Mediation of a glutamate antagonist, a NOS inhibitor and antioxidants with – SH groups on striatal dopamine release induced by clothianidin

Abstract

Is Clothianidin is a neonicotinoid insecticide with selective action on nicotinic acetylcholine receptors. The aim of this study was to determine if the administration of a glutamate antagonist (APV), a NOS inhibitor (L-NAME) or two antioxidants (glutathione, and dithiothreitol,) prevent the increase in the striatal dopamine levels induced by clothianidin, using the microdialysis technique in freely moving and conscious rats. Intrastriatal administration of clothianidin (3.5 mM) produced an increase in striatal dopamine levels of 2462 ± 627%, with respect to basal levels. Coadministration of 0.65 mM APV and 3.5 mM clothianidin generated an increase in extracellular dopamine levels of 1089 ± 243.5%, being this increase 55.7% lower than the generated by clothianidin alone. Coadministration of 0.1 mM L-NAME and 3.5 mM clothianidin generated a significant increase in extracellular dopamine levels of 836.5 ± 150.6%., this increase is 70% lower than the generated by clothianidin alone. Coadministration of 3.5 mM clothianidin in combination with 0.4 mM glutathione induced an increase in striatal dopamine levels of 465.6 ± 126.8% , indicating that the administration of glutathione results in an inhibition of 81% of the effect generated by the infusion of clothianidin alone. Administration of 3.5 mM clothianidin associated with 0.005 mM dithiothreitol induced an increase in extracellular dopamine levels in the striatum of 693.8 ± 117.8% with respect to basal levels, being this increase 72% lower that the generated by clothianidin alone. Our results suggest that the effect of clothianidin on striatal dopamine release can be reduced by the administration of a glutamate antagonist, a NOS inhibitor or antioxidants with –SH groups, which suppose a simple protection mechanism against the damage caused for clothianidin.