Effects of successive intrastriatal methylmercury administrations on dopaminergic system

The present study was carried out in order to determine the effects of intrastriatal administration of different doses (40 PM, 400 muM, and 4 mM) 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 muM, and 4 mM, 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 4 mM MeHg, whereas nonsignificant changes in metabolite levels were observed with the doses of 40 and 400 muM MeHg. A second infusion of 4 mM MeHg 24 h 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. (C) 2003 Elsevier Science (USA). All rights reserved.