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REPEATED INHIBITION OF CHOLINESTERASE BY CHLORPYRIFOS IN RATS: BEHAVIORAL, NEUROCHEMICAL AND PHARMACOLOGICAL INDICES OF TOLERANCE
Citation:
Bushnell, P., K. Kelly, AND T. Ward. REPEATED INHIBITION OF CHOLINESTERASE BY CHLORPYRIFOS IN RATS: BEHAVIORAL, NEUROCHEMICAL AND PHARMACOLOGICAL INDICES OF TOLERANCE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/535 (NTIS PB95148979), 1994.
Description:
Daily sc injections of the organophosphate (OP) diisopropylfluorophosphate (DFP) caused prolonged inhibition of cholinesterase (ChE) activity in whole blood and brain and downregulation of muscarinic receptors in the CNS; these changes were accompanied by progressive, persistent deterioration of working memory and motor function (Bushnell et al., J. Pharmacol. xp. her. 256:741-750, 1991). hlorpyrifos (diethyl-3,5,6-trichloro-2-pyridyl phosphorothionate, CPF), an OP insecticide, caused neurochemical changes of the same magnitude and duration, but transient working memory impairment and motor slowing after a single sc injection (Bushnell et al., J. Pharmacol. xp. her. 266:1007-1017, 1993). n the present study, weekly injections of CPF (0, 15, 30, or 60 mg/k-g sc) inhibited ChE activity in whole blood of rats by 60% - 90% after 5 weeks; the highest dose also induced tremor, working memory impairment and motor slowing in daily delayed matching-to-position/visual discrimination (DMTP/VD) tests. educing the CPF injection frequency to every other week relieved the inhibition of whole blood ChE activity (50% - 75% of control) and ameliorated all the behavioral deficits. einstatement