Skip to main content
SpringerLink
Log in

Urinary excretion and tissue levels of catecholamines during chronic amphetamine intoxication

  • Original Investigations
  • Published:
Psychopharmacologia Aims and scope Submit manuscript

Summary

Administration of 16 mg/kg of dl-amphetamine sulphate twice daily caused a 3- to 5-fold increase in the urinary output of noradrenaline and adrenaline in rats. Bilateral splanchnic denervation abolished the urinary adrenaline response to amphatemine.

After an initial increase in urinary catecholamines there was a gradual decrease during chronic amphetamine administration. An increased survival after otherwise lethal doses of amphetamine was observed. No evidence of an increased metabolic inactivation of amphetamine in chronically treated animals as measured by the pattern of distribution of urinary metabolites of injected d-amphetamine-3H was found.

Brain and heart noradrenaline were decreased to 70% of the control level after a single amphetamine injection (20 mg/kg). After chronic administration of amphetamine for 7 and 30 days the levels were reduced to 50% and 40% respectively. In addition, brain dopamine which increased after acute administration was depleted to about 50% of the control level in chronically amphetamine-treated rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alleva, J. J.: Metabolism of tranylcypromine-C14 and dl-amphetamine-C14 in the rat. J. med. Chem. 6, 621–624 (1963).

    Google Scholar 

  • Anagnoste, B., and M. Goldstein: The metabolism of tyramine-H3 in different regions of the CNS. Life Sci. 6, 1535–1540 (1967).

    Article  PubMed  Google Scholar 

  • Axelrod, J.: Studies on sympathomimetic amines. II. The biotransformation and physiological disposition of d-amphetamine, d-p-hydroxyamphetamine and d-methamphetamine. J. Pharmacol. exp. Ther. 214, 315–326 (1954).

    Google Scholar 

  • Beauvallet, M., J. Fugazza, and M. Legrand: Excrétion urinaire de l'adrénaline, de la noradrénaline et de la dopamine au cours des 24 heures qui suivent l'administration d'amphétamine. C. R. Soc. Biol. (Paris) 160, 546–550 (1966).

    Google Scholar 

  • Biscardi, A. M., A. Carpi, and O. A. Orsingher: Urinary excretion of catecholamines in the rat after their liberation by reserpine or dexamphetamine. Brit. J. Pharmacol. 23, 529–539 (1964).

    Google Scholar 

  • Burns, J. J., and A. H. Conney: Enzyme stimulation and inhibition in the metabolism of drugs. Proc. roy. Soc. Med. 58, 955–960 (1965).

    PubMed  Google Scholar 

  • Carlsson, A., M. Lindqvist, A. Dahlström, K. Fuxe, and D. Masuoka: Effects of the amphetamine group on intraneuronal brain amines in vivo and in vitro. J. Pharm. Pharmacol. 17, 521–524 (1965).

    PubMed  Google Scholar 

  • —, and B. Waldeck: A fluorimetric method for the determination dopamine (3-hydroxytyramine). Acta physiol. scand. 44, 293–298 (1958).

    PubMed  Google Scholar 

  • — —: β-hydroxylation of tyramine in vivo. Acta pharmacol. (Kbh.) 20, 371–374 (1964).

    Google Scholar 

  • —, K. Fuxe, B. Hamberger, and M. Lindqvist: Biochemical and histochemical studies on the effects of imipramine-like drugs and (+)-amphetamine on central and peripheral catecholamine neurons. Acta physiol. scand. 76, 481–497 (1966).

    Google Scholar 

  • Consolo, S., E. Dolfini, S. Garattini, and L. Valzelli: Desipramine and amphetamine metabolism. J. Pharm. Pharmacol. 19, 253–256 (1967).

    PubMed  Google Scholar 

  • Dingell, J. V., M. L. Owens, M. R. Norvich, and F. Sulser: On the role of norepinephrine biosynthesis in the central action of amphetamine. Life Sci. 6, 1155–1162 (1967).

