PMID- 14600285 OWN - NLM STAT- MEDLINE DCOM- 20040831 LR - 20200304 IS - 1096-6080 (Print) IS - 1096-0929 (Linking) VI - 77 IP - 1 DP - 2004 Jan TI - The effect of chlorpyrifos and chlorpyrifos-oxon on brain cholinesterase, muscarinic receptor binding, and neurotrophin levels in rats following early postnatal exposure. PG - 63-71 AB - Chlorpyrifos (CPS) is a widely used diethyl organophosphorus insecticide in agricultural settings. Household and urinary residue analysis has suggested that children in agricultural communities are at risk of exposure to diethyl organophosphorus insecticides. The effects of repeated postnatal exposure to CPS and its metabolite chlorpyrifos-oxon (CPO) on total muscarinic acetylcholine receptor (mAChR) binding, nerve growth factor (NGF) levels, and brain derived neurotrophic factor (BDNF) levels in the forebrain of neonatal rats were investigated. Peak inhibition of brain cholinesterase (ChE) for CPS and CPO was determined after acute exposure to dosages of each compound (a low and a high for each), which produced similar degrees of initial ChE inhibition. Pups were administered CPS (1.5 or 3.0 mg/kg), CPO (0.25 or 0.35 mg/kg), or the corn oil vehicle by daily gavage from postnatal day 1 (PND 1) through PND 6. This exposure paradigm resulted in persistent ChE inhibition by CPS but only transient inhibition by CPO, suggesting that, even though the initial ChE inhibition is similar between compounds, the effects of repeated exposure differ significantly. Forebrain mAChR density, as measured by the binding of 3H-QNB, and NGF levels were significantly reduced on PND 4 and 7 after CPS but not on PND 12. No effects on mAChR density or NGF levels were observed with CPO. No effects on BDNF levels were observed with either compound. The data suggest that the persistent ChE inhibition and decreased mAChR binding may play a role in the decreased NGF levels following CPS exposure. FAU - Betancourt, Angela M AU - Betancourt AM AD - Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi 39762, USA. FAU - Carr, Russell L AU - Carr RL LA - eng GR - R01 ES010386/ES/NIEHS NIH HHS/United States GR - 1 R01 ES 10386-01A1/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20031104 PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Insecticides) RN - 0 (Nerve Growth Factors) RN - 0 (Receptors, Muscarinic) RN - 5598-15-2 (O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate) RN - EC 3.1.1.8 (Cholinesterases) RN - JCS58I644W (Chlorpyrifos) SB - IM MH - Administration, Oral MH - Animals MH - Animals, Newborn MH - Chlorpyrifos/administration & dosage/*analogs & derivatives/*toxicity MH - Cholinesterases/*metabolism MH - Dose-Response Relationship, Drug MH - Female MH - Insecticides/administration & dosage/*toxicity MH - Male MH - Nerve Growth Factors/*metabolism MH - Prosencephalon/*drug effects/growth & development/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Muscarinic/*metabolism EDAT- 2003/11/06 05:00 MHDA- 2004/09/01 05:00 CRDT- 2003/11/06 05:00 PHST- 2003/11/06 05:00 [pubmed] PHST- 2004/09/01 05:00 [medline] PHST- 2003/11/06 05:00 [entrez] AID - kfh003 [pii] AID - 10.1093/toxsci/kfh003 [doi] PST - ppublish SO - Toxicol Sci. 2004 Jan;77(1):63-71. doi: 10.1093/toxsci/kfh003. Epub 2003 Nov 4.