STUDIES UPON THE SEX-DIFFERENCE IN RATS IN TOLERANCE TO CERTAIN BARBITURATES AND TO NICOTINE

¹ From the Department of Pharmacology of the American University of Beirut, Syria the Department of Physiology of the University of Chicago, and the Deparment, of Physiology and Pharmacology of the University of Nebraska, Lincoln

1. Using duration of hypnosis and incidence of mortality as criteria, no sex-difference was found in the white or hybrid rat to barbiturates with two short side-chains, or one such with an iso-aliphatic or a phenyl group (barbital, ipral, alurate, diallyl barbiturate, nostal, dichlor allyl barbiturate, phenobarbital). No sex-difference was found to chloral hydrate.

2. A slight to moderately higher male resistance was seen with barbiturates having one short and one longer straight aliphatic chain (neonal, ortal; also to ethyl 2-methyl-amyl barbiturate).

3. Much higher male resistance was present with barbiturates having one short and one long, forked chain (not of the iso type) or a cyclohexenyl group (amytal, pentobarbital, seconal, pernoston and its chlorine homologue, rectidon (sigmodal), phanodorn and evipal), or those with a methylated nitrogen (eunarcon, evipal). These are the short acting ones, but nostal is also short acting and the rat exhibits no sex-difference to it.

4. No sex-difference was found to evipal in certain other species of animals (dog, cat, rabbit, guinea pig, mouse, frog). In mice sex-difference was also absent to amytal, but was present in case of pernoston to a slight extent.

5. Castration of adult male rats lengthened hypnosis following four of the sex-difference barbiturates, though to a variable degree (pernoston, evipal, amytal and nembutal, given in descending order), but not following barbital, a non-sex-difference barbiturate. Castration of male rabbits did not lengthen depression following evipal administration.

6. Neither spaying of adult female rats, nor oestrus influenced the response to evipal.

7. In rats at the age of three to four weeks no sex-difference could be found to evipal or pentobarbita!. In such young females the average recovery time with evipal administration was gradually, moderately lengthened as they grew older and became stable at the age of three months. In the young male it was abruptly shortened, becoming stable at about half the level of the female recovery time at the age of about four months. The curve of the recovery time of castrated baby male rats followed that of the normals rather closely for about five weeks, then rose abruptly to reach a level nearer the female curve.

8. Prolonged, heavy administration of male hormone from human urine shortened the evipal depression significantly in normal and spayed female rats, but did not make it as short as that of normal males. Androsterone was ineffective when given three months after spaying. The lengthening effect of castration upon the male rat response to evipal was partly counteracted by urinary male hormone.

9. Unilateral adrenalectomy did not influence the recovery time in male rats given evipal. Total nephrectomy did not alter the sex-difference, neither did briefer starvation, nor sterility due to lack of vitamin E.

10. No assayable amounts of male hormone were present in the rat urine of either sex; no estrogenic hormone was found in female urine, but 10 gammas per liter were present in the male urine.

11. A statistical study of rat mortality following the administration of nicotine to 336 rats showed that it took about 25 per cent more to kill one-fourth, one-half or three-fourths of a given group of males as compared with females.