Mechanisms of action of paraoxon, an organophosphorus pesticide, on in vivo dopamine release in conscious and freely moving rats
| Autor: | Daniel Fajardo, M. Alfonso, Lilian Rosana Ferreira Faro, Lorenzo Justo, R. Durán |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Microdialysis Dopamine Striatum Pharmacology Paraoxon Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Organophosphorus Compounds 0302 clinical medicine medicine Animals Pesticides Wakefulness Dopamine transporter biology Cell Biology Reserpine Corpus Striatum Rats Nomifensine 030104 developmental biology Parathion chemistry biology.protein Female 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neurochemistry International. 124:130-140 |
| ISSN: | 0197-0186 |
| DOI: | 10.1016/j.neuint.2019.01.001 |
| Popis: | Paraoxon is the active metabolite of parathion, an organophosphorus pesticide which can cause neurotoxic effects in animals and humans. In the present work, we investigated the effects of 5 mM paraoxon on striatal dopamine, DOPAC and HVA levels in conscious and freely moving rats, after treatment with TTX, reserpine, nomifensine, KCl, Ca++-free/EDTA medium, AP-5 or L-NAME. The intrastriatal administration of paraoxon for 60 min, through the microdialysis probe, significantly produced an increase of the dopamine to 1066 ± 120%, relative to basal levels. Administration of paraoxon to 20 μM TTX, 10 mg/kg reserpine or Ca++-free/EDTA medium-pretreated animals decreased the dopamine levels to 73%, 81%, and 70%, respectively, when compared with the effect of 5 mM paraoxon. Infusion of 50 μM nomifensine induced a maximal increase in extracellular dopamine levels to 1435 ± 387%, and when nomifensine was coadministered with paraoxon, striatal dopamine levels increased to 2429 ± 417%, an increase that was ∼230% higher that observed with the administration of the pesticide alone. Coinfusion of KCl and paraoxon produced an increase in extracellular dopamine to 1957 ± 445%, that was significantly higher than that observed with POX or KCl (1104 ± 220%) administered individually. Pretreatment with 650 μM AP-5 or 100 L-NAME reduced the effect of paraoxon on extracellular dopamine levels by 49.1% and 53.7%, respectively. Our results suggest that paraoxon induces dopamine release by a vesicular-, Ca++-, and deporalization-dependent mechanism, being independent of dopamine transporter. In addition, the paraoxon-induced dopamine release is mediated by glutamatergic and nitrergic neurotransmitter systems. |
| Databáze: | OpenAIRE |
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