Neurochemical effects of repeated gestational exposure to chlorpyrifos in developing rats.
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 days (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 PND 1, in the low- and high-dosage groups, respectively, and were not different from control values by PND 6. mAChR densities on PND 1 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 PND 6. ChAT activity was decreased by approximately 12% in the high-dosage group on PND 9, 12, and 30. HACU levels, using 3H-hemicholinium-3 as the ligand, were reduced by approximately 25% on PND 6 in the low- and high-dosage groups, and by approximately 14 and 21% on PND 12 and 30, only in the high-dosage group. Levels of the VAChT were reduced by a range of 13-31% on PND 3 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 presynaptic cholinergic neurochemistry.
Richardson
Jason R
JR
Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi 39762, USA.
Chambers
Janice E
JE
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D001923:Brain Chemistry; D004390:Chlorpyrifos / Q000008:administration & dosage / Q000633:toxicity*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002802:Cholinesterases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D018811:Maternal Exposure; D026901:Membrane Transport Proteins / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins / Q000378:metabolism
D007306:Insecticides; D026901:Membrane Transport Proteins; D011976:Receptors, Muscarinic; C493459:SLC18A3 protein, human; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; C065637:choline transporter; D002795:Choline O-Acetyltransferase; D002802:Cholinesterases; D004390:Chlorpyrifos