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Pharmacological Implications of the Effects of Amphetamine and Its Analogs on the Turnover Rate of Tissue Catecholamines

  • E. Costa
  • M. K. Naimzada
  • A. Revuelta
Part of the Advances in Behavioral Biology book series (ABBI, volume 1)

Abstract

It is now well established that an acute paranoid psychosis may follow d-amphetamine administration (Young and Scoville 1938). Hence, Connell (1958), Bell (1965), and Kety (1967) have proposed this psychosis as a model for the study of affective disorders and schizophrenia. A better understanding of the biochemical factors involved in the actions elicited by d-amphetamine may increase the practical utility of this model. The picture that has emerged from our studies in rats on the biochemical correlates of the pharmacological effects of d-amphetamine can be summarized as follows:
  1. 1.

    d-Amphetamine depletes central and peripheral norepinephrine (NE) stores when injected in doses ten-fold greater than those required to increase exploratory motor activity (0.3 mg/kg i.V.); the doses of d-amphetamine decreasing brain NE content, however, fail to deplete striatal dopamine (DA) (Costa and Groppetti 1970a; Groppetti, Naimzada, and Costa 1971).

     
  2. 2.

    The d-amphetamine doses depleting brain NE also cause accumulation of p-hydroxynorephedrine in peripheral and central noradrenergic neurons. Since the biological half-life of p-hydroxynorephedrine concentrations in rat brain is twenty times longer than that of d-amphetamine, this metabolite persists in brain tissue longer than its parent compound (Groppetti and Costa 1969). Similar findings were independently reported by Brodie et al. (1969).

     
  3. 3.

    The persistent localization of p-hydroxynorephedrine in central and peripheral noradrenergic neurons parallels the long-lasting depletion of NE (Costa and Groppetti 1970a).

     
  4. 4.

    After a single peritoneal injection of 3 to 10 mg/kg of d-amphetamine, the pharmacological responses, including stereotype behavior and increase of locomotor activity,have disappeared 24 to 36 hours earlier than the depletion of NE. This finding suggests that the time course of the depletion of brain NE is unrelated to that of the pharmacological effects (hyperthermia, increase of motor activity, stereotype behavior, and anorexia) (Costa and Groppetti 1970b).

     

