Effects of chronic dermal exposure to nonlethal doses of methyl parathion on brain regional acetylcholinesterase and muscarinic cholinergic receptors in female rats

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 [H-3]QNB binding to muscarinic receptors in the brain regions examined. The in vitro study demonstrated that methyl parathion causes preferential inhibition of AChE and [H-3]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 [H-3]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. (C) 2002 Wiley-Liss, Inc.