Neonatal exposure to a type-I pyrethroid (bioallethrin) induces dose—response changes in brain muscarinic receptors and behaviour in neonatal and adult mice

Abstract

This study shows that neonatal exposure to the insecticide bioallethrin has a dose-dependent effect on muscarinic cholinergic receptors (MAChR) in the neonatal mouse, leading to permanent changes in MAChR and in spontaneous behaviour in adult mice. Neonatal NMRI mice, given oral doses of either bioallethrin or the vehicle, once daily between the 10th and 16th postnatal day, were killed at the age of 17 days or 1 week after the spontaneous motor behaviour tests at 4 months. The MAChR were assayed in the cerebral cortex by using the antagonist quinuclidinyl benzilate ([ 3H]QNB) and the agonist carbachol. In the 17-day-old mice bioallethrin exposure elicited a significant dose-dependent increase in the specific [ 3H]QNB binding. The competition study showed that the proportion of low-affinity binding was significantly increased in the 17-day-old mice compared with controls. In the adult mouse there was a significant dose-dependent decrease in specific [ 3H]QNB binding. In these adult mice the behavioural variables ‘locomotion’ and ‘total activity’ showed significant ( P ≤ 0.01) dose-dependent increases at all doses up to and including 0.70 mg/kg b.wt.