Effects of two pyrethroids, bioallethrin and deltamethrin, on subpopulations of muscarinic and nicotinic receptors in the neonatal mouse brain

Abstract

Ten-day-old NMRI mice were given deltamethrin, bioallethrin, or the vehicle once daily for 7 days. The doses used were as follows: deltamethrin, 0.71 and 1.2 mg/kg body wt; bioallethrin, 0.72 and 72 mg/kg body wt; and 20% fat emulsion vehicle, 10 ml/kg body wt. The mice were killed 24 hr after the last administration, and crude synaptosomal fractions (P2) were prepared from the cerebral cortex and hippocampus. The densities of the muscarinic and nicotinic receptors were assayed by measuring the amounts of quinuclidinyl benzilate ([ 3H]QNB) and [ 3H]nicotine, respectively, specifically bound in the P2 fraction. The proportions of high- and low-affinity binding sites of the muscarinic receptors were assayed in a displacement study using [ 3H]QNB/carbachol. The two types of pyrethroids affected the cholinergic system in the neonatal mouse brain in two different ways. At the lower dose, which did not cause any neurotoxic symptoms, both pyrethroid types affected the muscarinic receptors in the cerebral cortex. Here deltamethrin caused an increase and decrease in the percentage of high- and low-affinity binding sites, respectively, whereas the reverse was observed after bioallethrin treatment. Deltamethrin treatment also caused an increase in the density of nicotinic receptors in the cerebral cortex. The higher doses revealed typical symptoms of pyrethroid poisoning, such as choreoathetosis and tremor for deltamethrin and bioallethrin, respectively. The symptoms declined gradually during each successive day of administration and had disappeared by Day 4. At this dose deltamethrin affected the muscarinic receptors in the hippocampus and the nicotinic receptors in the cerebral cortex, whereas bioallethrin had no apparent effect. This study further supports that the cholinergic system under rapid development in the neonatal mouse is sensitive to xenobiotics.