Sex Differences in Pentobarbital Sensitivity in Mice.

Westfall, B. A.; Boulos, Badi M.; Shields, Jimmie L.; Garb, Solomon

doi:10.3181/00379727-115-28953

Cited by 28 publications

(7 citation statements)

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“…A sex difference in hexobarbital sleeping time has been estab lished [16]. Male mice sleep longer than females [16]. The present study reveals that this sex difference is maximal in inbred strains and diminishes as the strains are outbred (Table IV).…”

Section: Resultsmentioning

confidence: 60%

“…Sex differences in the response of Swiss-Webster mice to pento barbital have been reported [16]. Table IV reveals that this sex difference is maximal in certain inbred strains, whereas several outbred strains fail to exhibit it.…”

Section: [10)mentioning

confidence: 87%

“…Table III shows that the standard deviations of the intra litter sleeping times are substantially lower than those for inter litter sleeping times. A sex difference in hexobarbital sleeping time has been estab lished [16]. Male mice sleep longer than females [16].…”

Section: Resultsmentioning

confidence: 99%

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Factors Altering the Responsiveness of Mice to Hexobarbital

Es¹

1968

Pharmacology

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Section: Resultsmentioning

confidence: 60%

Section: [10)mentioning

confidence: 87%

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Factors Altering the Responsiveness of Mice to Hexobarbital

Es¹

1968

Pharmacology

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“…While the studies of Westfall et al (48) were the first to report a sex difference in the rate of drug metabolism in mice, the later observations of Vesell (46,47) and Noordhoek (38) demonstrated that the presence or absence of the sex différence was strain-dependent. In each strain where a sex difference was observed in the hexobarbital sleeping time in vivo (38, 46,47) and the rate of hexobarbital oxidation (38) or ethylmorphine N-demethylation (38) in vitro, female mice either slept for a shorter period of time or metabolized the drug at a faster rate than male mice.…”

Section: Discussionmentioning

confidence: 99%

Mouse Liver N-Demethylase Activity

1978

Pharmacology

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Male-female differences in ethylmorphine N-demethylase activity and cytochrome P-450 content were studied in BALB/cJ, DBA/2J, C3H/HeJ, C57BL/10J and CRL:CD-1 mouse strains. Demethylase activity was greater for male mice than females of the BALB/cJ strain, but the inverse male-female relationship existed for CRJL:CD-1 mice. No consistent sex differences were present in the other strains. However, hepatic microsomal cytochrome P-450 content was greater in male mice of all strains studied. The effect of testosterone administration (1,2 or 5 mg/day, 6 days, s.c.) was investigated in intact female mice of each strain. BALB/cJ mice demonstrated a dose-dependent increase in body and liver weights, whereas all five strains displayed increased microsomal protein content in response to the administration of testosterone. Testosterone produced a dose-related increase in ethylmorphine N-demethylase activity and cytochrome P-450 content of BALB/cJ mice. An increase in cytochrome P-450 content of C3H/HeJ mice was the only other response observed following testosterone treatment. These observations support the following conclusions: (1) only certain mouse strains demonstrate a sex difference in ethylmorphine N-demethylase activity and in those strains males may have higher or lower activity than females; (2) sex differences in cytochrome P-450 content are not accompanied by predictable differences in demethylase activity; (3) testosterone stimulation of hepatic microsomal protein content represents one type of androgen action whereas effects on demethylase activity and cytochrome P-450 content represent another, and (4) hepatic microsomal N-demethylase activity is under genetic control such that androgen effects on this activity in adult mice are strain-specific.

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“…Thus, Quinn, showed that male sex hormone shortened barbiturate sleeping time in female rats, whilst female sex hormone prolonged the effects of barbiturate in male rats. In contrast, although testosterone shortened the effect of hexobarbitone in female mice, the oestrogenic agent stilboestrol also shortened sleeping-time in male mice (Westfall, Boulos, Shields & Garb, 1964). Also, Gessner, Acara, Baker & Edelman (1967) showed that chronic pretreatment of both male and female mice with sex hormones caused opposite effects: pentobarbitone sleeping-time in male mice was prolonged by oestrogens, whilst testosterone shortened sleeping-times in both sexes.…”

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confidence: 95%

The effects of oestrogens and progestins on the response of mice to barbiturates

Blackham

Spencer

1969

British J Pharmacology

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1. Mestranol (oestrogen) prolonged, whilst lynestrenol (progestin) reduced, the duration of pentobarbitone and hexobarbitone sleep in mice, whilst the effects of barbitone were not altered. 2. The effects of these steroids on pentobapbitone sleep were dose-related, did not show tachyphylaxis, and produced optimal effects after only 4 days pretreatment.3. The effects of lynestrenol were abolished by SKF 525A, whilst those of mestranol were markedly potentiated, suggesting a different mechanism and/or locus of action for mestranol and SKF 525A. 4. Examination of plasma levels of pentobarbitone in mice pretreated with mestranol, lynestrenol or SKF 525A showed that lynestrenol increased whilst mestranol and SKF 525A reduced the rate of clearance of barbiturate from the plasma. 5. The effects of lynestrenol disappeared when pentobarbitone was prevented from inducing hypothermia, whilst some significant prolongation of pentobarbitone sleep persisted in mestranol treated mice. This suggested that the ability to potentiate hypothermia was not the sole mechanism by which the effects of pentobarbitone were enhanced by mestranol. 6. It is concluded these steroids alter the duration of aiction of pentobarbitone (and hexobarbitone) by changing the rate of barbiturate metalbolism. In the case of mestranol, this might be a combination of an effect upon basal metalbolic rate (enhancing hypothermia) and a direct effect on the liver. An effect upon renal clearance cannot be excluded by these results.

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Sex Differences in Pentobarbital Sensitivity in Mice.

Cited by 28 publications

References 0 publications

Factors Altering the Responsiveness of Mice to Hexobarbital

Factors Altering the Responsiveness of Mice to Hexobarbital

Mouse Liver N-Demethylase Activity

The effects of oestrogens and progestins on the response of mice to barbiturates

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