Mercury is a neurotoxin that exists in a number of physical and chemical forms, producing different effects in the brain. Methylmercury (MeHg) produces significant increases in the spontaneous output of dopamine (DA) from rat striatal tissue (Faro et al. 2000). Because the organic (MeHg) and inorganic (HgCl, HgCl₂) forms of mercury are neurotoxic to different degrees, in this work some standard pharmacological agents to determine the neurochemical basis for HgCl₂-induced DA release were used.

All animals were humanely killed. Animals were anaesthetized I.P. with choral hydrate (400 mg kg^-1) and a microdialysis probe was stereotaxically implanted in the striatum. The day after surgery, a Ringer solution (147 mM NaCl, 4 mM KCl, 3.4 mM CaCl₂ pH 7.4) was pumped through the microdialysis probe at a flow rate of 2 µl min^-1. Dialysates were collected every 15 min, and after three basal samples 1 mM HgCl₂ was infused during 60 min. The perfusate was then switched back to the unmodified perfusion medium and the infusion was carried out for an additional period of 120 min. In order to determine the possible mechanisms of dopamine release induced by HgCl₂, we analysed the in vivo DA release following the administration of nomifensine (NOM), and reserpine (RES) together with HgCl₂. Dopamine striatal levels were analysed by HPLC with electrochemical detection (Duran et al. 1998). The results are shown as the means ± S.E.M. of 5-6 experiments expressed as a percentage with respect to basal levels. Statistical analysis of the results was performed by means of repeated measures ANOVA and the Student-Newman-Keuls multiple range test. The experiments were performed according to the guidelines of the European Union Council (86/609/EU) for the use of laboratory animals.

HgCl₂ induced an increase of striatal DA levels to 1835 ± 410 % of basal values. Co-infusion of HgCl₂ and NOM (50 µM) produced increases in the release of DA (4824 ± 1038 %) (n = 5, P < 0.01) higher than those produced by NOM alone (2870 ± 319 %) (n = 5, P < 0.01). Three hours after I.P. reserpine injection (15 mg kg^-1), extracellular DA levels decreased to 17.2 ± 7.0 % of basal levels. Infusion of HgCl₂ in RES-pretreated animals increased striatal DA levels to 197 ± 45 % (n = 5, P < 0.001) of reserpinized levels, this effect of HgCl₂ on striatal DA levels being significantly lower than that observed in non-reserpinized animals. The effect on the extracellular DA levels in the group treated with HgCl₂ and NOM seems to be additive compared with those induced by HgCl₂ or NOM alone. This could indicate that HgCl₂ acts in a different way from NOM in order to increase the striatal DA levels. Because NOM increases DA extracellular levels acting on the DA transporter (DAT), our results could indicate that HgCl₂ induced an increase in DA striatal levels by means of exocytotic vesicular release. This seems to be confirmed by the results obtained in the group of RES-pretreated animals, in which the HgCl₂-induced DA release is avoided by the depletion of vesicular DA produced by reserpine. This mechanism of action of HgCl₂ on striatal DA release is different from that previously found for the MeHg, which seems to act by a mechanism mediated by DAT (Faro et al. 2002).

This study was supported by grants from the MCyT (Spain) in conjunction with FEDER (BQU2002-00083) and the Conselleria de Educacion e Ordenación Universitaria da Xunta a de Galicia (PGIDT02PXIB30101PR).