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.
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.
Santana
M B
MB
Departamento de Fisiologia, Centro de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
Rodrigues
K J A
KJ
Durán
R
R
Alfonso
M
M
Vidal
L
L
Campos
F
F
De Oliveira
I M
IM
Faro
L R F
LR
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors; D055664:Electrochemical Techniques; D005089:Exocytosis / Q000187:drug effects; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D008124:Locomotion; D017551:Microdialysis; D009627:Nomifensine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000633:toxicity*
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D005659:Fungicides, Industrial; D026941:Sodium Channel Blockers; D014230:Triazoles; D009627:Nomifensine; D013779:Tetrodotoxin; C543009:flutriafol; D012110:Reserpine; D012964:Sodium; D011188:Potassium; D002118:Calcium; D004298:Dopamine