Acute exposure to organochlorine pesticides does not affect striatal dopamine in mice

Abstract

The purpose of this study was to evaluate the possible association between the risk of developing Parkinson's disease (PD) and exposure to organochlorine pesticides in the mouse model. Animals were treated with a single subcutaneous injection of either dieldrin (40 and 80 mg/kg) or 2,4-dichlorophenoxyacetic acid (100 and 200 mg/kg, 2,4-D) and levels of dopamine (DA) and DA metabolites were measured in the striatum at the 7-day time point. Dieldrin exposure did not affect the striatal concentrations of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Administration of 2,4-D did not produce any changes with the exception of a slight (15%), but statistically significant decrease in DOPAC using the higher dose of the pesticide. No neurochemical signs of dopaminergic injury were found following the combined treatment with either dieldrin or 2,4-D plus diethyldithiocarbamate (DDC), a compound known to potentiate the effects of the dopaminergic toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, neither dieldrin nor 2,4-D caused additional damage in animals previously lesioned with MPTP. Data failed to support the hypothesis that acute exposure to organochlorine compounds or synergistic interactions involving these pesticides may cause significant damage to dopaminergic terminals and therefore contribute to nigrostriatal degeneration in PD.

Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus

“…Similarly, mice injected with a single subcutaneous injection of dieldrin (40 and 80 mg/kg) after 7 days showed no significant changes in levels of striatal dopamine (DA) and DOPAC (Thiffault et al, 2001). However, in some studies, dieldrin has also been shown to deplete DA production in mammals in vivo .…”

Role of reactive oxygen species in the neurotoxicity of environmental agents implicated in Parkinson's disease

“…It remains to be determined if this potentially toxic event is a direct result of dieldrin interaction with the transporter or related to mitochondrial energy failure. While single high dose administration of dieldrin in mice fails to induce any significant changes in striatal DA and metabolite concentrations [130], chronic dosing paradigms show depletion of brain DA levels in a variety of animal models [125,[131][132][133]. Furthermore, changes in dopamine transporter and VMAT2 levels [134,135], decreased DA metabolite levels, and increased cysteinyl-catechol adducts in the striatum [125] suggest alterations in the uptake, storage, and metabolism of DA in the nigrostriatal pathway.…”

Herbicides and the Risk of Neurodegenerative Disease

“…Although dieldrin has often been administered directly to mice (Hatcher et al, 2007;Richardson et al, 2006;Thiffault et al, 2001) these studies have used varying treatment parameters, meaning that often conflicting results must be evaluated carefully. The ban on dieldrin also means that there is less interest in fully establishing its status as a factor in neurodegeneration, and it is unlikely to see further development as a model of PD.…”