Abstract
Chronic stress can impair brain functions and play a well-known role in the development of stress-related disorders such as anxiety. Melatonin (Mel) is a neurohormone which regulate several physiological processes including mood and behavior. This experimental study was designed to evaluate the effect of Mel on chronic immobilization stress (CIS) for 6 weeks in rats and to elucidate its possible underlying mechanisms. Twenty-eight adult male Wistar albino rats were divided into four equal groups: the control group, the Mel-treated group which was injected daily with Mel (10 mg/kg/day; IP) for 6 weeks, the stressed group which was subjected to CIS protocol daily for 6 weeks, and the Mel-treated stressed group which was injected with Mel and concurrently exposed to CIS protocol for 6 weeks. The Mel-treated stressed group showed reduction of both relative adrenal weight and the serum corticosterone levels, suppression of the anxiety-like behavior, increased levels of serotonin, noradrenaline and oxytocin in the frontal cortex, and improved histopathological structure and decreased chromogranin A (CgA) protein expression in the frontal cortex when compared with the chronically stressed group. We concluded that Mel is anxiolytic and this effect was mediated in part by its ability to increase the central release of oxytocin and monoamines and to downregulate CgA protein expression in the frontal cortex.