The Influence of Gonadectomy on Anxiolytic and Antidepressant Effects of Melatonin in Male and Female Wistar Rats: A Possible Implication of Sex Hormones

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.

Pinealectomy and Exogenous Melatonin Regulate Anxiety-Like and Depressive-Like Behaviors in Male and Female Wistar Rats

The main objective of this work was to 1) study the influence of endogenous melatonin (Mel) abolishment via pinealectomy and 2) explore exogenous Mel effect on anxiety-like and depressive-like behavior in male and female rats. Rats were shamoperated (Sh) or pinealectomized (Px) and following subgroups were selected 1) Px/NaCl (0.9%) and Sh/NaCl (0.9%) : rats injected subcutaneously, once daily for 8 weeks, with saline solution NaCl (0.9%) as vehicle;2) Px/Mel (4 mg/Kg) and Sh/Mel (4 mg/Kg): Rats similarly injected with 4 mg/Kg of Mel. All animals were housed under a photoperiod of (LD:16/8). After different treatments animals were tested in the open-field test (OFT), elevated plus maze test (EPM) to determine anxiety-like behavior, and forced swimming test (FST) to evaluate depressive-like level. Our results revealed that level of anxiety-like and depressive-like behavior are significantly higher in Px/NaCl (0.9%) when compared to Sh/NaCl (0.9%) group, suggesting that pinelectomy induced an anxiogenic and depressant effects. The Px effects would be due to the absence of endogenous Mel synthesis and release. Additionally, we clearly demonstrated that the level of anxiety-like and depressive-like behavior are higher in Px/Mel (4 mg/Kg) and Sh/Mel when compared respectively to Px/NaCl (4 mg/Kg) and Sh/NaCl groups suggesting an anxiolytic and antidepressant effects of exogenous Mel. Behavioral responses were sex dependent since the difference between females and males, especially, after melatonin administration, were statistically significant. These experiments provide evidence that pinealectomy and Mel regulated emotionally behavior in male and female rats.