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Summary: Pregnant rats were exposed to ethanol (EtOH) and/or methyl mercury (MeHg) during fetal brain development. Nitrergic activity was quantified by densitometric measurement of formazan deposits in the hippocampus, cerebellum and striatum of two-month-old offspring following histochemical assay for NADPH-diaphorase (NADPH-d) activity. Compared to control subjects, an increase in nitrergic activity was found in the molecular layer of dentate gyrus and in the lacunosum molecular and stratum radiatum of CA1 (cornus amoni 1) in the EtOH+MeHg group, whereas a single administration of EtOH increased the activity in all striatal segments. The cerebellum seems to be less sensitive at this time-point to intoxication, and presented an increase only at the molecular layer of EtOH-exposed animals when compared to the MeHg and EtOH+MeHg groups (ANOVA, one-way followed by Tukey''s test, p<0.05 or p<0.01). Taken together, results suggest that developmental exposure to EtOH and MeHg, singularly or in combination, alters nitrergic activity in adult rat in different ways depending on the region and layer of the central nervous system (CNS), and that these alterations might be related to different local metabolic properties. [Copyright &y& Elsevier]

Abstract: Studies involving alcohol and its interactions with other neurotoxicants represent the focus of several works of research due to the fact that the use of alcohol can sometimes leads to serious health problems. Fetal exposure to alcohol and mercury has a high incidence in some regions of Brazil, where there are pregnant women who are alcoholics and live in mining areas. This work was conducted to examine the effects of combined exposure to ethanol (EtOH) and methylmercury (MeHg) in rats during the development of the central nervous system (CNS). Experimental behavioral animal models/tests were used in order to examine locomotion, anxiety, depression and memory. Pregnant rats received tap water or EtOH 22.5% w/v (6.5g/kg per day), by gavage) during pregnancy and breast-feeding. On the 15th day of pregnancy, some groups received 8mg/kg of MeHg (by gavage). The groups were as follows: control, EtOH, MeHg and EtOH+MeHg. The experimental results showed that the EtOH, MeHg and EtOH+MeHg groups reduced the percentage of frequency and time spent in the open arms entries of the elevated plus-maze (EPM) test, when compared to the control group. This result suggests an anxiogenic behavioral response. The MeHg group increased locomotor activity in the arena and the immobility time in the forced swimming test, suggestive of depression-like behavior. The EtOH+MeHg group showed greater reductions in the percentages of frequency and time spent in the open arms entries in the EPM test, suggesting a sedative-behavior since the frequency of enclosed arm entries was affected. In the inhibitory avoidance task, the EtOH+MeHg group reduced the latency of the step-down response onto the grid floor, suggesting a cognitive and behavior dysfunctions. Taken together, the results suggest that EtOH and/or MeHg intoxication during the developing CNS may be a risk for deficits related to locomotor impairment, anxiety, depression and neurocognitive functions. There is a possibility that EtOH may prevent some of the MeHg responses, but the precise mechanism of action involved in this process needs to be considered for future research. [Copyright &y& Elsevier]