Abstract
A selective breeding study was undertaken to test the hypothesis that genetic factors are involved in sensitivity of physiological and behavioral variables in rats to the irreversible anticholinesterase diisopropyl fluorophosphate (DFP). Three variables (drinking behavior, body weight, and core body temperature) were used as indices of the effects of DFP (1 mg/kg, i.m.) and selection was based on a composite score that gave equal weight to each variable. From the original parents, the six most resistant males were mated with the six most resistant females and the six most sensitive males were mated with the six most sensitive females. Subsequent generations were produced by mating the six most resistant pairs from the resistant line and the six most sensitive pairs from the sensitive line. When separation between the two lines appeared well advanced (F5), randomly bred males and females were introduced into the testing procedure. Regression analyses confirmed that the selective breeding procedure was successful in establishing a line with increased sensitivity to DFP, but that it failed to produce a line more resistant than the original population. Analyses of variance of the results for the F6, F7, and F8 generations revealed that the sensitive line was more sensitive than either the randomly bred line or the resistant line, while the latter two groups were not significantly different from each other. Biochemical studies indicated that the genetic differences in sensitivity to DFP were not related to differences in cholinesterase or acetylcholinesterase activity.
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Overstreet, D.H., Russell, R.W., Helps, S.C. et al. Selective breeding for sensitivity to the anticholinesterase DFP. Psychopharmacology 65, 15–20 (1979). https://doi.org/10.1007/BF00491972
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DOI: https://doi.org/10.1007/BF00491972