Synthesis and Influence of Two Quinoxalinone Derivatives on Anxiety- and Depressive-Like Responses in Wistar Rat

Two new quinoxalinone derivatives have been synthesized adopting the HONG method, and investigated for some neuropharmacological effects (anxiety- and depressive-like responses) in rats. The present experiment sought to determine whether treatment with these compounds produces changes in affective responses. We found that the chronic injection of 6-nitro-2(1H)-quinoxalinone (NQu) showed obvious anxiolytic- and antidepressant-like effects, respectively, measured in the behavioral tests of Elevated Plus Maze (EPM) and Forced Swim Test (FST). At the dose of 30 mg/kg, NQu showed a comparative anxiolytic-like effect in rats as diazepam (Dz) (1 mg/kg), and a comparative antidepressant effect as clomipramine (Clmp) (2 mg/kg;i.p). The 2(1H)-quinoxalinone (Qu) significantly reduced depressive-like responses as evaluated in FST, whereas no anxiolytic-like effect was found as measured by open field test (OF). Additionally, the locomotor activity levels were unaffected by treatment as measured by OF and EPM.

Affective Responses of Early Life Photoperiod in Male Wistar Rats

Behavior changes season dependant are probably linked to change in day length or photoperiod. Although much research on seasonality in small mammals has focused on photoperiod manipulations in adults, early life photoperiod is also an important source of seasonal information and can establish individual’s developmental trajectory by regulating somatic and reproductive development and affective responses to day lengths later in life. The experiments developed in this work are based on the hypothesis that early life photoperiod affect emotionality in adult rats. To cheek this hypothesis, male rats were exposed at birth to different photoperiods (LP: 16L/8D;SP: 8L/16D). 8, 16 or 24 weeks later, rats were subjected to different behavioral tests to quantify anxiety-like behavior. Independently of duration, rats exposed to SP exhibited higher levels of anxious-like behavior than rats raised in LP, in an open field test (OFT) and in elevated plus maze (EPM). Repeated comparisons showed that photoperiod effect was accentuated after 16 weeks of treatment. 24 weeks of treatment failed to induce any effect on emotionality in male rats. Our results indicate that changes in day length are associated with different levels of anxious-like behaviors;consistent with the conjecture that early life photoperiod may influence affective behavior in adult male rats.

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.

Does Argan Oil Supplementation Affect Metabolic Parameters and Behavior in Wistar Rats?

Argan oil is renowned for its particular biochemical profile: high-fat oleic and linoleic acids, tocopherols, sterols, polyphenols. This composition gives it nutritional, therapeutic and preventive properties against dermatological, metabolic and proliferative diseases. The composition of argan oil assigns its benefits to mental health;it would be provided with possible effects on the prevention and/or cure of stress related disorder. This work aims to evaluate the impact of argan oil dietary on the behavioral response, biochemical and hematological constants and histological profiles of adrenal involved in emotional responses to stress. The variation of these parameters was evaluated in Wistar rats receiving dietary 10 ml/Kg/day of argan oil, starting from weaning, for 13 weeks. Our results show that supplementation has resulted in an increase in locomotor activity, reduced sensitivity to frightening environments with sex dependent variation. Moreover, lipid markers, corticosterone and lymphocytes show a rising trend. If the important role of argan oil diet in cardio-metabolic health is generally well recognized;for mental health, it is the first study that needs further investigation linking between the nervous system, inflammation parameters and metabolism.

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.

Evaluation of Acute Toxicity and Sedative Effects of Ethylic Extract of <i>Thymelaea lythroides</i>in Wistar Rats

The purpose of this study was to evaluate the acute toxicity and sedative effect of the ethylic extract of Thymelaea lythroides (Tl) on Wistar rats. The study was based on the gavage administration of the ethylic extract of Tl with different doses (i.e. 200, 400, 500 and 5000 mg/kg), where the toxicity and the sedative activity of the plant were observed and the obtained results were analyzed using the ANOVA test followed by the Bonferroni test. The main results of this study showed that the lethal dose of the ethylic extract of Tl was higher than the 5000 mg/kg dose. Moreover, when compared to the control rats, the animals treated with 5000 mg/kg of the extract exhibited significant reduction in appetite for food and water in the first week. Furthermore, results of the psychotropic test conducted during this study showed visible effects on the exploratory activity of the rats. The dose of 5000 mg/kg was also found to have a significant central nervous system effect;the locomotor activities of the animals decreased in a manner similar to those administered with Zepam as control.

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.

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.

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.

Methyl Donors Supplementation Attenuates the Adverse Effects of Maternal High Fructose Diet of Offspring Emotional and Cognitive Behaviors

Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles’ progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.