Evaluation of the effects and mechanisms of action of flutriafol, a triazole fungicide, on striatal dopamine release by using in vivo microdialysis in freely moving rats

Neurotoxic Effects of Triazole Fungicides on Nigrostriatal Dopaminergic Neurotransmission

“…In this way, we can observe that the neurochemical mechanism of action of triadimefon and flutriafol to induce in vivo dopamine release from rat striatum appear to be different. So, opposed to the data described for triadimefon, the results obtained by Santana et al (2009) showed that flutriafol-induced dopamine release in vivo is not due to an action of this fungicide on DAT, but through an exocytotic release. Considering the difference observed in the biochemical mechanisms of action of two pesticides belonging to the same class, some comparisons between these two studies can be considered.…”

“…It has been described that triazole fungicides triadimefon (and its metabolite triadimenol) and flutriafol produce changes in dopaminergic neurotransmission (Walker & Mailman, 1996;Gagnaire & Micillino, 2006;Santana et al, 2009). As previously described, the effects produced by triazole fungicides on the dopaminergic system began to be described at the end of 1980s and early 1990s, with initial observations of neurotoxic effects of triadimefon on the motor activity.…”

“…The effects of flutriafol on in vivo dopamine release were studied by Santana et al (2009). These authors demonstrated that in situ administration of different concentrations of this fungicide into rat striatum also induced changes in dopaminergic neurotransmission.…”

“…The results also suggest that triadimefon does not act as a dopamine releaser like amphetamine and appear to act in a similar way to GBR 12909, since the two substances induced increases in dopamine release with similar profiles. In other study Santana et al (2009) investigated the neurochemical mechanism by what flutriafol produce increases in extracellular dopamine levels in striatum of rats. To evaluate if flutriafol-induced dopamine release was due to an increased dopamine exocytotic release and/or a change in the activity of DAT, Santana et al (2009) investigated the effects of flutriafol under Ca ++ -free or Na + -free conditions, and after pretreatment with reserpine and TTX.…”

“…These results seem to indicate that dopamine release evoked by flutriafol is dependent of dopamine stored in the synaptic vesicles and on depolarization mediated by voltage-sensitive sodium channels. In another set of experiments, Santana et al (2009) studied the involvement of the DAT in the flutriafol-induced dopamine release by measuring the effect of coadministration of 6 mM flutriafol and nomifensine on dopamine release. When nomifensine or flutriafol were administered, the dopamine release increased over 16 and 14 times with respect to the basal levels, respectively (Fig.…”