Summary
Axotomy of the ascending monoaminergic fibers by means of a complete cerebral hemitransection stimulated the formation of dopa during 30 min after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCl, 100 mg/kg i.p., in c. striatum and the dopamine-rich part of the limbic system. Apomorphine, 0.5 mg/kg i.p., antagonized the accumulation of dopa not only on the intact but also on the lesioned side. Haloperidol, 2 mg/kg i.p., stimulated dopa accumulation on the intact side but could not further stimulate the increase in dopa caused by transection. When both drugs were given together, the inhibitory effect of apomorphine was fully counteracted by haloperidol on both sides. In the predominantly noradrenaline-innervated occipito-temporal cortex dopa formation was slightly higher on the lesioned than on the intact side and was not markedly influenced by apomorphine.
In the rest of the hemispheres the apomorphine-induced decrease in dopa formation was more pronounced on the intact than on the lesioned side and was fully antagonized by haloperidol.
The dopamine concentration was slightly higher in the lesioned c. striatum as compared to the intact side irrespective of the drugs administered. In c. striatum and the limbic system haloperidol caused a decrease in dopamine on the intact side which was not antagonized by additional treatment with apomorphine.
Hemitransection caused a decrease in noradrenaline especially in the hemisphere portion. Neither apomorphine nor haloperidol or both drugs in combination changed the latter effect.
In general, the tyrosine concentration tended to be higher on the lesioned than on the intact side in all brain structures investigated.
The data support the view that a local receptor-mediated feedback mechanism exists which is controlling dopamine synthesis even in the absence of impulse flow.
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References
Andén, N.-E.: Irritation-induced increase in the synthesis and utilization of noradrenaline following acute axotomy. Acta physiol. scand., Suppl. 440, 161 (1976)
Andén, N.-E., Roos, B.-E., Werdinius, B.: Effects of chlorpromazine, haloperidol and reserpine on the levels of phenolic acids in rabbit corpus striatum. Life Sci. 3, 149–158 (1964)
Andén, N.-E., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)
Andén, N.-E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol. 11, 303–314 (1970)
Andén, N.-E., Bédard, P., Fuxe, K., Ungerstedt, U.: Early and selective increase in brain dopamine levels after axotomy. Experientia (Basel) 28, 300–301 (1972)
Andén, N.-E., Magnusson, T., Stock, G.: Effects of drugs influencing monoamine mechanisms on the increase in brain dopamine produced by axotomy or treatment with gammahydroxybutyric acid. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 363–372 (1973)
Atack, C. V.: The determination of dopamine by a modification of the dihydroxyindole fluorimetric assay. Brit. J. Pharmacol. 48, 699–714 (1973)
Atack, C. V., Magnusson, T.: Individual elution of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from a single, strong cation exchange column, by means of mineral acid-organic solvent mixtures. J. Pharm. Pharmacol. 22, 625–627 (1970)
Bédard, P., Carlsson, A., Lindqvist, M.: Effect of a transverse cerebral hemisection on 5-hydroxytryptamine metabolism in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 272, 1–15 (1972)
Bertler, Å., Carlsson, A., Rosengren, E.: A method for the fluorimetric determination of adrenaline and noradrenaline in tissues. Acta physiol. scand. 44, 273–292 (1958)
Bunney, B. S., Walters, J. R., Roth, R. H., Aghajanian, G. K.: Dopaminergic neurons: Effect of antipsychotic drugs and amphetamine on single cell activity. J. Pharmacol. exp. Ther. 185, 560 (1973)
Carlsson, A.: Receptor-mediated control of dopamine metabolism. In: Pre- and Postsynaptic Receptors (E. Usdin and W. E. Bunney, Jr., eds.), pp. 49–65. New York: Marcel Dekker, Inc. 1975
Carlsson, A., Lindqvist, M.: Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta pharmacol. (Kbh.) 20, 140–144 (1963)
Carlsson, A., Kehr, W., Lindqvist, M., Magnusson, T., Atack, C. V.: Regulation of monoamine metabolism in the central nervous system. Pharmacol. Rev. 24, 371–384 (1972)
