Skip to main content
Log in

The effects of amfonelic acid on 5-HT metabolism in rat brain

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

The non-amphetamine stimulant amfonelic acid (AFA), an inhibitor of dopamine (DA) uptake, has been found to increase the levels of tryptophan (TRYP) and 5-hydroxyindoleacetic acid (5-HIAA) in the rat c. striatum, cerebral cortex, and brain stem. Pretreatment with the DA antagonist haloperidol did not affect this action of AFA in the c. striatum, suggesting that it is independent of the effects of this compound on DA neurons.

The duration of action of the effect of AFA on TRYP and 5-HIAA appeared to be longer than that of the increase of the striatal DA metabolites homovanillic acid and 3,4-dihydroxyphenylacetic acid.

The increased 5-HIAA concentrations seemed only in part be due to a probenecid-like effect of AFA; evidence for an increased 5-HT synthesis, probably related to the increased TRYP concentrations, was also obtained.

This biochemical effect of AFA seems to differ from those reported in the literature on amphetamine and other, related stimulating agents. It might be of interest to see whether corresponding behavioural differences between AFA and these agents can be found.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Anden, N. E., Corrodi, H., Fuxe, K., Meek, J. L.: Hallucinogenic phenylethyl-amines: interactions with serotonin turnover and receptors. Eur. J. Pharmacol.25, 176–184 (1974).

    Google Scholar 

  • Bakhit, C., Gibb, J. W.: Methamphetamine-induced depression of tryptophan hydroxylase: recovery following acute treatment. Eur. J. Pharmacol.76, 229–233 (1981).

    Google Scholar 

  • Bakhit, C., Morgan, M. E., Peat, M. A., Gibb, J. W.: Long-term effects of methamphetamine on the synthesis and metabolism of 5-hydroxytrypt-amine in various regions of the rat brain. Neuropharmacology20, 1135–1140 (1981).

    Google Scholar 

  • Bizzi, A., Bonaccorsi, A., Jespersen, S., Jori, A., Garattini, S.: Pharmacological studies on amphetamine and fenfluramine. In: Amphetamines and related compounds (Costa, E., Garattini, S., ed.), pp. 577–595. New York: Raven Press. 1970.

    Google Scholar 

  • Brase, D. A., Loh, H. H.: The increase in brain tryptophan caused by amphetamine-like drugs: correlation with an increase in body temperature. Life Sci.18, 115–122 (1976).

    Google Scholar 

  • Carlsson, A., Corrodi, H., Fuxe, K., Hökfelt, T.: Effects of antidepressant drugs on the depletion of intraneuronal brain 5-hydroxytryptamine stores caused by 4-methyl-alpha-ethyl-methyl-tyramine. Eur. J. Pharmacol.5, 357–366 (1969).

    Google Scholar 

  • Carlsson, A., Lindqvist, M.:In vivo measurements of tryptophan and tyrosine hydroxylase activities in mouse brain. J. Neural Transm.34, 79–91 (1973).

    Google Scholar 

  • Corrodi, H., Fuxe, K., Hökfelt, T.: A possible role played by central mono-amine neurones in thermoregulation. Acta Physiol. Scand.71, 224–232 (1967).

    Google Scholar 

  • Costa, E., Neff, N. H.: Estimation of turnover rates to study the metabolic regulation of the steady-state level of neuronal monoamines. In: Handbook of Neurochemistry, Vol. 4 (Lajtha, A., ed.), pp. 45–90. New York-London: Plenum Press. 1970.

    Google Scholar 

  • Curzon, G., Green, A. R.: Rapid method for the determination of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in small regions of rat brain. Brit. J. Pharmacol.39, 653–655 (1970).

    Google Scholar 

  • Fuller, R. W., Perry, K. W.: Amfonelic acid antagonism of dopamine and norepinephrine depletion byα-methyl-m-tyrosine in rat brain. Biochem. Pharmacol.30, 2025–2026 (1981).

