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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.

journal of toxicological sciences

Role of ionotropic glutamatergic receptors and nitric oxide in the effects of flutriafol, a triazole fungicide, on the &lt;i&gt;in vivo&lt;/i&gt; striatal dopamine release