Pyrethroid pesticide-induced alterations in dopamine transporter function
Section snippets
Materials
Analytical grade (purity ≥98%) deltamethrin and permethrin were obtained from ChemService Inc. (West Chester, PA). 3H-dopamine (58 Ci/mmol) and 3H-WIN 35,428 (85 Ci/mmol) were purchased from Perkin-Elmer Life Sciences (Boston, MA). The rat monoclonal antibody to DAT was purchased from Chemicon (Temecula, CA) and the monoclonal anti-mouse α-tubulin was purchased from Sigma (St. Louis, MO). The goat anti-rat secondary antibody was purchased from ICN (Costa Mesa, CA) and the goat anti-mouse
Results
No overt signs of toxicity, defined as tremor, choreoathetosis, and salivation, were observed following administration of either deltamethrin or permethrin. There were also no significant changes in weight in any of the treated animals (data not shown).
Based upon previous studies demonstrating increased dopamine uptake following deltamethrin or permethrin exposure (Kirby et al., 1999, Gillette and Bloomquist, 2003), we administered deltamethrin (3 mg/kg) or permethrin (0.8 mg/kg) three times
Discussion
Previous studies have demonstrated that repeated exposure of mice to the pyrethroid pesticides, deltamethrin and permethrin, results in increased synaptosomal dopamine uptake (Kirby et al., 1999, Karen et al., 2001, Gillette and Bloomquist, 2003). In this study, we confirm these observations and extend them by demonstrating that the functional up-regulation is accompanied by increases in DAT-binding sites. In addition, we demonstrate that permethrin and deltamethrin have no direct effect on DAT
Acknowledgments
This work was supported by the US Army Medical Research and Materiel Command under Award No. 00267036 (GWM), and in part by NIH U54 ES012068 (GWM) and F32 ES013457 (JRR), and an EPA STAR Fellowship (TSG). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army, NIH, or EPA.
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