Behavioral and neurochemical effects of acute chlorpyrifos in rats: Tolerance to prolonged inhibition of cholinesterase

The preponderance of studmes of tolerance to organophosphate (OP) cholinesterase (ChE) inhibitors indicates that functional recovery accompanies neurochemical compensations for the inhibited enzyme. Contrary to prediction, rats dosed with the OP diisopropylfluorophosphate (DFP) showed progressive and per-sistent impairment of cognitive and motor function over a 3-week period of daily exposure, despite neurochemical and phar-macological evidence of tolerance to its inhibition of ChE. To determine whether these functional effects of DFP resulted from inhibition of ChE and downregulation of muscarinic cholmnergic receptors, rats were dosed with chlorpyrifos (CPF), an OP pes-ticide 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 oi