Abstract

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.

Highlights

  • Cd is one of the most toxic elements that bio-accumulates in the environment [1], especially in industrial areas via atmospheric dispersion and ground contamination surrounding metal emitting industries [2]

  • In the Morris Water Maze test, the space learning and spatial memory were significantly impaired in the group Cd-1

  • Time spent in the central area (TCA) (Figure 1(a)): The results summarized in Figure 1 show that the treatment factor significantly affected the TCA (F(3.32) = 29.22, p < 0.001)

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Summary

Introduction

Cd is one of the most toxic elements that bio-accumulates in the environment [1], especially in industrial areas via atmospheric dispersion and ground contamination surrounding metal emitting industries [2]. At peripheral level, prolonged exposure to Cd will cause toxic effect due to its accumulation over time in a variety of tissues, including kidneys, liver, central nervous system (CNS), and peripheral neuronal systems [4]. Behavioral alterations following heavy metal exposure have been related to hippocampal dysfunction [11]. In this direction, animal studies involving Cd exposure exhibit behavioral alterations. Rats exposed to Cd had decreased memory, as well as altered anxiety and fear responses [12] These behavioral deficits correlated with levels of oxidative stress markers in the hippocampus of these rats [12]. Our hypothesis is that behavioral dysfunction (depression-like, anxiety-like and memory deficit) provoked after chronic administration of Cd, might be linked to an increase in oxidative stress

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