Neurotoxic effects of two different pyrethroids, bioallethrin and deltamethrin, on immature and adult mice: changes in behavioral and muscarinic receptor variables.

We have recently shown that two pyrethroids, bioallethrin and deltamethrin, affect muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain when given to suckling mice during the period of rapid brain growth. Such early exposure to these pyrethroids can also lead to permanent changes in the MAChR and behavior in the mice as adults. In the present study, male NMRI mice were given bioallethrin (0.7 mg), deltamethrin (0.7 mg), or a 20% fat emulsion vehicle (10 ml) per kilogram of body weight per os once daily between the 10th and 16th postnatal day. The mice were subjected to behavioral tests upon reaching the age of 17 days and at 4 months. Within 1-2 weeks after the behavioral tests the mice were killed by decapitation and crude synaptosomal fractions (P2) were prepared from the cerebral cortex, hippocampus, and striatum. The densities of MAChR were assayed by measuring the amounts of quinuclidinyl benzilate ([3H]QNB) specifically bound in the P2 fraction. The proportions of high-affinity (HA) and low-affinity (LA) binding sites of MAChR were assayed in a displacement study using [3H]QNB/carbachol. The behavioral tests at an adult age of 4 months indicated a significant increase in spontaneous motor behavior in both bioallethrin- and deltamethrin-treated mice. There was also a significant decrease and a tendency toward a decrease in the density of MAChR in the cerebral cortex in mice receiving bioallethrin and deltamethrin, respectively. The proportions of HA- and LA-binding sites of MAChR were not changed. This study further supports that disturbances of the cholinergic system during rapid development in the neonatal mouse can lead to permanent changes in cholinergic and behavioral variables in the animals as adults.