Summary
Intracerebroventricular injection of γ-aminobutyric acid (GABA) was performed in male rats and the brain monoamines, 5-hydroxyindoleacetic acid (5-HIAA), tyrosine and tryptophan levels were measured. GABA induced within 30 min a marked dose-dependent increase in the brain contents of dopamine (DA), serotonin (5-HT), tyrosine and tryptophan, while noradrenaline (NA) was lowered. Large doses of GABA, i.e. 1.5–3 mg/rat, were required for these effects. Aminooxyacetic acid (AOAA), an inhibitor of GABA-transaminase, when given alone in a dose of 25 mg/kg i.p. caused a significant rise of DA, 5-HT and tryptophan. The combination of GABA and AOAA raised these levels more than either agent alone. Picrotoxin (4 mg/kg, i.p.) a claimed GABA receptor antagonist partially counteracted the GABA-induced DA rise. Monoamine synthesis was studied in different parts of the brain by measuring the accumulated dopa and 5-hydroxytryptophan (5-HTP), 30 min after NSD 1015 (3-hydroxybenzylhydrazine HCl, 100 mg/kg) an inhibitor of aromatic L-aminoacid decarboxylase, given i.p. 5 min after GABA. GABA caused a marked rise in dopa formation both in DA-and NA-predominated brain regions. Also 5-HTP formation was enhanced. The effects on both dopa and 5-HTP formation showed marked regional differences. The data suggest that GABA, by activating specific receptors, causes inhibition of firing of dopaminergic neurones and the opposite effect on the noradrenergic neurones. The nature of the effect on 5-HT metabolism needs further investigation.
Similar content being viewed by others
References
Andén, N.-E.: Inhibition of the turnover of the brain dopamine after treatment with gammaaminobutyrate 2-oxyglutarate transaminase inhibitor aminooxyacetic acid. Naunyn-Schmiedeberg's Arch. Pharmacol. 283, 419–424 (1974)
Andén, N.-E., Stock, G.: Inhibitory effect of gammahydroxybutyric acid and gammaaminobutyric acid on the dopamine cells in the substantia nigra. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 89–92 (1973)
Atack, C. V.: The determination of dopamine by a modification of the dihydroxyindole fluorometric assay. Br. J. Pharmacol. 48, 699–714 (1973)
Atack, C., Lindqvist, M.: Conjoint vative and orthophthaldialdehyde condensate assays for the fluorimetric determination of 5-hydroxyindole in brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 267–284 (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 acidorganic 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)
Carlsson, A., Davis, J. N., Kehr, W., Lindqvist, M., Atack, C. V.: Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 153–168 (1972)
Carlsson, A., Lindqvist, M.: Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J. Pharm. Pharmacol. 25, 437–440 (1973)
Chase, T. N., Walters, J. R.: Pharmacologic approaches to the manipulation of GABA mediated synaptic function in man. In: GABA in Nervous System Function Roberts, E., Chase, T. N., Tower, O. B. (eds.), pp. 497–513. New York: Raven Press 1976
Green, A. R., Tordoff, A. F. C., Bloomfield, M. R.: Elevation of brain GABA concentrations with aminooxyacetic acid; Effect on the hyperactivity syndrome produced by increased 5-hydroxytryptamine synthesis in rats. J. Neural Transm. 39, 103–112 (1976)
Iversen, L. L.: Symposium on novel transmitter substances —Chairman's Introduction. In: Proceedings of the Sixth International Congress of Pharmacology. (Tuomisto, J., Paasonen, M. K., eds.), Vol. 2, pp. 35–38. Helsinki, 1975
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 (1972)
Okada, Y.: Role of GABA in the substantia nigra. In: GABA in Nervous System Function. Roberts, E., Chase, T. N., Tower, O. B. (eds.), pp. 235–243. New York: Raven Press 1976
Philippu, A., Przuntek, H., Roensberg, W.: Superfusion of the hypothalamus with gamma-aminobutyric acid: Effect on release of noradrenaline and blood pressure. Naunyn-Schmiedeberg's Arch. Pharmacol. 276, 103–118 (1973)
Waalkes, T. P., Udenfriend, S.: A fluorometric method for the estimation of tyrosine in plasma and tissues. J. Lab. Clin. Med. 50, 733–736 (1957)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Biswas, B., Carlsson, A. The effect of intracerebroventricularly administered GABA on brain monoamine metabolism. Naunyn-Schmiedeberg's Arch. Pharmacol. 299, 41–46 (1977). https://doi.org/10.1007/BF00508635
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00508635