STRAIN AND AGE VARIATIONS IN HEXOBARBITAL RESPONSE

¹ Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California

In the neonate, drug toxicity is atrributed to poorly developed hepatic drug-metabolizing ability. The possibility that inheritance of toxic receptivity may differ from that of detoxication capability was investigated. Also, differences in drug metabolism throughout development were studied in three inbred strains of mice. Hexobarbital was injected intraperitoneally in mice of different ages and the two effects measured were: 1) hypnotic (as loss of righting reflex) and 2) lethal (as number of deaths 12 hr after injection) . Hexobarbital metabolism was measured in vitro using liver homogenates as the enzyme source. Distinct differences between the strains were found in both of these parameters. Sleeping time correlated with capacity of the liver to metabolize hexobarbital. The strain which exhibited the least hypnotic effect had the highest lethal effect. A hypothetical explanation relates toxicity to a metabolic product of hexobarbital. The variations in sleeping time between strains, apparently genetically determined, were manifest throughout postnatal development beginning at 1 day of age. Within a given strain the results were also influenced by other factors: sleeping time decreased gradually with age, except for marked decline at 3 weeks of age coincident with weaning and increased physical activity; sleeping times were less in females than in males; in females there was a variation in sleeping time with the estrus cycle.

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