151. 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.
- Author
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Santana MB, Rodrigues KJ, Durán R, Alfonso M, Vidal L, Campos F, De Oliveira IM, and Faro LR
- Subjects
- Animals, Basal Ganglia metabolism, Calcium metabolism, Chromatography, High Pressure Liquid, Dopamine Plasma Membrane Transport Proteins drug effects, Dopamine Plasma Membrane Transport Proteins metabolism, Dopamine Uptake Inhibitors, Electrochemical Techniques, Exocytosis drug effects, Female, Nomifensine pharmacology, Potassium metabolism, Rats, Rats, Sprague-Dawley, Reserpine pharmacology, Sodium metabolism, Sodium Channel Blockers pharmacology, Tetrodotoxin pharmacology, Time Factors, Basal Ganglia drug effects, Dopamine metabolism, Fungicides, Industrial toxicity, Locomotion, Microdialysis, Triazoles toxicity
- Abstract
The purpose of the present work was to assess the effects of flutriafol, a triazole fungicide, on in vivo dopamine (DA) release from rat striatum, using brain microdialysis coupled to high-performance liquid chromatography with electrochemical detection (HPLC-EC). Intrastriatal administration of flutriafol (1, 6 and 12 mM) produced significant concentration-dependent increases in DA levels to 218.5+/-51%, 1376+/-245% and 3093+/-345% compared with basal values, respectively. Those increases in DA levels could be due to an increased DA exocytotic release and/or a change in the activity of DA transporter (DAT). Thus, we investigated the effects of flutriafol (6mM) under Ca(++)- or Na(+)-free conditions, and after pretreatment with reserpine and TTX. When flutriafol was perfused in either Ca(++)- or Na(+)-free Ringer, the DA levels reduced 92% and 70%, respectively; perfusion of flutriafol in TTX-treated (10 microM) or reserpine-pretreated animals (10mg/kg), reduced the levels of DA to 73% and 86%, respectively. Co-infusion of flutriafol and nomifensine (20 microM) shows that the flutriafol-induced DA release did not involve the DAT. Our results suggest that flutriafol induces DA release via vesicular-, Ca(++)-, Na(+)- and TTX-dependent mechanism, being independent of DAT.
- Published
- 2009
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