    Article  PubMed  Google Scholar 

  • Dring, L. G., R. L. Smith, and R. T. Williams: The fate of amphetamine in man and other mammals. J. Pharm. Pharmacol. 18, 402–404 (1966).

    PubMed  Google Scholar 

  • Ehrich, W. E., and E. B. Krumbhaar: The effects of large doses of benzedrine sulphate on the albino rat: Functional and tissue changes. Ann. intern. Med. 10, 1874–1888 (1937).

    Google Scholar 

  • Ellison, T., L. Gutzait, and E. J. van Loon: The comparative metabolism of d-amphetamine-C14 in the rat, dog and monkey. J. Pharmacol. exp. Ther. 152, 383–387 (1966).

    PubMed  Google Scholar 

  • Euler, U. S., and F. Lishajko: Improved technique for the fluorimetric estimation of catecholamines. Acta physiol. scand. 51, 348–355 (1961).

    PubMed  Google Scholar 

  • - - Effect of directly and indirectly acting sympathomimetic amines on adrenergic transmitter granules. Acta physiol. scand. (in press) (1968).

  • Glowinski, J., and J. Axelrod: Effects of drugs on the uptake, release and metabolism of H3-norepinephrine in the rat brain. J. Pharmacol. exp. Ther. 149, 43–49 (1965).

    PubMed  Google Scholar 

  • — —, and L. L. Iversen: Regional studies of catecholamines in the rat brain. IV. Effects of drugs on the disposition and metabolism of H3-norepinephrine and H3-dopamine. J. Pharmacol. exp. Ther. 153, 30–41 (1966).

    PubMed  Google Scholar 

  • — —, and R. J. Baldessarini: Metabolism of norepinephrine in the central nervous system. Pharmacol. Rev. 18, 1201–1238 (1967).

    Google Scholar 

  • Goldstein, M., and J. E. Contrera The inhibition of norepinephrine and epinephrine synthesis in vitro. Biochem. Pharmacol. 7, 77–78 (1961).

    Article  PubMed  Google Scholar 

  • Gunne, L.-M.: Catecholamines and 5-hydroxytryptamine in morphine tolerance and withdrawal. Acta physiol. scand. 58, suppl. 204 (1963).

    Google Scholar 

  • -, and T. Lewander: Brain catecholamines during chronic amphetamine intoxication (in press) (1966).

  • — —: Long-term effects of some dependence-producing drugs on the brain monoamines. Molecular Basis of some Aspects of Mental Activity, Vol. 2, pp. 75–81 London-New York: Academic Press 1967.

    Google Scholar 

  • —, and D. J. Reis: Changes in brain catecholamines associated with electrical stimulation of amygdaloid nucleus. Life Sci. 11, 804–809 (1963).

    Article  PubMed  Google Scholar 

  • Hansson, L. C. F.: Evidence that the central action of (+)-amphetamine is mediated via catecholamines. Psychopharmacologia (Berl.) 10, 289–297 (1966).

    Google Scholar 

  • Hökfelt, B.: Noradrenalin and adrenaline in mammalian tissues. Acta physiol. scand. 25, suppl. 92 (1951).

    Google Scholar 

  • Kopin, I. J., J. E. Fischer, J. M. Musacchio, W. D. Horst, and V. K. Weise: “False neurochemical transmitters” and the mechanism of sympathetic blockade by monoamine ocidase inhibitors. J. Pharmacol. exp. Ther. 147, 186–193 (1965).

    PubMed  Google Scholar 

  • Lee, F.-L., N. Weiner, and U. Trendelenburg: The uptake of tyramine and formation of octopamine in normal and tachyphylactic rat atria. J. Pharmacol. exp. Ther. 155, 211–222 (1967).

    PubMed  Google Scholar 

  • Lewander, T.: Effects of amphetamine on urinary and tissue catecholamines in rats after inhibition of its metabolism with desmethylimipramine (DMI) (in press) (1968a).

