Skip to main content
Log in

Chronic lithium treatment and status epilepticus induced by lithium and pilocarpine cause selective changes of amino acid concentrations in rat brain regions

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

We measured the effects of four weeks of dietary lithium treatment and of status epilepticus induced by administration of pilocarpine to lithium-treated rats on the concentrations of amino acids in four regions of rat brain: cerebral cortex, hippocampus, striatum, and substantia nigra. To ensure accurate quantitation of the amino acids, animals were sacrificed by focussed beam microwave irradiation and amino acids were measured using a fully validated triple-column ion-exchanged amino acid analyzer with post-column o-phthalaldehyde derivatization and fluorometric detection. The concentrations of four amino acids, threonine, methionine, lysine and tyrosine, were increased significantly in two to four brain regions by chronic lithium treatment. Their concentrations remained elevated, or were further increased, during status epilepticus. The concentrations of eight amino acids and ammonia were not altered by lithium treatment but increased in concentration during status epilepticus in some brain regions. Glycine, serine, arginine and citrulline were decreased by chronic lithium treatment. Status epilepticus increased the concentrations of these four amino acids above that found in the lithium-treated samples in some of the brain regions that were examined. Six amino acids and glutathione were generally unaltered by both treatments. These results are related to the effects of lithium treatment and are compared with changes reported by others following treatment with a variety of convulsive stimuli.

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

  1. Wood, A. J., and Goodwin G. M. 1987. A review of the biochemical and neuropharmacological actions of lithium. Psychol. Med. 17:579–600.

    PubMed  Google Scholar 

  2. Berrettini, W. H., Nurberger, Jr., J. I., Hare, T. A., Simmons-Alling, S. Gershon, E. S., and Post, R. M. 1983. Reduced plasma and CSF gamma-aminobutyric acid in affective illness: Effect of lithium carbonate. Biol. Psychiat. 18:185–194.

    PubMed  Google Scholar 

  3. Marcus, S. R., Naidger, H. A., Chandrakala, M. V., Rao, T. I., and Sadasivudu, B. 1986. Acute and short-term effects of lithium on glutamate metabolism in rat brain. Biochem. Pharmacol. 35:365–369.

    PubMed  Google Scholar 

  4. Miller, J. M., Ferraro, T. N., Jope, R. S., Snead, O. C. and Hare, T. A. 1988. The effect of sacrifice by decapitation or microwave irradiation on rat brain anmino acids. Soc. Neurosci. Abstr. 14:348.

    Google Scholar 

  5. Jope, R. S. 1979. Effects of lithium treatmentin vitro andin vivo on acetycholine metabolism in rat brain. J. Neurochem. 33:487–495.

    PubMed  Google Scholar 

  6. Honchar, M. P., Olney, J. W., and Sherman, W. R. 1983. Systemic cholinergic agents induce seizures and brain damage in lithium-treated rats. Science 220:323–325.

    PubMed  Google Scholar 

  7. Jope, R. S., Morrisett, R. A., and Snead, O. C. 1986. Characterization of lithium potentiation of pilocarpine-induced status epilepticus in rats. Exp. Neurol. 91:471–480.

    PubMed  Google Scholar 

  8. Morrisett, R. A., Jope, R. S., and Snead, O. C. 1987. Status epilepticus is produced by administration of cholinergic agonists to lithium-treated rats: Comparison with kainic acid. Exp. Neurol. 98:594–605.

    PubMed  Google Scholar 

  9. Clifford, D. B., Olney, J. W., Maniotis, A., Collins, R. C. and Zorumski, C. F. 1987. The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. Neurosci. 23:953–968.

    Google Scholar 

  10. Jope, R. S. 1987. Lithium potentiates brain cholinergic activity: Studies of seizures. Pages 781–788in: M. J. Dowdall and J. N. Hawthorne (eds.) Cellular and Molecular Basis of Cholinergic Function, Ellis Horwood LTD., England.

