The effects of DDT, DDOH-palmitic acid, and a chlorinated paraffin on muscarinic receptors and the sodium-dependent choline uptake in the central nervous system of immature mice

Abstract

Tenday-old NMRI mice were given a single peroral dose of 1.4 μmol/kg body wt of either of the substances of DDT (0.5 mg), DDOH-PA (a DDT metabolite conjugate to palmitic acid; 0.7 mg), or polychlorohexadecane (PCHD, a synthesized chlorinated paraffin; 1.0 mg). The mice were killed either 24 hr or 7 days after treatment, and crude synaptosomal fractions (P2) were prepared from the cerebral cortex and hippocampus. The density of the muscarinic receptors was assayed by measuring quinuclidinyl benzilate ([ 3H]QNB) specifically bound in the P2 fraction. A significant increase in the specific [ 3H]QNB binding was observed in the cerebral cortex in DDT- and DDOH-PA-treated mice 7 days after treatment, compared to control. These results were further explored by determining the ratio of high- and low-affinity binding sites by using an agonist (carbachol)-antagonist ([ 3H]QNB) competition assay. A significant decrease in the percentage of high-affinity binding sites and a corresponding increase in the percentage of low-affinity binding sites, compared to control, were observed after DDT and DDOH-PA treatment. The presynaptically sodium-dependent choline uptake system also was studied. In mice receiving PCHD there was a significant decrease (65%) in the V max value 7 days after treatment, but no change was observed in mice receiving DDT or DDOH-PA. This study shows that the sensitivity of the cholinergic system to persistent xenobiotics acting over a long period of time may be higher in the immature mouse.