The effect of a previous injection of an anticholinesterase, dyflos, on the sensitivity of rats to two centrally acting drugs, pentobarbitone and leptazol, has been measured. The sensitivity was determined at 12 and 35 days after birth and in full-grown animals. Though the dose of dyflos was of the order of two-thirds of the LD50, it did not affect the sensitivity of the young animals to sodium pentobarbitone and leptazol administered 20 hours later. The full-grown animals which had received dyflos in arachis oil were more sensitive to sodium pentobarbitone than litter mates which had received an injection of arachis oil only; this difference was significant at the 0.1% level. Thc dyflos treatment did not significantly affect the sensitivity to leptazol. A previous paper (Elkes, Eayrs, and Todrick, 1955) described an attempt to modify the development of central nervous function in the rat by the injection of an anticholinesterase, dyflos (diisopropyl fluorophosphonate, DFP), regularly from the third day after birth. The results were negative. As an alternative approach to the study of the significance of cholinesterase in the central nervous system, the effect of a previous injection of DFP on the sensitivity of growing and full-grown rats to two centrally acting drugs, sodium pentobarbitone and leptazol, has been measured. The results suggest that DFP affects the response of the full-grown animal to sodium pentobarbi-tone. They also indicate that the sensitivity of the rat to sodium pentobarbitone and leptazol varies with age. MATERIALS AND METHODS The object of the experiment was to compare the ED50 of rats previously treated with DFP with that of untreated animals. The measurement of an ED50 presents no unusual difficulties, but, since the population variance is high, it is desirable to use litter mates of the same sex at the different dose levels. This can be arranged if the number of doses employed is four. However, the comparison of the ED50 for two sets of experimental conditions rendered such a procedure impracticable. The principle adopted was therefore to balance the DFP and control groups at a given dose in respect of litter mates of the same sex, but to pay less regard to the distribution of litters and sexes between the different doses. Another limitation in the design of the experiment arose from the use of young animals. It had previously been found that the effects of DFP were disabling for some hours (Elkes et al., 1955); in the competitive conditions of a large litter, the treated animals tended to be eliminated by the mother. A modification of the standard split litter technique was therefore adopted. Design of Experiment Young Rats.-The experiment involved 42 litters born over a period of 18 days, and a total of 342 rats; they were of the Department of Pharmacology, Birm-ingham, strain. Each litter was split as close to a 3: 3 : 4 ratio as possible, sexes being balanced during the operation; four-tenths of each of three litters were joined to form a control group, the others to form two exper...
