Summary
The duration of hypnosis induced by hexobarbital, pentobarbital, chloral hydrate or barbital was markedly reduced after prolonged social isolation of male mice. Hexobarbital and pentobarbital were affected more than chloral hydrate and barbital. The onset of barbital hypnosis was not affected. The in vitro metabolism of hexobarbital by hepatic microsomal enzymes was enhanced in isolated mice with an overall increase in liver weight. Mice deprived of social interaction gained righting reflex at a higher body level of hexobarbital as compared to the undeprived animals. These data show that chronic deprivation of social stimuli in mice increased the drug-metabolizing activity of hepatic microsomes and raised arousal levels such that CNS susceptibility to drugs was altered.
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References
Allee, W. C.: Group organization among vertebrates. Science 95, 289–293 (1942).
Anderson, E. G., and D. D. Bonnycastle: A study of the central depressant action of pentobarbital, phenobarbital and diethyl ether in relationship to increase in 5-hydroxytryptamine. J. Pharmacol. exp. Ther. 130, 138–143 (1960).
Bonnycastle, D. D., M. F. Bonnycastle, and E. G. Anderson: The effect of a number of central depressant drugs upon brain 5-hydroxytryptamine levels in the rat. J. Pharmacol. exp. Ther. 135, 17–20 (1962).
Brodie, B., J. Burns, P. Lief, E. Bernstein, and E. Papper: The fate of pentobarbital in man and dog and a method for its estimation in biological material. J. Pharmacol. exp. Ther. 109, 26–34 (1953).
Bush, M. J., T. C. Bulter, and H. L. Dickison: The metabolic fate of evipal and nor-evipal. J. Pharmacol. exp. Ther. 108, 104–111 (1953).
Conney, A. H.: Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev. 19, 317–366 (1967).
Consolo, S., S. Garattini, and L. Valzelli: Sensitivity of aggressive mice to centrally acting drugs. J. Pharm. Pharmacol. 17, 594–595 (1965).
— — —: Amphetamine toxicity in aggressive mice. J. Pharm. Pharmacol. 17, 53–54 (1965a).
Cooper, J. R., and B. B. Brodie: The enzymatic metabolism of hexobarbital (Evipal). J. Pharmacol. exp. Ther. 114, 409–417 (1955).
—: Enzymatic oxidation of pentobarbital and thiopental. J. Pharmacol. exp. Ther. 120, 75–83 (1957).
Delorme, F., J. L. Fremont et M. Jouvet: Suppression du sommeil par la p-chloromethamphetamine et la p-chlorophenylaline. C. R. Soc. Biol. (Paris) 160, 2347–2351 (1966).
Dorfman, A., and L. R. Goldbaum: Detoxification of barbiturates. J. Pharmacol. exp. Ther. 90, 330–337 (1947).
Ebert, A. G., G. K. Yim, and T. S. Miya: Distribution and metabolism of barbital-C14 in tolerant and non-tolerant rats. Biochem. Pharmacol. 13, 1267 to 1274 (1964).
Friedman, P. J., and J. R. Cooper: The role of alcohol dehydrogenase in the metabolism of chloral hydrate. J. Pharmacol. exp. Ther. 129, 373–376 (1960).
Garattini, S., E. Giacalone, and L. Valzelli: Isolation, aggressiveness and 5-hydroxytryptamine turnover. J. Pharm. Pharmacol. 19, 338–339 (1967).
Giacalone, E., M. Tansella, L. Valzelli, and S. Garattini: Brain serotonin metabolism in isolated aggressive mice. Biochem. Pharmacol. 17, 1315–1327 (1968).
Jouvet, M.: Neuropharmacological basis for the role of 5-HT in sleep mechanisms. Advanc. Pharmacol. 68, 267–269 (1968).
Maynert, E. W., and H. B. Van Dyke: The absence of localization of barbital in divisions of the CNS. J. Pharmacol. exp. Ther. 98, 184–187 (1950).
Snedecor, G. W., and W. G. Cochran: Statistical Methods. Ames, Iowa: Iowa State College Press 1957.
Valzelli, L., and S. Garattini: Behavioral changes and 5-hydroxytryptamine turnover in animals. Advanc. Pharmacol. 68, 249–260 (1968).
Welch, B. L., and A. S. Welch: Graded effect of social stimulation upon d-amphetamine toxicity, aggressiveness and heart and adrenal weight. J. Pharmacol. exp. Ther. 151, 331–338 (1966).
Welch, A. S., and B. L. Welch: Effect of stress and p-chlorophenylalanine upon brain serotonin, 5-hydroxyindole acetic acid and catecholamines in grouped and isolated mice. Biochem. Pharmacol. 17, 699–708 (1968).
Wenzel, D. G., and H. Lal: The relative reliability of the escape reaction and righting reflex sleeping times in the mouse. J. Amer. pharm. Ass., sci. Ed. 48, 90–91 (1959).
Yen, C. Y., R. L. Stanger, and N. Millman: Ataractic suppression of isolationinduced aggression behavior. Arch. int. Pharmacodyn. 123, 179–185 (1959).
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This investigation was supported by PHS Training Grant No. 1T01ES 00104 from the Division of Environmental Health Sciences.
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Baumel, I., DeFeo, J.J. & Lal, H. Decreased potency of CNS depressants after prolonged social isolation in mice. Psychopharmacologia 15, 153–158 (1969). https://doi.org/10.1007/BF00407048
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DOI: https://doi.org/10.1007/BF00407048