Neurochemical and neurobehavioral effects of repeated gestational exposure to chlorpyrifos in maternal and developing rats.
Acute exposure to the organophosphate pesticide chlorpyrifos (CPF) on gestation day 12 (GD12, 200 mg/kg/ml, SC) causes extensive neurochemical changes in maternal brain but lesser changes in fetal brain. In the present study, we examined the relative neurotoxicity of repeated, lower-level CPF exposures during gestation in rats. Pregnant Sprague-Dawley rats were exposed to CPF (6.25, 12.5, or 25 mg/kg per day, SC) from GD12-19 and sampled at either GD16, GD20, or postnatal day 3 (PND3) for measurement of various maternal and developmental neurochemical markers. In contrast to the high acute dose exposure, no maternal toxicity was noted with repeated lower-level dosing. Extensive acetylcholinesterase (AChE) inhibition (83-90%) was noted in maternal brain at all three time points following repeated exposures (25 mg/kg). Higher AChE inhibition (58%) was noted in fetal brain at GD20 compared to 19-25% on PND3 in treated pups cross-fostered to control dams and in control pups cross-fostered to treated dams following repeated exposures (25 mg/kg per day). Whereas similar reductions in brain muscarinic receptor binding were noted at GD20 and PND3 in dams and developing brain between acute and repeated dosing regimens, greater changes in [3H]CD and [3H]cytisine binding were evident following repeated exposures. Righting reflex and cliff avoidance tests were markedly altered following repeated exposures. The results suggest that lower-level repeated exposures to CPF cause extensive neurochemical and neurobehavioral changes in developing rats in the absence of maternal toxicity.
Chanda
S M
SM
Division of Pharmacology and Toxicology, College of Pharmacy and Health Sciences, Northeast Louisiana University, Monroe 71209, USA.
Pope
C N
CN
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D018727:Muscarinic Antagonists / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D000110:Acetylcholinesterase; D004390:Chlorpyrifos