Carlsson, A., Kehr, W., Lindqvist, M.: Short-term control of tyrosine hydroxylase. In: Neuropsychopharmacology of Monoamines and Their Regulatory Enzymes (E. Usdin, ed.), pp. 135–142. New York: Raven Press 1974
Carlsson, A., Kehr, W., Lindqvist, M.: 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. Birkmaver and O. Hornykiewicz, eds.). Basle: Editiones Roche 1976 (in press)
Davies, O. L. (ed.): Statistical Methods in Research and Production. London: Oliver & Boyd 1949
Farnebo, L. O., Hamberger, B.: Catecholamines release and receptors in brain slices. In: Frontiers in Catecholamine Research (S. H. Snyder and E. Usdin, eds.), pp. 589–594. New York: Pergamon Press 1973
Goldstein, M., Freedman, L. S., Backstrom, T.: The inhibition of catecholamine biosynthesis by apomorphine. J. Pharm. Pharmacol. 22, 715 (1970)
Kehr, W.: Temporal changes in catecholamine synthesis of rat forebrain structures after axotomy: J. Neural Transm. 35, 307–317 (1974)
Kehr, W.: 3-Methoxytyramine as an indicator of impulse-induced dopamine release in rat brain in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 209–215 (1976)
Kehr, W.: Effect of lisuride and other ergot derivatives on monoaminergic mechanisms in rat brain. Europ. J. Pharmacol. (in press, 1977)
Kehr, W., Carlsson, A., Lindqvist, M.: A method for the determination of 3,4-dihydroxyphenylalanine (DOPA) in brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 274, 273–280 (1972a)
Kehr, W., Carlsson, A., Lindqvist, M., Magnusson, T., Atack, C.: Evidence for a receptor-mediated feedback control of striatal tyrosine hydroxylase activity. J. Pharm. Pharmacol. 24, 744–747 (1972b)
Kehr, W., Carlsson, A., Lindqvist, M.: Biochemical aspects of dopamine agonists. In: Advances in Neurology, vol. 9 (D. B. Calne, T. N. Chase, and A. Barbeau, eds.), pp. 185–195. New York: Raven Press 1975
Kehr, W., Lindqvist, M., Carlsson, A.: Distribution of dopamine in the rat cerebral cortex. J. Neural Transm. 38, 173–180 (1976)
Morgenroth, V. H., Walters, J. R., Roth, R. H.: Dopaminergic neuronsalteration in the kinetic properties of tyrosine hydroxylase after cessation of impulse flow. Biochem. Pharmacol. 25, 655–661 (1976)
Nybäck, H., Sedvall, G.: Further studies on the accumulation and disappearance of catecholamines formed from tyrosine-14C in mouse brain. Effect of some phenothiazine analogues. Europ. J. Pharmacol. 10, 193–205 (1970)
Persson, T.: Drug induced changes in 3H-catecholamine accumulation after 3H-tyrosine. Acta pharmacol. (Kbh.) 28, 378–390 (1970)
Persson, Waldeck, B.: Further studies on the possible interaction between dopamine and noradrenaline containing neurons in the brain. Europ. J. Pharmacol. 11, 315–320 (1970)
Stock, G., Magnusson, T., Andén, N.-E.: Increase in brain dopamine after axotomy or treatment with gammahydroxybutyric acid due to elimination of the nerve impulse flow. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 347–361 (1973)
Waalkes, T. P., Udenfriend, S.: A fluorimetric method for the estimation of tyrosine in plasma and tissues. J. Lab. clin. Med. 50, 733–736 (1957)
Walters, J. R., Roth, R. H.: Effect of gammahydroxybutyrate on dopamine and dopamine metabolites in the rat striatum. Biochem. Pharmacol. 21, 2111–2121 (1972)
Walters, J. R., Roth, R. H.: Dopaminergic neurons-alteration in the sensitivity of tyrosine hydroxylase to inhibition by endogeneous dopamine after cessation of impulse flow. Biochem. Pharmacol. 25, 649–654 (1976)
Zivkovic, B., Guidotti, A., Costa, E.: The regulation of the kinetic state of striatal tyrosine hydroxylase and the role of postsynaptic dopamine receptors. Brain Res. 92, 516–521 (1975)
Zivkovic, A., Guidotti, A., Costa, E.: Cyclic AMP content and regulation of tyrosine-3-mono-oxygenase in rat striatum. J. Cyclic Nucl. Res. 2, 1–10 (1976)
Zwieten-Boot, B. J. van, Noach, E. L.: The effect of blocking dopamine release on synthesis rate of dopamine in the striatum of the rat. Europ. J. Pharmacol. 33, 247–254 (1975)
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Kehr, W., Carlsson, A. & Lindqvist, M. Catecholamine synthesis in rat brain after axotomy: Interaction between apomorphine and haloperidol. Naunyn-Schmiedeberg's Arch. Pharmacol. 297, 111–117 (1977). https://doi.org/10.1007/BF00499920
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DOI: https://doi.org/10.1007/BF00499920