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Main Title Behavioral and neurochemical effects of acute Chlorpyrifos in rats : tolerance to prolonged inhibition of cholinesterase /
Author Bushnell, Philip J. ; Bushnell, P. J. ; Pope, C. N. ; Padilla, S.
Other Authors
Author Title of a Work
Pope, Carey N.
Padilla, Stephanie.
CORP Author Health Effects Research Lab., Research Triangle Park, NC. Neurotoxicology Div. ;Northeast Louisiana Univ., Monroe. School of Pharmacy.
Publisher [Environmental Protection Agency],
Year Published 1994
Report Number EPA/600/J-94/041;
Stock Number PB94-137130
OCLC Number 30456955
Subjects Cholinesterase inhibitors--Physiological effect ; Insecticides--Physiological effect ; Organophosphorus compounds--Physiological effect
Additional Subjects Dursban ; Cholinesterase inhibitors ; Toxicity ; Neurochemistry ; Behavior ; Rats ; Body weight ; Brain ; Blood ; Muscarinic receptors ; Induced hypothermia ; Oxotremorine ; Reprints ;
Library Call Number Additional Info Location Last
ELBD RPS EPA 600-J-94-041 repository copy AWBERC Library/Cincinnati,OH 10/14/2020
NTIS  PB94-137130 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 1 volume
To determine whether these functional effects of diisopropylfluorophosphate (DFP) resulted from inhibition of cholinesterase (ChE) and downregulation of muscarinic cholinergic receptors, rats were dosed with chlorpyrifos (CPF), an OP pesticide which inhibits blood and brain ChE of rats for weeks after a single injection. Long-Evans rats were trained to perform an appetitive test of memory and motor function and were then injected s.c. with 0, 60, 125 or 250 mg/kg of CPF in peanut oil and tested 5 days/week for 7 weeks. Unconditioned behavior was also rated for signs of cholinergic toxicity. CPF inhibited ChE activity in whole blood in a dose-related manner for more than 53 days. The degree and time course of ChE inhibition in blood and brain and the downregulation of muscarinic receptors in brain after 125 mg/kg of CPF closely paralleled the previously reported effects of 25 daily injections of 0.2 mg/kg of DFP. In addition, CPF-treated rats were subsensitive to oxotremorine-induced hypothermia for at least 32 days after CPF. However, functional deficits (in working memory and motor function) appeared within 2 days after injection of CPF and recovered within 3 weeks, long before ChE activity and receptor density returned to control levels. Thus, the effects of CPF were neither progressive nor as persistent as those seen during daily DFP injections. This difference suggests that the DFP-induced behavioral changes observed previously cannot be attributed entirely to its effects on ChE activity and changes in (3H)quinuclidinyl benzilate binding. (Copyright (c) 1993 by The American Society for Pharmacology and Experimental Therapeutics.)
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