Background:: Nickel ions (Ni2+) is a heavy metal with wide industrial uses. Environmental and occupational exposures to Ni are potential risk factors for brain dysfunction and behavioral and neurological symptoms in humans. Method: We reviewed the current evidence about neurochemical and behavioral alterations associated to Ni exposure in laboratory animals and humans. Results: Ni2+ exposure can alter (both inhibition and stimulation) of dopamine release and inhibit glutamate NMDA receptors. Few reports claim an effect of Ni2+ at the level of GBA and serotonin neurotransmission. At behavioral levels, exposure to Ni2+ in rodents alters motor activity, learning and memory as well anxiety and depressive-like symptoms. However, no analysis of dose-dependent relationship has been studied regarding these effects and the levels of the Ni2+ in brain, in blood or urine. Conclusion: Further research is needed to correlate the concentration of Ni2+ in biological fluids with specific symptoms/deficits. Future studies addressing the impact of Ni2+ under environmental or occupational exposure should use administration protocols leading to Ni2+ levels similar found in general population or occupationally exposed workers.

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