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

Toxicol Appl Pharmacol. 1986 Sep 15;85(2):121-7. doi: 10.1016/0041-008x(86)90105-5.


Ten-day-old NMRI mice were given a single peroral dose of 1.4 mumol/kg body wt of either of the substances of DDT (0.5 mg), DDOH-PA (a DDT metabolite conjugated 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 Vmax 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Choline / metabolism*
  • DDT / analogs & derivatives*
  • DDT / toxicity*
  • Female
  • Male
  • Mice
  • Palmitic Acids / toxicity*
  • Paraffin / toxicity*
  • Receptors, Muscarinic / analysis
  • Receptors, Muscarinic / drug effects*
  • Sodium / pharmacology*


  • Palmitic Acids
  • Receptors, Muscarinic
  • 2,2-bis(4-chlorophenyl)ethanol-palmitic acid
  • Paraffin
  • Sodium
  • DDT
  • Choline