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

Abstract

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.

Keywords: Cerebral microdialysis; Glyphosate; Molecular docking; Voltage-sensitive calcium channels; in vivo dopamine release.