The main objective of this study was to analyze the effects of sex, ovariectomy (Ovx) and orchidectomy (Orx) on antidepressant and anxiolytic effect of melatonin in forced swimming test, open field test and elevated plus maze test. Initially, 4 mg/kg of melatonin was daily administered, at 4:00 pm, to intact male and female rats during 8 weeks. Our results have shown that the effect of chronic injection of Mel is sex dependent in the three behaviors tests. Females rats have responded better than males in behavior test study after administration of melatonin, this difference between the sexes may be related to the action of sex hormones (androgens and estrogens) on behavior in males as well as in females. Secondly, to determine the possible interaction between Melatonin and steroid hormones, Ovx/sham female received Mel at dose of 4mg/kg alone or NaCl (0.9%) alone, and Orx/sham male received Mel at dose of 4 mg/kg alone or NaCl (0.9%) alone daily and during 8 weeks of treatment at 4:00 pm. All animals were tested in the open-field test, elevated plus maze test for anxiety behavior study, and forced swimming test for depression behavior study. Results revealed that Mel exerts an anxiolytic and antidepressant effects in the orchidectomized males and in intact females, confirming that the suppression of androgens by orchidectomy improved anxiolytic and antidepressant effects of melatonin in males. However in females, the suppression of estrogen by ovariectomy masked the antidepressant and anxiolytic effects of melatonin. Our results confirmed that the antidepressant and anxiolytic effects of melatonin are linked to sex hormones.
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