Chronic exposure to low levels of inorganic arsenic causes alterations in locomotor activity and in the expression of dopaminergic and antioxidant systems in the albino rat

Several studies have associated chronic arsenicism with decreases in IQ and sensory and motor alterations in humans. Likewise, studies of rodents exposed to inorganic arsenic (iAs) have found changes in locomotor activity, brain neurochemistry, behavioral tasks, oxidative stress, and in sensory and motor nerves. In the current study, male Sprague-Dawley rats were exposed to environmentally relevant doses of iAs (0.05, 0.5mg iAs/L) and to a high dose (50mg iAs/L) in drinking water for one year. Hypoactivity and increases in the striatal dopamine content were found in the group treated with 50mg iAs/L. Exposure to 0.5 and 50mg iAs/L increased the total brain content of As. Furthermore, iAs exposure produced a dose-dependent up-regulation of mRNA for Mn-SOD and Trx-1 and a down-regulation of DAR-D2 mRNA levels in the nucleus accumbens. DAR-D1 and Nrf2 mRNA expression were down-regulated in nucleus accumbens in the group exposed to 50mg iAs/L. Trx-1 mRNA levels were up-regulated in the cortex in an iAs dose-dependent manner, while DAR-D1 mRNA expression was increased in striatum in the 0.5mg iAs/L group. These results show that chronic exposure to low levels of arsenic causes subtle but region-specific changes in the nervous system, especially in antioxidant systems and dopaminergic elements. These changes became behaviorally evident only in the group exposed to 50mg iAs/L. © 2010 Elsevier Inc.

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