The moderate increase in DA metabolism combined with the impairments of motor functions

locomotor activities measured during the 35 days of Mn intoxication revealed a progressive decrease in horizontal and stereotypic movements compared to control animals. The observed decrease in spontaneous locomotor activity in the open field is consistent with earlier observations. In addition, Betharia and Maher observed a decrease in locomotor activity in male rats pups, which were exposed to Mn during gestation and lactation. One possibility is that the locomotor activity may be influenced by the reduction of weight gain in Mn-intoxicated animals. However, it is unlikely that the decrease in locomotor activity can be due to reduced weight gain as it has been reported that undernourished as well as malnutrished rats, who showed the same profile of weight gain reduction, increased their locomotor activity in the open field. Moreover, we show that Mn intoxication significantly and gradually affected motor coordination expressed by the very short time spent on rotating bar in the rotarod test, in line with another study carried out in Mn-intoxicated mice. Our results clearly show a link between locomotor and motor coordination deficits and Mn intoxication suggesting that Mn affects the central structures involved in the control of motor behavior such as basal ganglia. From a behavioral point of view, motor disabilities induced by Mn are somehow similar to those observed in rat models of parkinsonism and also in rats submitted to the intoxication with lead, which is another heavy metal known for its neurotoxic effects. Motor coordination deficit can also be due, at least in part, to ataxia. Indeed, excess accumulation of Mn due to impaired transport or failure of hepatic detoxification mechanisms may result in ataxia implicating the cerebellum in addition to basal ganglia. Interestingly, Mn-induced motor deficits are not related to DAergic depletion comparable to that reported in Parkinson’s disease or in animal models of the disease. Indeed, Mn intoxication increased the striatal tissue level of dopamine and its principal metabolite DOPAC. Contrasting data have been reported concerning the impact of Mn on the DAergic system, depending on the route of administration and the dosage used. Our results are in line with those of Ingersoll et al. who reported that Mn in the drinking water significantly increased the level of dopamine and DOPAC in the striatum. However, it has been shown that DA contents were decreased after intrathecal administration or inhalation of Mn. Interestingly, it has been shown that at lower doses, Mn increased DA and its metabolite levels, while the opposite effect was seen at higher doses. The dose used in our study is considered as a low dose. Thus, it is possible that the increase in tissue levels of DA and DOPAC may reflect a local action of Mn, which may precede a dysfunction of DAergic neurons. Although we do have direct evidence for an alteration of the DAergic tone in the striatum.

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