THE RELATIONSHIP OF ORAL CHLORPYRIFOS EFFECTS ON BEHAVIOR, CHOLINESTERASE INHIBITION, AND MUSCARINIC RECEPTOR DENSITY IN RAT

Behavioral changes and tissue cholinesterase (ChE) inhibition were exa mined in animals treated with the commonly used insecticide chlorpyrif os. Adult male rats were dosed by gavage with 0, 10, 30, 60, or 100 mg /kg chlorpyrifos. Rats (n = 20/dose group) were evaluated using a func tional observational battery (FOE) and an automated measure of motor a ctivity. Ail rats were tested the day before dosing and at 3.5 h (the time of peak effect) after dosing; half of these (n = 10/dose) were sa crificed immediately after testing for tissue collection. The remainin g rats were tested again at 24 h, followed by sacrifice. The following tissues were collected from each animal: half brain, individual brain areas from the other half of the brain (frontal cortex, hippocampus, striatum, hypothalamus, cerebellum, pons/medulla), retina, liver, hear t, diaphragm, quadriceps femoris muscle, and blood (separated into who le blood, plasma, and erythrocytes). ChE activity was measured in all tissues, and muscarinic receptor density was assessed as quinuclidinyl benzilate (QNB) binding in all brain regions, heart, and retina. The lowest dose produced no behavioral effects but did produce significant ChE inhibition in most tissues at 3.5 h. Higher doses produced more C hE inhibition and cholinergic signs of toxicity. Partial recovery from behavioral effects was evident at 24 h, with little or no correspondi ng recovery of ChE activity. Apparent downregulation of muscarinic rec eptor density was noted only in striatum and pons/medulla of rats trea ted with the highest dose of chlorpyrifos. Correlations for behavioral and biochemical effects were generally poor because: a) the low-dose effects on ChE inhibition were not reflected in behavioral signs, and b) behavioral signs showed recovery at 24 h, whereas ChE activity did not. Examination of data for individual rats indicated that >60% of br ain ChE inhibition was reached before neurobehavioral effects were evi dent. (C) 1997 Elsevier Science Inc.