Exposure to DDT during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behaviour in adult mice

Abstract

DDT [1,1,1-trichloro-2,2- bis(p-chlorophenyl)ethane] is a potent neurotoxicant in both vertebrate and invertebrate species. We have previously reported that neonatal exposure to DDT affects the muscarinic cholinergic receptors (MAChR) in the cerebral cortex in the neonatal mouse, leading to permanent disturbances in the cholinergic system and behaviour of the animals as adults. In order to determine if there is a critical period for these effects, mice at the ages of 3-days, 10-days and 19-days were given a single low oral dose of DDT (0.5 mg/kg b.wt.). At adult age (4 months) the mice were tested for spontaneous behaviour: ‘locomotion’, ‘rearing’ and ‘total activity’, and were subsequently sacrificed for measurement of the density of MAChR and subpopulations of MAChR in the cerebral cortex by using the muscarinic antagonist quinuclidinyl benzilate, [ 3H]QNB, and agonist carbachol, respectively. A significant increase in spontaneous motor behaviour and a significant decrease in MAChR density in the cerebral cortex was only observed in adult mice receiving DDT at the age of 10 days. The induction of these disturbances is limited to peaks in the development of spontaneous behavioural activity and MAChR in the neonatal rodent.