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Thiamethoxam is a neonicotinoid insecticide, a group of pesticides that acts selectively on insect nicotinic acetylcholine receptors (nAChRs), with only a little action on mammalian nAChRs. Nevertheless, the selectivity of neonicotinoids for the insect nAChRs may change when these substances are metabolized. Therefore, we aimed to determine the potential effects of thiamethoxam on mammalian brain, testing the performance in the open field and elevated plus-maze of rats exposed to this insecticide and, in order to establish the neurochemical endpoints, we measured the acetylcholinesterase activity in different brain regions (hippocampus, striatum and cortex) and the high-affinity choline uptake (HACU) in synaptosomes from rat hippocampus. Treated animals received thiamethoxam (25, 50 or 100mg/kg) for 7 consecutive days. The results showed that treatment with thiamethoxam induced an increase in the anxiety behavior at two doses (50 or 100mg/kg). Moreover, there was a significant decrease in both HACU and acetylcholinesterase activity. Our hypothesis is that thiamethoxam (or its metabolites) could be acting on the central rats nAChRs. This would produce an alteration on the cholinergic transmission, modulating the anxiety behavior, acetylcholinesterase levels and HACU.

The purpose of the present work was to assess the effects of flutriafol, a triazole fungicide, on in vivo dopamine (DA) release from rat striatum, using brain microdialysis coupled to high-performance liquid chromatography with electrochemical detection (HPLC-EC). Intrastriatal administration of flutriafol (1, 6 and 12 mM) produced significant concentration-dependent increases in DA levels to 218.5+/-51%, 1376+/-245% and 3093+/-345% compared with basal values, respectively. Those increases in DA levels could be due to an increased DA exocytotic release and/or a change in the activity of DA transporter (DAT). Thus, we investigated the effects of flutriafol (6mM) under Ca(++)- or Na(+)-free conditions, and after pretreatment with reserpine and TTX. When flutriafol was perfused in either Ca(++)- or Na(+)-free Ringer, the DA levels reduced 92% and 70%, respectively; perfusion of flutriafol in TTX-treated (10 microM) or reserpine-pretreated animals (10mg/kg), reduced the levels of DA to 73% and 86%, respectively. Co-infusion of flutriafol and nomifensine (20 microM) shows that the flutriafol-induced DA release did not involve the DAT. Our results suggest that flutriafol induces DA release via vesicular-, Ca(++)-, Na(+)- and TTX-dependent mechanism, being independent of DAT.

The aim of this research was to verify the incidence of endocrine dysfunction associated with mercury intoxication in the hypothalamus-pituitary reproductive system of normally cycling or castrated female rats and the possible protective action of estrogen replacement therapy. We found no differences in the frequency of estrus cycle stages (diestrus I, diestrus II, proestrus, and estrus) in normally cycling female rats during 54 days of daily oral administration of 0.004, 0.02, and 1 mg/kg MeHgCl. Conversely, the higher dose (1 mg/kg) induced a significant decrease in content of luteinizing hormone releasing hormone (LHRH) into the medial hypothalamus when administered daily during 3 days in ovariectomized rats. This effect was associated with increased levels of mercury found in the anterior pituitary gland and medial hypothalamus, rather than the anterior and posterior hypothalamus, striatum or cerebellum. A decrease in plasma levels of luteinizing hormone (LH) was also detected after administration of 7.5 mg/kg MeHgCl. These disturbances in LHRH and LH secretion induced by mercury were abolished or superimposed (respectively) by estrogenic replacement therapy (0.025 mg/kg 17beta estradiol cypionate, intramuscular). These effects were associated with a significant reduction in mercury content of the anterior pituitary gland and medial hypothalamus, suggesting a protective estrogenic effect.

The present study was carried out in order to determine the effects of intrastriatal administration of different doses (40 microM, 400 microM, and 4mM) of methylmercury (MeHg) on dopaminergic system of rat striatum. Experiments were performed in conscious and freely moving rats using brain microdialysis coupled with liquid chromatography. Intrastriatal administration of MeHg produced significant increases in dopamine (DA) striatal levels (907+/-7%, 1870+/-319%, and 7971+/-534% for the doses of 40, 400 microM, and 4mM, with respect to basal). The increase in DA levels was associated with significant decreases in extracellular levels of its main metabolites dihydroxyphenylacetic acid (DOPAC) and homovallinic acid (HVA) (65.0+/-3.0% and 52.2+/-1.3%, respectively) using the dose of 4mM MeHg, whereas nonsignificant changes in metabolite levels were observed with the doses of 40 and 400 microM MeHg. A second infusion of 4mM MeHg 24h after first infusion also produced a rise of DA levels, but this increase was very small as compared with that produced by first infusion (7971+/-534% versus 985+/-186%). This second infusion of 4mM MeHg also decreased DOPAC and HVA levels, but this decrease was not significant as compared with that observed after first infusion (65.0+/-3.0% and 52.2+/-1.3% versus 62.4+/-5.2% and 63.4+/-7.4%, respectively). We discuss these effects based on a stimulated DA release and/or a decreased DA intraneuronal degradation.

In the present study, the effects of intrastriatal administration of different concentrations (40 microM, 400 microM, and 4 mM) of inorganic mercury (HgCl(2)) on the dopaminergic system of rat striatum were evaluated, using a microdialysis technique coupled to liquid chromatography-electrochemical detection. In previous studies, we discussed the effects of organic mercury (MeHg) administration on the striatal dopaminergic system on the basis of changes in the release and metabolism of striatal dopamine (DA). In the present study it is demonstrated that intrastriatal administration of all concentrations of HgCl(2) produced significant increases in the output of DA (1240, 2500, and 2658% for the concentrations of 40 microM, 400 microM, and 4 mM HgCl(2), respectively) from rat striatal tissue, associated with significant decreases in striatal levels of its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) with the concentrations of 400 microM and 4 mM HgCl(2) (74.4 and 3.4% for DOPAC and 71.0 and 50.6% for HVA, respectively), whereas no changes in metabolite levels were observed with the concentration of 40 microM HgCl(2). These effects are explained as a result of stimulated DA release and/or changed DA metabolism. The effects of intrastriatal administration of HgCl(2) were compared with those of MeHg on DA extracellular levels., (Copyright 2001 Academic Press.)

Mercury is a neurotoxic agent that produces different effects on the brain. In the present work, the effects of chronic doses of methyl mercury (MeHg) were studied on the dopaminergic system of the rat striatum, using microdialysis coupled to high-performance liquid chromatography in order to quantify the in vivo release of dopamine (DA) and its acidic metabolites DOPAC and HVA. The administration of an equivalent total dose of 6 mg/kg of MeHg induced significant increases in the striatal release of DA and/or its acidic metabolites, independently of the pattern of administration. These effects are discussed on the base of the release and the metabolization of DA. In conclusion, the effect of MeHg administered under these experimental conditions on the in vivo release of DA and its metabolites seems to have a dose-dependent component and seems to be an accumulative process., (Copyright 1997 Academic Press.)