✍ Scribed by Holck, Harald G.O.
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The subcutaneous LDSO of picrotoxin of the adult male albino rat was 87 per cent higher than for the female (5.48 versus 2.82 mg./Kg.); 458 rats were used in these determinations. No sex variation, however, was found in case of albino mice, guinea pigs, or Syrian hamsters. Castration of adult males or females lowered the resistance to picrotoxin. Daily administration of testosterone propionate over a period of ten days increased the resistance of normal and castrated young adult females. The typical sex difference persisted i n normal rats i n which both kidneys had been removed about eighteen hours prior to administration of picrotoxin.
HE FIRST mention of sex variation to picro-Ttoxin was made by Holck (l), who reported an approximate median lethal dose of 5.9 mg. per Kg. for male and 3.5 for female hybrid rats. Although the matter of sex is not discussed, the data of Cole (2) also indicate a higher resistance of the albino male rat as compared with that of the female. A similarly marked sex difference in resistance to strychnine has been reported repeatedly (3, 4). However, i n our preliminary studies, no sex variation was found in the case of another convulsant drug, namely, Metrazol.
Fatal Dose Determinations in Albino Rats.-In the present study the median lethal doses (LDBWa) for young adult albino rats of Wistar stock were established in the two sexes. The animals were not fasted and had been kept on a uniform diet in a temperature-controlled animal room. The picrotoxin was injected subcutaneously in the abdominal area, using a 0.2% solution in distilled water. Because it has been reported that the fatal dose of picrotoxin gradually decreased in mice as the room temperature is raised from 20" to 40" (5), we kept the temperature at 27-28' during this determination. After injection each animal was kept in an individual cage. The doses were increased in steps of 15% and a total of 179 males and 186 females were injected. The dosage range and observed mortalities are shown in Table I. To cover the whole range of fatalities the highest male dose of 7.31 mg./ Kg. was added four weeks after concluding the rest of the one-day experiment carried out on both sexes simultaneously.
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of a thesis presented to the Graduate Council of the University of Florida in partial fulfilment of the requirements for the degree of Doctor of Philosophy.