Melatonin produces a rapid onset and prolonged efficacy in reducing depression-like behaviors in adult rats exposed to chronic unpredictable mild stress.

The present study was aimed at evaluating the rapidity and duration of melatonin as an antidepressant in a rat model of depression. The rats were subjected to a six-week period of unpredictable mild stress followed by melatonin treatment. Three groups of rats were included in this study: Controls (CON - no stress exposure), Chronic Unpredictable Mild Stress (CUS) and CUS followed by melatonin (MT). Stressors consisted of exposure to rotation on a shaker, placement in a chamber maintained at 4°C, lights off for 3h, lights on overnight, exposure to an aversive odor, 45° tilted cages, food and water deprivation and crowding and isolated housing. Subsequently, the saline vehicle (CUS) or melatonin was administered at a dose of 10mg/kg for 14days period. Body weight and behavioral tests were used to evaluate depression-like behavior and its recovery following melatonin treatment. While body weight increases were significantly lower in rats exposed to CUS versus CON, body weights of the MT group increased significantly following melatonin treatment as compared with the CUS group. With regard to results obtained with behavioral assays indicative of depression, rapid and long-term functional recoveries in depression were observed in the MT as compared to the CUS group. The results indicate that not only does melatonin induce an antidepressant-like action within this rat model of depression, but does so with a rapid onset and prolonged efficacy. As most current treatments for depression require an extended period of administration, our current results suggest that melatonin may prove to be a particularly effect agent to promote a rapid onset and prolonged behavioral benefits in the treatment of depression.