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.

Effect of Chronic Aluminum Administration on Affective and Cognitive Behavior in Male and Female Rats

In this study, we investigated the effect of chronic exposure of low doses of Aluminum on affective and cognitive disorders in male and female rats. Twenty-five rats for each gender are used and the treatment carried out for 8 weeks. Animals received distilled water for control or an intraperitoneal injection of different doses of Aluminum: 0.125, 0.25, 0.5 and 1 mg/kg. Behavioral performance is measured in various tests mainly the Open Field, Elevated Plus Maze, Force Swimming Test, Morris Water Maze, Y-maze and Object Recognition Test. Al exerts anxiogenic properties and depressive effect. The effect begins at 0.25 mg/kg to reach a maximum at 1 mg/kg. In addition, chronic exposure to Aluminum causes cognitive disorders characterized by affection of memory and influence spatial learning performance. The effect of Aluminum on working memory is effective just at 1 mg/kg, while the effect on spatial learning performance begins at 0.25 mg/kg to reach a maximum at 1 mg/kg. In conclusion, Aluminum enhances anxiety and depression parameters and cognitive disorders characterized by the affection of memory and spatial learning performance.

Effect of Chronic Administration of Cadmium on Anxiety-Like, Depression-Like and Memory Deficits in Male and Female Rats: Possible Involvement of Oxidative Stress Mechanism

The main objective of this work is to study the effect of chronic administration of cadmium (Cd) on the level of depression-like, anxiety-like, memory state and oxidative stress in male and female Wistar rats. For this purpose, this study was conducted with 24 rats for each gender. Four groups were constituted: (Group 1: Control): received saline solution NaCl (0.9%), (Group 2: Cd-0.25;Group 3: Cd-0.5;Group 4: Cd-1): received daily 0.25 mg/kg, 0.5 mg/kg and 1 mg/kg of Cd respectively during 8 weeks. After treatment period, animals were tested in the open-field, elevated plus maze tests for anxiety-like behavior, and forced swimming test for depression-like behavior. The Y maze was used to evaluate the working memory and the Morris Water Maze, to evaluate space learning and spatial memory. The results revealed that in males, all doses of Cd provoke depression-like, while in females only the group treated with 1 mg/kg Cd shows elevated depression-like behavior. In regard to anxiety-like behavior, Cd induces an anxiogenic effect in both genders tests. In the Y-Maze test, both males and females expressed a low percentage of alternations, suggesting that working memory was affected by Cd at 1 mg/kg. In the Morris Water Maze test, the space learning and spatial memory were significantly impaired in the group Cd-1. Neurochemical analysis showed that levels of nitric oxide and lipid peroxidation in the hippocampus were significantly increased after Cd treatments. Overall analysis of our data revealed that Cd caused significant alterations in the examined parameters that were sex-dependent and dose-dependent.

Impact of the Association of a High Fructose Diet and Chronic Mild Stress on Metabolic and Affective Disorders in Male Rat

An early unbalanced nutritional diet can induce affective disorders in adulthood. As well as stress in adolescence can accentuate these disorders. Both human and rat structural changes have been demonstrated in the hippocampus, likewise, oxidative stress may be involved in these disturbances. The objective of this study is to see the impact of a high-fructose diet (PN21) associated with chronic mild stress (CMS) at the end of adolescence (PN55) on metabolic and affective disorders in rats Wistar. This study was performed on four groups of male rats: control group, CMS for five weeks (PN55), fructose for ten weeks (PN21) and fructose for ten weeks (PN21) associated with CMS for five weeks (PN55). These animals underwent behavioral tests to evaluate their affective states (open field test, Sucrose preference test). After sacrifice, the dosage of glucose, triglycerides and total cholesterol was performed at the prefrontal cortex (CPF) and also at the hippocampus;the dosage of nitric oxide (NO) was performed, too. The bulk of our results show that fructose induces metabolic disturbances;the CMS induces a state of depression-like, while the association potentiated metabolic disturbances, depression-like state and also inducing anxiety. This study has shown that fructose and CMS can disrupt the various functions of the body and their association can potentiate these disturbances.

Modulation of Anxiolytic-Like and Antidepressant-Like Effects of Melatonin by Imipramine in Wistar Rats: Possible Interaction with Central Monoaminergic Systems

Our current study aims to explore the interaction of melatonin (MEL) with the monoaminergic system on the pathophysiology of affective disorders in Wistar rats. We mention here that, the role of monoaminergic transmission in the pathophysiology of affective disorders in humans is demonstrated in most recent reports. In this sense, our current work aims to explore the effect of melatonin (MEL) with or without imipramine (IMP) on levels of depression and anxiety in Wistar rats and would determine the role of MEL in modulating serotonin, noradrenaline and dopamine neurotransmission. From this point, twenty-four female Wister rats were divided into 4 groups of 6 animals and received subcutaneously during 4 weeks different doses of MEL (4 mg/kg), IMP (2 mg/kg) or MEL (4 mg/kg) + IMP (2 mg/kg). Behavioral performance especially anxiety and depression is measured in the open field (OFT), elevated plus maze (EPM) and forced swim test (FST). The anxiety-like and antidepressant-like effects were observed with MEL at 4 mg/Kg and IMP at 2 mg/Kg but the potentiating effect was more observed with the two combined molecules (MEL and IMP), since locomotors activity assessed by the OFT and EPM was not affected. These effects suggest that psychopharmacological actions of MEL are due, at least in part, to its ability to potentiate the central monoaminergic transmitter effects.

