Intrahippocampal Effects of Nickel Injection on the Affective and Cognitive Response in Wistar Rat: Potential Role of Oxidative Stress Mohamed Yassine El Brouzi 1 & Mouloud Lamtai 1 & Oussama Zghari 1 & Sihame Ouakki 1 & Ibrahim Azizoun 1 & Aboubaker El Hessni 1 & Abdelhalem Mesfioui 1 & Ali Ouichou 1 Received: 31 August 2020 /Accepted: 21 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract The present study focused on affective and cognitive behaviors in male Wistar rats, following direct and unique exposure to nickel chloride (NiCl 2 ), as well as the possible involvement of oxidative stress. The rats were exposed to NiCl 2 (300 μM), by intracerebral administration of 2 μL of this metal at the right hippocampus, using the stereotaxic approach. Five days after the surgery, a battery of behavioral tests was performed, including the open-field test (OFT) and elevated plus maze test (EPM) to assess the state of anxiety-like behavior and forced swimming test (FST) for depressive-like behavior. Y-maze and Morris Water Maze (MWM) were used to evaluate working memory and spatial learning. Thereafter, oxidative stress markers of the hippo- campus were evaluated. The results confirm that NiCl 2 exerts anxiogenic effects in both anxiety tests and depressogenic effects in the FST. In addition, MWM and Y-maze data show that NiCl 2 causes memory and spatial learning disorders. The biochemical assay results showed that intrahippocampal injection of NiCl 2 increased the levels of nitric oxide and lipid peroxidation (p < 0.001), while the activities of catalase and superoxide dismutase were significantly decreased in the hippocampus (p < 0.01). Overall, these results suggest that NiCl 2 causes affective and cognitive disorders and oxidative stress in rats. Keywords Nickel . Anxiety . Depression . Memory . Hippocampus . Oxidative stress Introduction Depression, anxiety, and cognitive-related disorders are the most important group of mental disorders. They represent a pathological condition characterized by a complex biological structure of etiology, involving genetic, epigenetic, and envi- ronmental factors. Heavy metal pollution is a global problem because of the persistent and continuing accumulation in the environment [1, 2]. Chronic exposure to heavy metals could affect mental health [3–8]. Among these metals is nickel (Ni), a toxic tran- sition metal used in industry and found in air, water, and food. Human overexposure to Ni emanating from the increasing application of Ni compounds in modern technologies is a major public health problem [9–11]. It has been reported that Ni exposure causes harmful effects in living organisms, such as genotoxicity, teratogenicity, immunotoxicity, and carcino- genicity [12–14]. Among the major target organs for Ni toxicity is the central nervous system (CNS) [15]. Exposure to Ni causes various neurological symptoms [13]. Recent studies have shown that Ni administration alters affective and cognitive behaviors and induces oxidative stress (OS) [16–18] and neurodegeneration of rats’ brain [19]. Ni causes ultrastructural modifications in hippocampal neurons, a brain structure strongly implicated in the etiology of affective and cognitive disorders [20–22]. In addition, several studies have shown that exposure to Ni induces apoptosis of sensory and olfactory bulb neurons, as well as behavioral deficiencies and disrupts neurotransmitters, such as catecholamines, glutamate, dopamine, and serotonin [23–26]. The involvement of oxidative stress (OS) mechanisms has also been suggested in the Ni-induced neurotoxicity [13]. Ni induces cytotoxicity in vitro associated with increased produc- tion of reactive oxygen species (ROS) [15, 18]. The nervous system is particularly sensitive to OS and mitochondrial dys- function due to its energy requirement and lipid content [27]. * Mohamed Yassine El Brouzi mohamedyassine.elbrouzi@uit.ac.ma 1 Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofaïl University, Kénitra, Morocco https://doi.org/10.1007/s12011-020-02457-5 / Published online: 23 November 2020 Biological Trace Element Research (2021) 199:3382–3392