A strain comparison of physiological and locomotor responses of mice to diisopropylfluorosphosphate

The effects of acute treatment with the organophosphate, diisopropylfluorophosphae (DFP), were studied in three inbred mouse strains. C57BL, DBA and C3H. A battery of physiological and locomotor tests including respiratory rate, heart rate, body temperature, Y-maze activity and rotarod performance was used. Dose-response and time course studies were carried out. Approximately 15 min after injection the animals were markedly affected by the drug with maximal effects occurring approximately 2 hours after injection. Strain comparisons were made at the 2 hr time point. In all strains, males and females were affected about equally except for respiratory rate and rotarod performance in which females were slightly more affected. Strain comparisons revealed that for most of the tests the C57BL mice were most affected by the DFP and the C3H mice were least affected. For the heart rate test the DBA mice were the most sensitive. Previous studies from our laboratory have demonstrated a similar rank ordering of the strains in their responses to oxotremorine and nicotine. The strain differences in response to these agents is not easily explained by differences in number or affinity of brain muscarinic or nicotinic receptors. The genetic influence on cholinergic drug response may involve receptor coupling mechanisms.