Neurotoxicity of the Organochlorine Insecticide Heptachlor to Murine Striatal Dopaminergic Pathways

• DOI: 10.1093/toxsci/61.1.100
• Publication Date: 2002-07-26T22:52:07Z
• Authors: M. L. Kirby
• Keywords: Heptachlor

Changes in biochemical status of nerve terminals the corpus striatum, one primary brain regions affected Parkinson's disease, were studied groups C57BL/6 mice treated by ip injection three times over a 2-week period with 3–100 mg/kg heptachlor. On average, maximal rate striatal dopamine uptake increased > 2-fold at doses 6 heptachlor and 1.7-fold 12 Increases attributed to induction transporter (DAT) compensatory response elevated synaptic levels dopamine. Significant increase Vmax DAT was not observed mg/kg, which suggested that toxic effects epoxide may be responsible for loss higher In support this conclusion, polarigraphic measurements basal synaptosomal respiration rates from 25 indicated marked, dose-dependent depression tissue respiration. At heptachlor, expression DAT, 5-hydroxytryptamine into cortical synaptosomes unaffected. Thus, dopaminergic found differentially sensitive This reduced sensitivity serotonergic pathways mirrored greater potency cause release preloaded vitro compared serotonin membranes. These results suggest perhaps other organochlorine insecticides, exert selective on neurons play role etiology idiopathic disease.