Keywords

Turnover Rate Stereotype Behavior Increase Motor Activity Biochemical Correlate Amphetamine Abuse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Bell, D. S. 1965. Comparison of amphetamine psychosis and schizophrenia. Brit. J. Psychiat. 111:701.PubMedCrossRefGoogle Scholar
  2. Boissier, J. R.; Simon, P.; Fichelle, J.; and Hervouet, E. 1965. Action psychoanalytique de quelques anorexigenes derives de 1a phénéthylamine. Therapie 20:297.PubMedGoogle Scholar
  3. Brodie, B. B.; Cho, A. K.; Stefano, P.J.E.; and Gessa, G. L. 1969. On mechanisms of NE release by amphetamine and tyramine and tolerance to their effects. In Advances in Biochemical Psychopharmacology, vol. 1. E. Costa and P. Greengard (eds.). New York: Raven Press, p. 219.Google Scholar
  4. Connell, P. H. 1958. Amphetamine psychosis. Maudsley Monographs, No. 5. London: Chapman and Hall, p. 62.Google Scholar
  5. Costa, E. 1970. Simple neuronal models to estimate turnover rate of noradrenergic transmitters in vivo. In Advances in Biochemical Psychopharmacology, vol. 2. E. Costa and E. Giacobini (eds.). New York: Raven Press, p. 169.Google Scholar
  6. Costa, E., and Groppetti, A. 1970a. Biosynthesis and storage of catecholamines in tissues of rats injected with various doses of d-amphetamine. In Amphetamines and Related Compounds; Proceedings of the Mario Negri Institute for Pharmacological Research. E. Costa and S. Garattini (eds.). New York: Raven Press, p. 231.Google Scholar
  7. Costa, E., and Groppetti, A. 1970b. Relationships between biochemical and pharmacological responses elicited by d-amphetamine. Presented at the symposium, Current Concepts on Amphetamine Abuse, Duke University, North Carolina, in press.Google Scholar
  8. Costa, E., and Neff, N. H. 1970. Estimation of turnover rates to study the metabolic regulation of the steady-state level of neuronal monoamines. In Handbook of Neurochemistry, vol. 4. A. Lajtha (ed.). New York: Plenum Publ. Co., p. 45.Google Scholar
  9. Costa, E.; Spano, P. F.; Groppetti, A.; Algeri, S.; and Neff, N. H. 1968. Simultaneous determination of tryptophan, tyrosine, catecholamines and serotonin specific activity in rat brain. Atti. Accad.Med. Lombard. 23:1100.Google Scholar
  10. Costa, E.; Groppetti, A.; and Revuelta, A. 1970. Action of fenfluramine on monoamine stores of rat tissues. Brit. J. Pharmacol., in press.Google Scholar
  11. Groppetti, A., and Costa, E. 1969. Tissue concentrations of p-hy-droxynorephedrine in rats injected with d-amphetamine: Effect of pretreatment with desipramine. Life Sci. 8:653.PubMedCrossRefGoogle Scholar
  12. Groppetti, A.; Naimzada, M. K.; and Costa, E. 1971. Evidence for a stereoisomeric effect of (+)amphetamine on the striatum dopamine turnover rate and motor activity. J. Pharmacol. Exp. Ther., submitted for publication.Google Scholar
  13. Kety, S. S. 1967. The hypothetical relationships between amines and mental illness: A critical synthesis. In Amines and Schizo-phrenia. H. E. Himwich, S. S. Kety, and J. P. Smythies (eds.). New York: Pergamon Press, p. 271.Google Scholar
  14. LeDouarec, J. C., and Neveu, C. 1970. Pharmacology and biochemistry of fenfluramine. In AmphetaminE and Related Compounds; Pro-ceedings of thz Mario Negri Institute for Pharmacological Research. E. Costa and S. Garattini (eds.). New York: Raven Press, p. 75.Google Scholar
  15. Morgan, C. D.; Cattabeni, F.; and Costa, E. 1970. Methamphetamine and their metabolites and monoamine concentrations in rat tissue. J. Pharmacol. Exp. Ther., submitted for publication.Google Scholar
  16. Oswald, I. 1970. Effects on sleep of amphetamine and its derivatives. In Amphetamines and Related Compounds; Proceedings of the Mario Negri Institute for Pharmacological Research. E. Costa and S. Garattini (eds.). New York: Raven Press, p. 865.Google Scholar
  17. Randrup, A., and Munkvad, J. 1966. Role of catecholamines in the amphetamine excitatory response. Nature 211:540.PubMedCrossRefGoogle Scholar
  18. Sanders-Bush, E., and Sulser, F. 1970. Biochemical considerations on the mode of action of p-chloroamphetamine. In Amphetamines and Related Compounds; Proceedings of the Mario Negri Institute for Pharmacological Research. E. Costa and S. Garattini (eds.). New York: Raven Press, p. 865.Google Scholar
  19. Thierry, A.-M.; Blanc, G.; and Glowinski, J. 1970. Preferential utilization of newly synthesized norepinephrine in the brain stem of stressed rats. Europ. J. Pharmacot. 10:139.CrossRefGoogle Scholar
  20. Young, D., and Scoville, W. B. 1938. Paranoid psychosis in narcolepsy and the possible danger of benzedrine treatment. Med. Clin. N. Amer. 22:637.Google Scholar

Copyright information

© Plenum Press, New York 1971

Authors and Affiliations

  • E. Costa
    • 1
  • M. K. Naimzada
    • 1
  • A. Revuelta
    • 1
  1. 1.Laboratory of Preclinical PharmacologyNational Institute of Mental Health St. Elizabeths HospitalUSA

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