Ma_2003_J.Neurosci.Res_71_138

The in vivo and in vitro effects of methyl parathion, a phosphorothionate insecticide, on cholinergic neurotransmitter systems in the brain of rats were investigated. Three groups of adult female rats received 0, 0.1, or 1.0 mg/kg methyl parathion via dermal exposure for 95 days. Exposure to 0.1 mg/kg methyl parathion produced inhibition of AChE in the caudate-putamen and thalamic nuclei, whereas 1.0 mg/kg resulted in inhibition of AChE in most brain regions. The same doses of methyl parathion had no effect on [(3)H]QNB binding to muscarinic receptors in the brain regions examined. The in vitro study demonstrated that methyl parathion causes preferential inhibition of AChE and [(3)H]QNB binding in specific brain regions. As an inhibitor of AChE, methyl paraoxon was 1,000-fold more potent than was methyl parathion. Similarly, methyl paraoxon showed brain region-specific inhibition of the enzyme. Generally, the brain stem was highly sensitive to organophosphate-induced inhibition of AChE activity and [(3)H]QNB binding. Because central respiratory neurons gather in the brain stem, preferential effects there and in other brain regions may underlie lethal toxicity of methyl parathion and other organophosphates.