AN INCREASED SENSITIVITY TO ALCOHOL IN RABBITS TREATED WITH A CERTAIN FACTOR CONTAINED IN A MICROSOMAL SUBFRACTION OF THE BRAIN

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  • 飯田 正一
    Department of Oral Pathology, School of Dentistry, Hokkaido University
  • 菅野 盛夫
    Research Laboratories, Takeda Chemical Industries, Ltd.
  • 中村 勝也
    Department of Pharmacology, School of Medicine, Hokkaido University

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Cochin and Kornetsky (1) showed that tolerance to the effects of a single injection of morphine in the rat as measured by the hot plate reaction could be demonstrated for periods up to one year following that single injection. Thus, they postulated that tolerance to narcotic drugs might well be an immune phenomenon or a mechanism resembling the antigen-antibody reaction.<BR> Later, Kornetsky and Kiplinger (2, 3) attempted a passive transfer of a hypothetical factor of tolerance in serum from morphine-tolerant animals (rat, dog, monkey and man) to nontolerant animals (mouse). Although they were unsuccessful in transferring the tolerance, they succeeded in demonstrating the presence of certain transferable factors in the serum of morphine-tolerant animals, since under condition of those studies, potentiation of the depressant and an analgesic action of morphine was observed. The role of the potentiating substance in the serum of the morphine-tolerant animal and the mechanism by which it potentiates morphine are as yet unknown.<BR> On the other hand, Kornetsky and Cochin (4) reported that serum from morphinetolerant rabbits attenuated morphine analgesia in mice and they assumed that the immune mechanisms involved may partially account for some of the phenomena associated with tolerance to morphine. Ungar and Cohen (5) also showed that administration of extracts of the brain taken from morphine-tolerant rats and dogs conferred tolerance on mice.<BR> The presence of the factors in the blood of morphine-tolerant animals that have attenuating or enhancing effects on morphine in nontolerant animals is an interesting finding, although the immune reaction hypothesis is no more than speculation.<BR> During a study of the effect of the treatment with a homogenate of the brain from alcohol-tolerant rabbits, on the duration of alcohol anesthesia following the intravenous injection of a test dose of alcohol, it was noted that an increased sensitivity and/or a decreased or a biphasic change in the sensitivity to alcohol was observed depending on the individual rabbit.<BR> Based on these conflicting evidences the present investigation was undertaken to define the change of sensitivity to alcohol using the normal rabbit as the recipient and the donor species.

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  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 19 (3), 409-417, 1969

    公益社団法人 日本薬理学会

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