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A mechanism for the development of tolerance to amphetamine in rats

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  • Animal Studies
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Abstract

During chronic administration of 16–32 mg/kg i. p. of dl-amphetamine sulphate in rats tolerance to the drug has been found to develop with regard to hyperthermia, anorexia, increased urinary excretion or noradrenaline and adrenaline, but not to stereotype behaviour and increased motor activity. The hypothesis, that the accumulation of p-hydroxynorephedrine, a metabolite of amphetamine in this species, might be involved in the tolerance to amphetamine as a false transmitter in central and peripheral noradrenaline neurons was tested. Rats were pretreated with p-hydroxyamphetamine, 40 mg/kg i. p. 20 h before the injection of amphetamine, 20 mg/kg i.p. After pretreatment with p-hydroxyamphetamine, which is converted to p-hydroxynorephedrine in central and peripheral NA neurons, the effects of amphetamine on body temperature, and urinary excretion of noradrenaline were decreased, while the increased motor activity, the stereotype behaviour, the anorexia and the urinary adrenaline excretion were unaffected. It is concluded that p-hydroxynorephedrine might be involved in the tolerance to the peripheral but probably not to the central effects of amphetamine.

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Authors and Affiliations

  1. Psychiatric Research Center, Ulleråker Hospital, University of Uppsala, Uppsala, Sweden

    Tommy Lewander

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  1. Tommy Lewander
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Preliminary reports of parts of the present results have been presented at the 7th Congress of C.I.N.P., Praha, August 1970 and at the second joint meeting of the Scandinavian Society of Biological Psychiatry and the Interdisciplinary Society of Biological Psychiatry, Groningen, The Netherlands, September 1970.

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Lewander, T. A mechanism for the development of tolerance to amphetamine in rats. Psychopharmacologia 21, 17–31 (1971). https://doi.org/10.1007/BF00403992

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  • DOI: https://doi.org/10.1007/BF00403992

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