Neonatal exposure to 3,3′,4,4′-tetrachlorobiphenyl: changes in spontaneous behaviour and cholinergic muscarinic receptors in the adult mouse

Abstract

We have previously reported that 3,3′,4,4′-tetrachlorobiphenyl (TCB) affects muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain when given to suckling mice at the age of 10 days. As shown in the present study, such early exposure to TCB may also lead to a permanent change in the MAChR and disturbed behaviour of the mice as adults. Male NMRI mice were given two single oral doses of TCB, 0.41 or 41 mg/kg body wt, and a 20% fat emulsion vehicle (10 ml)/kg body wt. The behavioural test at adult age of 4 months indicated a significant change in spontaneous motor behaviour in the TCB-treated mice. In mice receiving the highest dose of TCB there was also a minor increase (5%), although significant, in the density of MAChR in the hippocampus, assayed by using the tritium-labeled muscarinic antagonist, quinuclidinyl benzilate ([ 3H]QNB). As previously reported, this part of the brain was affected in the neonatal mouse, which shows that the cholinergic system during rapid development in the neonatal mouse brain is sensitive to disturbance. This may lead to permanent changes in the animals as adults, accompanied by behavioural changes.