Protection from inorganic mercury effects on the in vivo dopamine release by ionotropic glutamate receptor antagonists and nitric oxide synthase inhibitors

The possible role of ionotropics glutamate receptors on the HgCl2-induced dopamine (DA) release from rat striatum was investigated by using in vivo brain microdialysis technique after administration of selective NMDA and AMPA/Kainate receptors antagonists dizocilpine (MK-801), D (−)-2-amino-5-phoshonopentanoic acid (AP5), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Moreover, we have also studied the effects of nitric oxide synthase (NOS) inhibitors l-nitro-arginine methyl ester (l-NAME) and 7-nitro-indazol (7-NI) on HgCl2-induced DA release. Intraestriatal infusion of 1 mM HgCl2 increased striatal DA to 1717.2 ± 375.4% respect to basal levels. Infusion of 1 mM HgCl2 in 400 μM MK-801 pre-treated animals produced an increase on striatal DA levels 61% smaller than that induced in non-pre-treated animals. In the case of AP5, this treatment reduced 92% the increase produced by HgCl2 as compared to non-pre-treated rats. Nevertheless, the administration of CNQX did not produce any effect on HgCl2-induced dopamine release. Intrastriatal infusion of 1 mM HgCl2 in 100 μM l-NAME pre-treated animals produced an increase on extracellular DA levels 82% smaller than produced by HgCl2 alone. In addition, the pre-treatment with 7-NI reduced 90% the increase produced by infusion of HgCl2 alone in rats. Thus, HgCl2-induced DA release could be produced at last in part, by overstimulation of NMDA receptors with NO production, since administration of NMDA receptor antagonists and NOS inhibitors protected against HgCl2 effects on DA release.