Comparative neurochemical and neurobehavioral effects of repeated chlorpyrifos exposures in young and adult rats.
Neonatal (7 days old) rats are markedly more sensitive than adults (3 months old) to the acute toxic effects of the insecticide, chlorpyrifos (CPF). In the present study, we have compared the effects of subacute CPF exposures in these same age groups. Repeated doses of CPF (40 mg/kg, SC, every 4 days, total of 4 doses) caused extensive inhibition of cortical, hippocampal, and striatal cholinesterase (ChE) activity in adult rats at 4 (90-92%) and 14 (71-78%) days after the last treatment. Rats treated similarly during postnatal maturation (beginning on day 7) showed a much lower degree of ChE inhibition (21-60%) at these time points. Muscarinic ([3H]quinuclidinyl benzilate, QNB) receptor binding in cortex, hippocampus, and striatum was reduced in adult brain at 4 (30-43%) and 14 (22-32%) days after the final treatment, whereas receptor densities were only marginally affected (5-11% reduction) in young rats. Basal motor activity levels were not affected in either young or adult rats as a function of CPF exposure. CPF-treated adult rats exhibited higher activity levels after challenge with scopolamine (1 mg/kg, IP) at 2, 4, 6, and 8 weeks after treatment, whereas CPF exposure did not affect the motoric response to scopolamine in rats treated during postnatal maturation. These data suggest that although neonatal rats are more sensitive to acute lethal effects from high doses of CPF, adult rats exhibit more persistent neurochemical and neurobehavioral alterations following repeated, lower-level exposures.
Chakraborti
T K
TK
Division of Pharmacology and Toxicology, School of Pharmacy, Northeast Louisiana University, Monroe 71209-0470.
Farrar
J D
JD
Pope
C N
CN
D000375:Aging / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D004390:Chlorpyrifos / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology
D015415:Biomarkers; D011976:Receptors, Muscarinic; D012601:Scopolamine; D002802:Cholinesterases; D004390:Chlorpyrifos