Motor functions but not learning and memory are impaired upon repeated exposure to sub-lethal doses of methyl parathion.
Our previous work showed that repeated exposure to methyl parathion (MP) caused a prolonged inhibition of acetylcholinesterase (AChE) activity (approximately 80%) and down-regulation of M(1) and M(2) muscarinic receptors (up to 38%) in rats at brain regions, including frontal cortex, striatum, hippocampus and thalamus. In the present neurobehavioral study, we found this repeated MP treatment had suppressant effects on rat's locomotor activity. However, we observed no evidence of long-term effects of MP on associative learning and memory. Our data demonstrated that repeated exposure to MP caused some functional deficits in CNS, but motor activity and associative learning/memory process might differ in the sensitivity to its toxic effect. The motor dysfunctions in MP-treated rats may be mediated via reciprocal balance between cholinergic and dopaminergic systems at striatum following cholinergic over-stimulation. Our findings also suggest that the CNS deficits induced by repeated exposure to MP or other organophosphate (OP) pesticides cannot be attributed entirely to the inhibition of AChE. To accurately assess the neuro-toxic risk by occupational exposure to sub-lethal doses of MP, novel biomarkers besides in vivo anticholinesterase potency are needed.
Sun
Ting-Ting
TT
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Paul
Ian A
IA
Ho
Ing K
IK
D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008568:Memory / Q000187:drug effects; D008743:Methyl Parathion / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D008743:Methyl Parathion