Role of voltage-dependent calcium channels on the striatal in vivo dopamine release induced by the organophosphorus pesticide glyphosate.

In the present study, we investigated the role of voltage-sensitive calcium channels (VSCCs) on the striatal dopamine release induced by the pesticide glyphosate (GLY) using selective VSCC inhibitors. The dopamine levels were measured by in vivo cerebral microdialysis coupled to HPLC-ED. Nicardipine (L-type VSCC antagonist) or ω-conotoxin MVIIC (non-selective P/Q-type antagonist) had no effect on dopamine release induced by 5 mM GLY. In contrast, flunarizine (T-type antagonist) or ω-conotoxin GVIA (neuronal N-type antagonist) significantly reduced GLY-stimulated dopamine release. These results suggest that GLY-induced dopamine release depends on extracellular calcium and its influx through the T- and N-type VSCCs. These findings were corroborated by molecular docking, which allowed us to establish a correlation between the effect of GLY on blocked VSCC with the observed dopamine release. We propose new molecular targets of GLY in the dorsal striatum, which could have important implications for the assessment of pesticide risks in non-target organisms.

Role of voltage-gated calcium channels on striatal dopamine release induced by inorganic mercury in freely moving rats.

The possible role of voltage-sensitive calcium channels (VSCC) activation on the HgCl2-induced dopamine release was investigated using selective VSCC blockers and the dopamine levels were measured by HPLC from samples obtained by in vivo brain microdialysis. Infusion of HgCl2 in nicardipine (10 or 100 µM) or flunaricine (10 µM) pretreated animals had no significant effect on dopamine release induced by HgCl2. Pretreatment with 100 µM flunaricine, 20 µM ω-conotoxin MVIIC, or ω-conotoxin GVIA significantly decreased the HgCl2-induced dopamine release over 61%, 88%, and 99%, respectively. HgCl2-induced dopamine release could be produced, at least in part, by activation of VSCC at dopaminergic terminals, especially N- and P/Q-type.

Role of ionotropic glutamatergic receptors and nitric oxide in the effects of flutriafol, a triazole fungicide, on the in vivo striatal dopamine release.

Flutriafol is a triazole fungicide that induces spontaneous and depolarization-stimulated release of dopamine from rat striatum, although the neurochemical mechanism by which this fungicide induces this effect is unknown. The purpose of the present work was to assess the implication of ionotropic glutamatergic receptors and nitric oxide (NO) production in the flutriafol-induced dopamine release from rat striatum. To this, we have used non-competitive antagonists of NMDA (dizocilpine, MK-801), and (AMPA)/kainate (6-cyano-7-nitroquinoxaline-2,3-dione, CNQX) receptors, or nitric oxide synthase (NOS) inhibitors (Nomega-nitro-L-arginine -L-NARG - and 7-nitro-indazol - 7-NI), to study the striatal dopamine release induced by flutriafol. Intrastriatal infusion of 6 mM flutriafol increased the dopamine levels to 984 ± 141%, with respect to basal levels. Infusion of flutriafol (6 mM) in MK-801 (500 µM) or CNQX (500 µM) pretreated animals, increased striatal dopamine levels to 489 ± 74% and 477 ± 78%, with respect to basal levels, respectively, these increases being 50.3% and 51.5% smaller than those induced by flutriafol in non-pretreated animals. Infusion of flutriafol (6 mM) in L-NARG (1 mM) or 7-NI (100 µM) pretreated animals, increased the extracellular dopamine levels to 400 ± 88.5 and 479 ± 69.4%, with respect to basal levels, respectively, these increases being 59.3 and 51% smaller than those induced by flutriafol in non-pretreated animals. In summary, flutriafol appears to act, at least in part, through an overstimulation of NMDA receptors with possible NO production to induce dopamine release, and the administration of NMDA and AMPA/kainate receptor antagonists and NOS inhibitors protects against flutriafol-induced dopamine release from rat striatum.