4.6 Article

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

Journal

ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
Volume 104, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.etap.2023.104285

Keywords

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

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This study investigated the role of voltage-sensitive calcium channels (VSCCs) in the striatal dopamine release induced by the pesticide glyphosate (GLY). The results showed that GLY-induced dopamine release depends on the influx of extracellular calcium through T- and N-type VSCCs. These findings have important implications for assessing pesticide risks in non-target organisms.
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 ro-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 ro-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.

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