Long-term neurochemical and behavioral effects induced by acute chlorpyrifos treatment.
A single dose of the organophosphate insecticide O,O'-diethyl-O-3,5,6- trichloro-2-pyridylphosphorothioate [chlorpyrifos (CPF), 279 mg/kg, SC] caused extensive inhibition of cortical and striatal cholinesterase (ChE) activity in adult rats at 2 (94-96%), 4 (82-83%), and 6 (58-60%) weeks after treatment. These persistent changes in ChE activity were concomitant with reductions in muscarinic receptor binding sites in cortex (34, 33, and 18% reduction in Bmax) and striatum (48, 40, and 23% reduction in Bmax) at 2, 4, and 6 weeks after exposure. Neither ChE activities nor muscarinic receptor densities were different from control levels at 12 weeks after exposure. CPF treatment caused a reduction in locomotor activity for the first 2 days after treatment, after which basal activity levels were not different from controls. CPF-treated rats showed higher activity relative to controls, however, following challenge with scopolamine (1 mg/kg, IP) at 2, 4, 6, 8, and 12 weeks after treatment. These data indicate that acute exposure to CPF in adult rats can cause long-term neurobehavioral changes that may persist following the recovery of neurochemical parameters associated with exposure and tolerance to cholinesterase inhibitors.
Pope
C N
CN
Division of Pharmacology and Toxicology, School of Pharmacy, Northeast Louisiana University, Monroe 71209-0470.
Chakraborti
T K
TK
Chapman
M L
ML
Farrar
J D
JD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D004390:Chlorpyrifos / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology
D011976:Receptors, Muscarinic; D012601:Scopolamine; D002802:Cholinesterases; D004390:Chlorpyrifos