  • - Influence of various psychoactive drugs on the metabolism of d-amphetamine in rats in vivo. Submitted for publication (1968b).

  • Maj, J., and E. Przegalinski: Disulfiram and some effects of amphetamine in mice and rats. J. Pharm. Pharmacol. 19, 341–343 (1967).

    PubMed  Google Scholar 

  • McLean, J. R., and M. McCartney: Effect of d-amphetamine on rat brain noradrenaline and serotonin. Proc. Soc. exp. Biol. (N. Y.) 107, 77–79 (1961).

    Google Scholar 

  • Quinton, R. M., and G. Halliwell: Effects of α-methyl DOPA and DOPA on the amphetamine excitatory response in reserpinized rats. Nature (Lond.) 200, 178–179 (1963).

    Google Scholar 

  • Randrup, A., and W. Jonas: Brain dopamine and the amphetamine reserpine interaction. J. Pharm. Pharmacol. 19, 483–484 (1967).

    PubMed  Google Scholar 

  • —, and I. Munkvad: Role of catecholamines in the amphetamine excitatory response. Nature (Lond.) 211, 5048 (1966).

    Google Scholar 

  • —, and J. Scheel-Krüger: Diethyldithiocarbamate and amphetamine stereotype behaviour. J. Pharm. Pharmacol. 18, 752 (1966).

    PubMed  Google Scholar 

  • Scheel-Krüger, J., and A. Randrup: Stereotype hyperactive behaviour produced by dopamine in the absence of noradrenaline. Life Sci. 6, 1389–1398 (1967).

    PubMed  Google Scholar 

  • Snedecor, G. W., and W. G. Cochran: Statistical methods. Sixth Edition. Ames, Iowa: The Iowa State University Press 1967.

    Google Scholar 

  • Sulser, F., M. L. Owens, and J. V. Dingell: On the mechanism of amphetamine potentiation by desipramine (DMI). Life Sci. 5, 2005–2010 (1967).

    Article  Google Scholar 

  • — —, M. R. Norvich, and J. V. Dingell: The relative role of storage and synthesis of brain norepinephrine in the psychomotor stimulation evoked by amphetamine or by desipramine and tetrabenazine. Psychopharmacologia (Berl.) 12, 322–332 (1968).

    Google Scholar 

  • Thoenen, H., A. Hürliman, K. F. Gey, and W. Haefely: Liberation of p-hydroxynorephedrine from cat spleen by sympathetic nerve stimulation after pretreatment with amphetamine. Life Sci. 5, 1715–1722 (1966).

    Article  PubMed  Google Scholar 

  • Tormey, J., and L. Lasagna: Relation of thyroid function to acute and chronic effects of amphetamine in the rat. J. Pharmacol. exp. Ther. 128, 201–209 (1960).

    PubMed  Google Scholar 

  • Utena, H.: Behavioural aberrations in methamphetamineintoxicated animals and chemical correlates in the brain. Progr. Brain Res., Vol. 21 B. Amsterdam: Elsevier 1966.

    Google Scholar 

  • Weissman, A., and B. K. Koe: Behavioural effects of l-α-methyltyrosine, an inhibitor of tyrosine hydroxylase. Life Sci. 4, 1037–1048 (1965).

    Article  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Tommy Lewander

    Present address: Psychiatric Research Center, Ulleråker Hospital, Uppsala 17

Authors and Affiliations

  1. Department of Physiology I, Karolinska Institutet, Stockholm 60

    Tommy Lewander

Authors
  1. Tommy Lewander
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

A preliminary report of part of this work has been presented at the XII Scandinavian Congress of Physiology, Turku, Finland, 1966, and at the 46th Annual Meeting of A.R.N.M.D., “The Addicted States”, New York, December 1966.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lewander, T. Urinary excretion and tissue levels of catecholamines during chronic amphetamine intoxication. Psychopharmacologia 13, 394–407 (1968). https://doi.org/10.1007/BF00404954

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00404954

Key-Words

Search

Navigation