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

espanolLa clotianidina es un insecticida neonicotinoide con actividad selectiva sobre los receptores de acetilcolina. El objetivo de este estudio es comprobar si un inhibidor de los receptores glutamatergicvos (APV), un inhibidor de la oxido nitrico sintetasa (L-NAME) y dos antioxidantes como el glutation y el dithiotreitol previene la liberacion de dopamina inducida por la clotianidina, usando la tecnica de microdialisis en ratas conscientes y en libre movimiento. La administracion intraestriatal de clothianidina (3.5 mM) produce un aumento de 2462 ± 627%, de los niveles estriatales de dopamina respecto a los niveles basales. La coadministracion de 0.65 mM de APV y 3.5 mM d clothianidina genera un a aumento de 1089 ± 243.5% de los niveles estriatales de dopamina, siendo este incremento 55.7% mas bajo que el generado por la clotianidina sola. La Coadministration de.0,1 mM de L-NAME y3.5 mM de clotianidina genera un aumento de 836.5 ± 150.6% de los niveles extracelulares de dopamina, siendo este aumento un 55.7% mas bajo que el generado por la clotianidina sola. La coadministracion of 3.5 mM clothianidina en combinacion con 0.4 mM de glutation induce un aumento de 465.6 ± 126.8% de los niveles estriatales de dopamina, indicando que la administracion de glutation provoca una inhibicion del 81% del efecto generado por la infusion de clotianidina sola. La administracion de 3.5 mM de clothianidina junto con 0.005 mM de diithiothreitol induce un aumento de 693.8 ± 117.8% en los niveles extracelulares de dopamina en el estriado, siendo este incremento 72% mas bajo que el generado por la clotianidina sola. Nuestros resultados sugieren que el efecto de la clotianidina sobre la liberacion estriatal de dopamina pueden ser reducidos por la administracion de un antagonista glutamatergico, un ihibibidor de la NOS o por antioxidantes con grupo –SH, lo cual supone un simple mecanismo de proteccion contra el dano causado por la clotianidina. EnglishIs 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.