    Google Scholar 

  11. Jope, R. S., and Morrisett, R. A. 1986. Neurochemical comsequences of status epilepticus induced in rats by coadministration of lithium and pilocarpine. Exp. Neurol. 93:404–414.

    PubMed  Google Scholar 

  12. Jope, R. S., Simonato, M. and Lally, K. 1987. Acetylcholine content in rat brain is elevated by status epilepticus induced by lithium and pilocarpine. J. Neurochem. 49:944–951.

    PubMed  Google Scholar 

  13. Ferraro, T. N., and Hare, T. A. 1984. Triple-column ion-exchange physiological amino acid analysis with fluorescent detection: Baseline characterization of human cerebrospinal fluid. Anal. Biochem. 143:82–94.

    PubMed  Google Scholar 

  14. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.

    PubMed  Google Scholar 

  15. Tagliamonte, A., Tagliamonte, P., Perez-Cruet, J., and Gessa, G. L. 1971 Increase of brain tryptophan caused by drugs which stimulate serotonin synthesis. Nature New Biol. 229:125–126.

    PubMed  Google Scholar 

  16. Schubert, J. 1973. Effect of chronic lithium treatment on monoamine metabolism in rat brain. Psychopharmacol. 32:301–311.

    Google Scholar 

  17. Berggren, U. 1985. Effects of chronic lithium treatment of brain monoamine metabolism and amphetamine-induced locomotor stimulation in rats. J. Neural. Transmission 64:239–250.

    Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  20. Ahuwalia, P., Grewaal, D. S., and Singhal, R. L. 1981. Brain GABAergic and dopaminergic systems following lithium treatment and withdrawal. Prog. Neuropsychopharmacol. 5:527–530.

    PubMed  Google Scholar 

  21. Banay-Schwartz, M., Wajda, I. J., Manigault, I., DeGuzman, T., and Lajtha, A. 1982. Lithium: Effect on [3H]spiperone binding, ionic content, and amino acid levels in the brain of rats. Neurochem. Res. 7:179–189.

    PubMed  Google Scholar 

  22. Pasquini, J. S., Salomone, J. R., and Gomez, C. J. 1968. Amino acid changes in themouse brain during audiogenic seizures and recovery. Exp. Neurol. 21:245–256.

    PubMed  Google Scholar 

  23. Whisler, K. E., Tews, J. K., and Stone, W. E. 1968. Cerebral amino acids and lipids in drug-induced status epilepiticus. J. Neurochem. 15:215–220.

    PubMed  Google Scholar 

  24. Chapman, A. G., Meldrum, B. S., and Siesjo, B. K. 1977. Cerebral metabolic changes during prolonged epileptic seizures in rats. J. Neurochem. 28:1025–1035.

    PubMed  Google Scholar 

  25. Chapman, A. G., Westerberg, E., Premachandra, M., and Meldrum, B. S. 1984. Changes in regional neurotransmitter amino acid levels in rat brain during seizures induced by L-allylglycine, bicuculline, and kainic acid. J. Neurochem. 43:62–70.

    PubMed  Google Scholar 

  26. Chapman, A. G., Cheetham, S. C., Hart, G. P., Meldrum, B. S., and Westerberg, E. 1985. Effects of two convulsant β-carboline derivatives, DMCM and β-CCM, on regional neurotransmitter amino acid levels and on in vitro D-[3H]aspartate release in rodents. J. Neurochem. 45:370–381.

    PubMed  Google Scholar 

  27. Blennow, G., Folbergrova, J., Nilsson, B., and Siesjo, B. K. 1979. Cerebral metabolic and circulatory changes in the rat during sustained seizures induced by DL-homocysteine. Brain Res. 179:129–146.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jope, R.S., Miller, J.M., Ferraro, T.N. et al. Chronic lithium treatment and status epilepticus induced by lithium and pilocarpine cause selective changes of amino acid concentrations in rat brain regions. Neurochem Res 14, 829–834 (1989). https://doi.org/10.1007/BF00964811

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00964811

Key Words

Navigation