Effect of Reserpine on Monoamine Synthesis and on Apparent Dopaminergic Receptor Sensitivity in Rat Brain



There seems to be general agreement that the monoamine-depleting action of reserpine is due to blockade of the uptake mechanisms located in the intracellular storage organelles, generally called “granules” or “synaptic vesicles” (see Carlsson, 1965). Although the monoamine-synthesizing enzymes are not primarily involved, several secondary actions on the activities of these enzymes have been demonstrated or proposed. Dopamine-β-hydroxylase is located in the storage granules, and the blocking action of reserpine on their uptake mechanism may lead to reduced availability of the substrate dopamine (Rutledge and Weiner, 1967). As to the first steps in the synthesis of monoamines, i.e., the hydroxylation of tyrosine and tryptophan, the action of reserpine on the storage mechanism appears to cause rather complex secondary changes in the activity of the enzymes involved. Sustained increases in 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid levels in brain after reserpine treatment, outlasting the initial phase of monoamine net release, may indicate increased rates of monoamine synthesis, even though alternative explanations cannot be excluded (Andén et al, 1963, 1964).


Tyrosine Hydroxylase Tryptophan Hydroxylase Brain Part Tryptophan Level Tyrosine Hydroxylase Activity 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Andén, N.-E., and Henning, M., 1966, Adrenergic nerve function, noradrenaline level and noradrenaline uptake in cat nictitating membrane after reserpine treatment, Acta Physiol. Scand. 67:498.PubMedCrossRefGoogle Scholar
  2. Andén, N.-E., Roos. B.-E., and Werdinius, B., 1963, 3, 4-Dihydroxyphenylacetic acid in rabbit corpus striatum normally and after reserpine treatment, Life Sci. 2:319.CrossRefGoogle Scholar
  3. Andén, N.-E., Roos, B.-E., and Werdinius, B., 1964, Effects of chlorpromazine, haloperidol and reserpine on the levels of phenolic acids in rabbit corpus striatum, Life Sci. 3:149.CrossRefGoogle Scholar
  4. Atack, C., and Lindqvist, M., 1973, Conjoint native and orthophthaldialdehyde-condensate assays for the fluorimetric determination of 5-hydroxyindoles in brain, Naunyn-Schmiedebergs Arch. Pharmakol. 279:267.CrossRefGoogle Scholar
  5. Bédard, P., Carlsson, A., and Lindqvist, M., 1972, Effect of a transverse cerebral hemisection on 5-hydroxytryptamine metabolism in the rat brain, Naunyn-Schmiedeb ergs Arch. Pharmakol. 272:1.CrossRefGoogle Scholar
  6. Carlsson, A., 1965, Drugs which block the storage of 5-hydroxytryptamine and related amines, in: Handbuch der experimentellen Pharmakologie, Vol. XíX (V. Erspamer, ed.), pp. 529–592, Springer-Verlag, Berlin and Heidelberg.Google Scholar
  7. Carlsson, A., 1975, Receptor-mediated control of dopamine metabolism, in: Pre-and Postsyn-aptic Receptors (E. Usdin and W. E. Bunney, eds.), pp. 49–65, Marcel Dekker, New York.Google Scholar
  8. Carlsson, A., and Lindqvist, M., 1972, The effect of L-tryptophan and some psychotropic drugs on the formation of 5-hydroxytryptophan in the mouse brain in vivo, J. Neural Transm. 33:23.PubMedCrossRefGoogle Scholar
  9. Carlsson, A., and Lindqvist, M., 1973, Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo, J. Pharm. Pharmacol. 25:431.CrossRefGoogle Scholar
  10. Carlsson, A., Davis, J. N., Kehr, W., Lindqvist, M., and Atack, C. V., 1972, Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase, Naunyn-Schmiedebergs Arch. Pharmakol. 275:153.CrossRefGoogle Scholar
  11. Carlsson, A., Kehr, W., and Lindqvist, M., 1976, Agonist-antagonist interaction on dopamine receptors in brain, as reflected in the rates of tyrosine and tryptophan hydroxylation, in: Advances in Parkinsonism: Biochemistry, Physiology, Treatment (W. Birkmayer and O. Hornykiewicz, eds.), Editiones Roche, Basle, pp. 71–81.Google Scholar
  12. Grabowska, M., Michaluk, J., and Antkiewicz, L., 1973, Possible involvement of brain serotonin in apomorphine-induced hypothermia, Eur. J. Pharmacol. 23:82.PubMedCrossRefGoogle Scholar
  13. Jequier, E., Robinson, D. S., Lovenberg, W., and Sjöerdsma, A., 1969, Further studies on tryptophan hydroxylase in rat brainstem and beef pineal, Biochem. Pharmacol. 18:1071.PubMedCrossRefGoogle Scholar
  14. Kehr, W., Carlsson, A., and Lindqvist, M., 1972, A method for the determination of 3,4-dihydroxyphenylalanine (DOPA) in brain, Naunyn-Schmiedebergs Arch. Pharmakol. 274:273.CrossRefGoogle Scholar
  15. Kehr, W., Carlsson, A., and Lindqvist, M., 1975, Biochemical aspects of dopamine agonists, in: Advances in Neurology, Vol. 9 (D. B. Calne, T. N. Chase, and A. Barbeau, eds.), pp. 185–195, Raven Press, New York.Google Scholar
  16. Mueller, R. A., Thoenen, H., and Axelrod, J., 1969, Increase in tyrosine hydroxylase activity after reserpine administration, J. Pharmacol. Exp. Ther. 169:74.PubMedGoogle Scholar
  17. Rutledge, C. O., and Weiner, N., 1967, The effect of reserpine on the synthesis of norepinephrine in the isolated rabbit heart, J. Pharmacol. Exp. Ther. 157:290.PubMedGoogle Scholar
  18. Svensson, T. H., Bunney, B. S., and Aghajanian, G. K., 1975, Inhibition of both noradrenergic and serotonergic neurons in brain by the α-adrenergic agonist clonidine, Brain Res. 92:291.PubMedCrossRefGoogle Scholar
  19. Thoenen, H., Mueller, R. A., and Axelrod, J., 1969, Trans-synaptic induction of adrenal tyrosine hydroxylase, J. Pharmacol. Exp. Ther. 169:249.PubMedGoogle Scholar
  20. Tozer, T. N., Neff, N. H., and Brodie, B. B., 1966, Application of steady state kinetics to the synthesis rate and turnover time of serotonin in the brain of normal and reserpine-treated rats, J. Pharmacol. Exp. Ther. 153:177.Google Scholar
  21. Ungerstedt, U., 1971, Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system, Acta physiol. Scand. Suppl. 367:69.PubMedGoogle Scholar
  22. Waalkes, T. P., and Udenfriend, S., 1957, A fluorometric method for the estimation of tyrosine in plasma and tissues, J. Lab. Clin. Med. 50:733.PubMedGoogle Scholar
  23. Weiner, N., Cloutier, G., Bjur, R., and Pfeffer, R. I., 1972, Modification of norepinephrine synthesis in intact tissue by drugs and during short-term adrenergic nerve stimulation, Pharmacol. Rev. 24:203.PubMedGoogle Scholar
  24. Winer, B. J., 1962, Statistical Principles in Experimental Design, McGraw-Hill Book Co., New York.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  1. 1.Department of PharmacologyUniversity of GöteborgGöteborg 33Sweden

Personalised recommendations