Behavioral and biochemical effects of neonicotinoid thiamethoxam on the cholinergic system in rats.

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.

Evaluation of the effects and mechanisms of action of flutriafol, a triazole fungicide, on striatal dopamine release by using in vivo microdialysis in freely moving rats.

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.

Comparative effects of organic and inorganic mercury on in vivo dopamine release in freely moving rats.

The present study was carried out in order to compare the effects of administration of organic (methylmercury, MeHg) and inorganic (mercury chloride, HgCl 2 ) forms of mercury on in vivo dopamine (DA) release from rat striatum. Experiments were performed in conscious and freely moving female adult Sprague-Dawley (230-280 g) rats using brain microdialysis coupled to HPLC with electrochemical detection. Perfusion of different concentrations of MeHg or HgCl 2 (2 microL/min for 1 h, N = 5-7/group) into the striatum produced significant increases in the levels of DA. Infusion of 40 microM, 400 microM, or 4 mM MeHg increased DA levels to 907 +/- 31, 2324 +/- 156, and 9032 +/- 70% of basal levels, respectively. The same concentrations of HgCl 2 increased DA levels to 1240 +/- 66, 2500 +/- 424, and 2658 +/- 337% of basal levels, respectively. These increases were associated with significant decreases in levels of dihydroxyphenylacetic acid and homovallinic acid. Intrastriatal administration of MeHg induced a sharp concentration-dependent increase in DA levels with a peak 30 min after injection, whereas HgCl 2 induced a gradual, lower (for 4 mM) and delayed increase in DA levels (75 min after the beginning of perfusion). Comparing the neurochemical profile of the two mercury derivatives to induce increases in DA levels, we observed that the time-course of these increases induced by both mercurials was different and the effect produced by HgCl 2 was not concentration-dependent (the effect was the same for the concentrations of 400 microM and 4 mM HgCl 2 ). These results indicate that HgCl 2 produces increases in extracellular DA levels by a mechanism differing from that of MeHg.

Comparative effects of organic and inorganic mercury on in vivo dopamine release in freely moving rats

The present study was carried out in order to compare the effects of administration of organic (methylmercury, MeHg) and inorganic (mercury chloride, HgCl 2 ) forms of mercury on in vivo dopamine (DA) release from rat striatum. Experiments were performed in conscious and freely moving female adult Sprague-Dawley (230-280 g) rats using brain microdialysis coupled to HPLC with electrochemical detection. Perfusion of different concentrations of MeHg or HgCl 2 (2 muL/min for 1 h, N = 5-7/group) into the striatum produced significant increases in the levels of DA. Infusion of 40 muM, 400 muM, or 4 mM MeHg increased DA levels to 907 ± 31, 2324 ± 156, and 9032 ± 70 percent of basal levels, respectively. The same concentrations of HgCl 2 increased DA levels to 1240 ± 66, 2500 ± 424, and 2658 ± 337 percent of basal levels, respectively. These increases were associated with significant decreases in levels of dihydroxyphenylacetic acid and homovallinic acid. Intrastriatal administration of MeHg induced a sharp concentration-dependent increase in DA levels with a peak 30 min after injection, whereas HgCl 2 induced a gradual, lower (for 4 mM) and delayed increase in DA levels (75 min after the beginning of perfusion). Comparing the neurochemical profile of the two mercury derivatives to induce increases in DA levels, we observed that the time-course of these increases induced by both mercurials was different and the effect produced by HgCl 2 was not concentration-dependent (the effect was the same for the concentrations of 400 muM and 4 mM HgCl 2 ). These results indicate that HgCl 2 produces increases in extracellular DA levels by a mechanism differing from that of MeHg.