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ToxSci Advance Access published online on November 4, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfh014
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received August 1, 2003; accepted October 3, 2003
© 2003 Society of Toxicology

Neurotoxicology

Neurochemical Effects of Repeated Gestational Exposure to Chlorpyrifos in Developing Rats

Jason R. Richardson 1 and Janice E. Chambers 1*

1 Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi 39762

* To whom correspondence should be addressed. E-mail: chambers{at}cvm.msstate.edu.


  Abstract

The neurochemical effects in developing rats exposed during gestation to the anticholinesterase organophosphorus insecticide chlorpyrifos (CPS) were determined. Pregnant rats were dosed daily with CPS (0, 3, or 7 mg/kg) in corn oil from gestation day (GD) 6-20. Pups were euthanized on postnatal days (PND) 1, 3, 6, 9, 12, and 30 for the determination of brain cholinesterase (ChE) and choline acetyltransferase (ChAT) activities, along with muscarinic receptor (mAChR) densities, the levels of the high affinity choline uptake (HACU) system and the vesicular acetylcholine transporter (VAChT). ChE activities were inhibited about 15 and 30% on PND1, in the low and high dosage groups respectively, and were not different from control values by PND6. mAChR densities on PND1 were reduced in the high dosage group by about 18, 21, and 17%, using 3H-N-methylscopolamine, 3H-quinuclidinyl benzilate, and 3H-4-DAMP, respectively, as ligands, and were not different from control levels by PND6. ChAT activity was decreased by about 12% in the high dosage group on PND9, 12, and 30. HACU levels, using 3H-hemicholinium-3 as the ligand, were reduced by about 25% on PND6, in the low and high dosage groups, and by about 14 and 21% on PND12 and 30, only in the high dosage group. Levels of the VAChT were reduced by a range of 13 to 31% on PND3 through 30 in the high dosage group, using 3H-AH5183 (vesamicol) as the ligand. These data suggest that gestational exposure to 7 mg/kg/day CPS results in long term alterations of pre-synaptic cholinergic neurochemistry.

Key Words: developmental neurotoxicity, chlorpyrifos, choline acetyltransferase, cholinesterase inhibition, cholinergic neurochemistry, organophosphate insecticide .


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