Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Effect of lithium and other alkali metals on brain chemistry and behavior

I. Glutamic acid and GABA in brain regions

  • 38 Accesses

  • 20 Citations


Glutamic acid and GABA concentrations were measured in brain areas of rats injected with the chloride salts of Li+, Na+, K+, Rb+ or Cs+ for 5 days. Regional changes in brain glutamic acid and GABA were found in animals after lithium, rubidium or cesium, but not potassium, compared to sodium treatments. Increased glutamic acid and GABA levels, caused by lithium and rubidium, were found in brain structures (hypothalamus and amygdala) known to be involved in emotional behavior. Whether these changes are associated with the effective use of lithium and, perhaps, of rubidium in affective disorders remains obscure.

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


  1. Baxter, C. F.: The nature of γ-aminobutyric acid. In: Handbook of neurochemistry, Vol. 3, A. Lajtha, ed., pp. 289–353. New York: Plenum Press 1970

  2. Baruk, H., Fabiani, P.: Study of blood ammonia in periodic psychosis and in the epileptic state. Ann. med.-psychol. 120, 721–726 (1962)

  3. Benesová, O., Simáne, Z., Kunz, K.: Pyruvate, α-ketoglutarate and gamma-aminobutyrate in brains of rats with different levels of excitability. Physiol. Behav. 2, 203–205 (1967)

  4. Bhattacharya, G.: Influence of Li+ on glucose metabolism in rats and rabbits. Biochim. biophys. Acta (Amst.) 93, 644–646 (1964)

  5. Bond, P. A.: The uptake of γ-[3H]aminobutyric acid by slices from various regions of rat brain and the effect of lithium. J. Neurochem. 20, 511–517 (1973)

  6. Cade, J. F. J.: Lithium salts in the treatment of psychotic excitement. Med. J. Aust. 36, 349–352 (1949)

  7. DeFeudis, F. V., Delgado, J. M. R.: Effects of lithium on amino acids in mouse brain in vivo. Nature (Lond.) 225, 749–750 (1970)

  8. Edelson, A., Gottesfeld, Z., Samuel, D., Yuwiler, A.: Effect of lithium and other alkali metals on brain chemistry and behavior. II. Intracranial self-stimulation behavior. Psychopharmacologia (Berl.) 45, 233–237 (1976)

  9. Fieve, R. R., Meltzer, H., Dunner, D. L., Levitt, M., Mendlewicz, J., Thomas, A.: Rubidium: Biochemical, behavioral and metabolic studies in humans. Amer. J. Psychiat. 130, 55–61 (1973)

  10. Gaitonde, M. K., Dahl, D. R., Elliott, K. A. C.: Entry of glucose carbon into amino acids of rat brain and liver in vivo after injection of uniformly 14C-labelled glucose. Biochem. J. 94, 345–352 (1965)

  11. Gottesfeld, Z., Ebstein, B. S., Samuel, D.: Effect of lithium on concentrations of glutamate and GABA levels in amygdala and hypothalamus of rat. Nature, New Biol. 234, 124–125 (1971)

  12. Gottesfeld, Z., Samuel, D., Icekson, I.: Glutamate and GABA levels and glutamate decarboxylase activity in brain regions of rats after prolonged treatment with alkali cations. Experientia (Basel) 29, 68–69 (1973)

  13. Hazard, R., Boissier, J. R., Mouillé, P., Bréteau, M.: Actions hyperglycémiantes des ions potassium, rubidium et cesium comparées à leurs actions hypertensives. C.R. Soc. Biol. (Paris) 161, 2159–2161 (1967)

  14. Ho, A. K. S., Gershon, S., Pinckney, L.: The effects of acute and prolonged lithium treatment on the distribution of electrolytes, potassium and sodium. Arch. int. Pharmacodyn. 186, 54–65 (1970)

  15. Jasper, H. H., Khan, R. T., Elliott, K. A. C.: Amino acids release from the cerebral cortex in relation to its state of activation. Science 147, 1448–1449 (1965)

  16. Katz, R. I., Chase, T. N., Kopin, I. J.: Effect of ions on stimulus-induced release of amino acids from mammalian brain slices. J. Neurochem. 16, 961–967 (1969)

  17. Katzman, R., Pappius, H. M.: Brain electrolytes and fluid metabolism. Baltimore: Williams and Wilkins 1973

  18. Krnjević, K. K.: Glutamate and γ-aminobutyric acid in brain. Nature (Lond.) 228, 119–124 (1970)

  19. Rees, J. R.: Lithium and γ-aminobutyrate metabolism. Life Sci. 11, part II, 925–928 (1972)

  20. Relman, A. S., Roy, A. M., Schwartz, W. B.: The acidifying effect of rubidium in normal and potassium-deficient alkalotic rats. J. clin. Invest. 34, 538–544 (1955)

  21. Schildkraut, J. J.: The catecholamine hypothesis of affective disorders: A review of supporting evidence. Amer. J. Psychiat. 122, 509–522 (1965)

  22. Schou, M.: Biology and pharmacology of the lithium ion. Pharmacol. Rev. 9, 17–58 (1957)

  23. Shopsin, B., Stern, S., Gershon, S.: Altered carbohydrate metabolism during treatment with lithium carbonate. (Absence of diagnostic specificity in hospitalized psychiatric patients.) Arch. gen. Psychiat. 26, 566–571 (1972)

  24. Shopsin, B., Wilk, S., Sathanathan, G., Gershon, S., Davis, K.: Catecholamines and affective disorders revised: A critical assessment. J. nerv. ment. Dis. 158, 369–383 (1974)

  25. Snodgrass, S. R., Hedley-Whyte, E. T., Lorenzo, A. V.: GABA transport by nerve ending fractions of cat brain. J. Neurochem. 20, 771–782 (1973)

  26. Strasberg, P., Elliott, K. A. C.: Further studies on the binding of γ-aminobutyric acid by brain. Canad. J. Biochem. 45, 1795–1807 (1967)

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Gottesfeld, Z. Effect of lithium and other alkali metals on brain chemistry and behavior. Psychopharmacologia 45, 239–242 (1976).

Download citation

Key words

  • Lithium
  • Rubidium
  • Alkali metals
  • GABA
  • Glutamic acid
  • Brain areas
  • Affective disorders