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.

Melatonin and Diazepam Affect Anxiety-Like and Depression-Like Behavior in Wistar Rats: Possible Interaction with Central GABA Neurotransmission

Recent studies have shown the importance of the GABA-ergic transmission in the pathophysiology of anxiety and depressive disorders in humans. Our present study aims to investigate the interaction of melatonin (MEL) with this system by exploring the effects of MEL with or without a facilitator of GABA-ergic neurotransmission, diazepam (DZ) on the levels of depression and anxiety in Wistar rats. For this purpose, different doses of MEL (2, 4 or 16 mg/kg) or DZ (2 mg/kg) are subchronically administered during 15 days. After pharmacological treatments, anxiety levels are evaluated in behavioral tests of Open Field (OFT) and elevated plus maze (EPM) and depression levels are evaluated by the forced swim test (FST). The results showed that MEL produces anxiolytic-like and antidepressant-like effects in a dose-dependent manner;the maximum effect was obtained at a dose of 16 mg/kg. However, a dose of 4 mg/kg is necessary to induce an effect. The effect of MEL and DZ reported in this study concerns selective modulation of behavioral anxiety and depression since locomotor activity assessed by the OFT and EPM was not affected. The subchronic injection of MEL at 4 mg/kg, DZ at 2 mg/kg or the two combined molecules also induces also anxiety-like and antidepressant-like behavior. In addition, a potentiating effect between MEL and DZ was observed. These effects suggest that psychopharmacological actions of MEL are due, at least in part, to its ability to improve the central GABA-ergic transmission.

Conversion of L-Tryptophan into Melatonin Is the Possible Action Pathway Involved in the Effect of L-Tryptophan on Antidepressant-Related Behavior in Female Rats: Analysis of the Influence of Treatment Duration

The aim of this study was to determine the effect of pharmacological doses of melatonin (MEL) and L-tryptophan (L-TRP) on depression-like behavior in female rats submitted to the forced swimming test (FST) after 2, 4, 6 or 8 weeks of treatment. This will allow exploring the different mechanisms of L-TRP actions particularly that due to its conversion into MEL. For this purpose, four groups of 24 rats each were constituted;(Group 1: Control): received saline solution NaCl (0.9%), (Group 2: MEL4): received 4 mg/Kg of MEL, (Group 3: L-TRP4): received 4 mg/Kg of L-TRP and (Group 4: L-TRP20): received 20 mg/Kg of L-TRP. Animals of each group were distributed on 4 subgroups of 6 rats submitted to different time treatments. The duration of immobility (TIM) and struggling period (TST) of rats in FST were measured after 2, 4, 6 and 8 weeks of drug treatment and the effects of MEL and L-TRP were compared. Chronical administration of different doses of MEL or L-TRP failed to induce any anti-depressant activity in rats subjected to FST after 2 weeks of treatment. However, after 4 weeks, daily administration of MEL at 4 mg/Kg significantly reduced the immobility period and enhanced struggling time. After 6 weeks, MEL at 4 mg/Kg and L-TRP at 20 mg/Kg were both effective in reducing immobility and increasing struggling movement, their effects being statistically comparable. All treatments were able to significantly reduce immobility time and increase struggling duration after 8 weeks, but L-TRP at 4 mg/Kg was less potent than MEL and L-TRP at 20 g/Kg. The antidepressant-like activity of L-TRP was dose and time dependent, and that of MEL was time dependent. In conclusion, the study showed that at pharmacological doses, MEL and L-TRP have anti-depressant action, and such effect is dependent on time treatment;MEL?is more effective than L-TRP. In conclusion, L-TRP, through MEL, 5-HT or by itself could modulate aminergic neurotransmission in the different brain areas to ensure its behavioral effects.

Affective Behavior Dysregulation Was Induced by Chronic Administration of Copper in Wistar Rats

As both deficiency and excess of copper (Cu) can be harmful, dysregulation in its homeostasis has been connected with various neurological disorders. The present study was undertaken to examine whether Cu chronic administration can induce alterations of affective behavior especially anxiety and depression levels in male and female rats. Twenty-four rats, for each gender, divided in control and three test groups (n = 6), were injected intraperitoneally with saline (0.9% NaCl) or CuCl2 (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) for 8 weeks. After treatment period, animals were tested in the open-field, elevated plus maze tests for anxiety-like behavior, and forced swimming test for depression-like behavior. Results demonstrated that Cu administered chronically, exerts an anxiogenic effect in rats. In the OFT, Cu decreases the TCA and NRC parameters without modifying the locomotor activity represented by the NTS parameter. With regard to EPM, Cu decreases TOA and EOA parameters without modifying the TAE parameter. A significant increase in depression-like symptoms was also exhibited by Cu treated rats (p 2 showed maximum anxiety-like and depression-like symptoms as compared to controls as well as from the other two doses indicating dose-dependent effects of chronic Cu administration. Overall, these results suggest that intoxication with Cu has potentially deleterious effects on brain as reflected in behavioral dysfunctions such as depression and anxiety.