Effects of diisopropylfluorophosphate on brain cholinergic systems of rats at early developmental stages

The effects of subchronic intoxication by diisopropylfluorophosphate (DFP) during pregnancy on development of brain cholinesterases (ChE) and [3H]quinuclidinyl benzilate (QNB) binding to muscarinic receptors were studied at the end of gestation and in offspring at 1, 5, 10, and 20 days after birth. Pregnant rats received on alternate days sc injections of DFP (first dose 1.1 mg/kg, subsequent doses 0.7 mg/kg) from Day 6 through Day 20. In spite of the considerable maternal toxicity of DFP, the level of brain ChE at birth and subsequent increases of enzymatic activity did not differ from those of controls. By contrast, significantly lower levels of QNB binding sites at birth were followed by a delay in development up to about 2 weeks. In the experiments using animals sacrificed on Days 20 and 21 of gestation, maternal brain ChE were consistently depressed, while in fetal brain an almost complete recovery occurred within 48 hr from the last DFP injection. Maximal number of QNB binding sites (Bmax) was decreased significantly both in maternal and fetal brain. These data indicate that tolerance mediated by receptor changes can be produced at early developmental stages, in spite of the accelerated recovery of brain ChE after treatment. In another experiment 7- to 27-day pups were treated on alternate days with sc doses of DFP (0.45 mg/kg from Day 7 to Day 19 and 0.70 mg/kg up to Day 27) and sacrificed on Day 7, 14, 20, 28, or 40. Brain ChE was reduced by 45-70%.(ABSTRACT TRUNCATED AT 250 WORDS)