    Google Scholar 

  • Knapp, S., Mandell, A. J., Geyer, M. A.: Effects of amphetamines on regional tryptophan hydroxylase activity and synaptosomal conversion of tryptophan to 5-hydroxytryptamine in rat brain. J. Pharmacol. exp. Ther.189, 676–689 (1974).

    Google Scholar 

  • Peters, D. A., Hrdina, P. D., Singhal, R. L., Ling, G. M.: The role of brain serotonin in DDT-induced hyperpyrexia. J. Neurochem.19, 1131–1136 (1972).

    Google Scholar 

  • Rastogi, R. B., Singhal, R. L.: Brain 5-hydroxytryptamine metabolism: adaptive changes after long-term administration of psychotropic drugs. Gen. Pharmac.9, 307–314 (1978).

    Google Scholar 

  • Reid, W. D.: Turnover rate of brain 5-hydroxytryptamine increased by d-amphetamine. Brit. J. Pharmacol.40, 483–491 (1970).

    Google Scholar 

  • Reid, W. D., Volicer, L., Smookler, H., Beaven, A., Brodie, B. B.: Brain amines and temperature regulation. Pharmacology1, 329–344 (1968).

    Google Scholar 

  • Ross, S. B., Kelder, D.: Inhibition of3H-dopamine accumulation in reserpinized and normal rat striatum. Acta Pharmacol. Tox.44, 329–335 (1979).

    Google Scholar 

  • Scheel-Krueger, J., Hasselager, E.: Studies of various amphetamines, apomorphine and clonidine on body temperature and brain 5-hydroxytryptamine metabolism in rats. Psychopharmacologia36, 189–202 (1974).

    Google Scholar 

  • Schubert, J., Sedvall, G.: Effect of amphetamines on tryptophan concentrations in mice and rats. J. Pharm. Pharmacol.24, 53–62 (1972).

    Google Scholar 

  • Schubert, J., Fyroe, B., Nybaeck, H., Sedvall, G.: Effect of cocaine and amphetamine on the metabolism of tryptophan and 5-hydroxytrypt-amine in mouse brainin vivo. J. Pharm. Pharmacol.22, 860–862 (1970).

    Google Scholar 

  • Sloviter, R. S., Drust, E. G., Connor, J. D.: Evidence that serotonin mediates some behavioral effects of amphetamine. J. Pharmacol. Exp. Ther.206, 348–352 (1978).

    Google Scholar 

  • Steranka, L. R.: Long-term decreases in striatal dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid after a single injection of amphetamine in iprindole-treated rats: time course and time-dependent interactions with amfonelic acid. Brain Res.234, 123–136 (1982).

    Google Scholar 

  • Tagliamonte, A., Tagliamonte, P., Perez-Cruet, J., Stern, S., Gessa, G. L.: Effect of psychotropic drugs on tryptophan concentration in the rat brain. J. Pharmacol. exp. Ther.177, 475–480 (1971).

    Google Scholar 

  • Trulson, M. E., Jacobs, B. L.: Long-term amphetamine treatment decreases brain serotonin metabolism: implications for theories of schizophrenia. Science205, 1295–1297 (1979).

    Google Scholar 

  • Trulson, M. E., Jacobs, B. L.: Chronic amphetamine administration decreases brain tryptophan hydroxylase activity in cats. Life Sci.26, 329–335 (1980).

    Google Scholar 

  • Weiss, B. L., Aghajanian, G. K.: Activation of brain serotonin metabolism by heat: role of midbrain raphe neurons. Brain Res.26, 37–48 (1971).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Waldmeier, P.C., Buchle, AM., Stoecklin, K. et al. The effects of amfonelic acid on 5-HT metabolism in rat brain. J. Neural Transmission 57, 149–165 (1983). https://doi.org/10.1007/BF01245115

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01245115

Keywords

Navigation