plus maze (EPM) test, and the beneficial effects of melatonin and ramelteon were also limited. In rats that did not undergo pinealectomy surgery, an increase in stress-related anxiety was observed in the EPM test; melatonin and especially ramelteon have been found to be partially successful in reversing this effect. In the biochemical analyzes performed in the hippocampus, an increasing trend was detected in stress-related anxiety; melatonin and ramelteon reversed this effect. In immunohistochemistry analyses, an increase in stress-related anxiety was observed in some parameters; melatonin and ramelteon reversed this effect. In conclusion, in this study, it was shown that the increase in stress-related anxiety in the rat PTSD model can be partially prevented by melatonin and ramelteon. Another important finding is that the decrease in physiological concentrations of melatonin may cause anxiety and melatonin and ramelteon may be partially beneficial. Key words: Post-traumatic stress disorder, rat, pinealectomy, melatonin, ramelteon