Skip to main content
Log in

Alterations in monoamine levels in discrete regions of rat brain after chronic administration of carbamazepine

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

Abstract

Carbamazepine (25 mg/kg body weight) was administered intraperitoneally to adult male Wistar rats for 45 days and norepinephrine (NE), dopamine (DA) and serotonin (5-HT) levels were simultaneously assayed in discrete brain regions by high performance liquid chromatographic (HPLC) method. Experimental rats displayed no behavioral abnormalities. Body and brain weights were not significantly different from control group of rats. After exposure it was observed that norepinephrine levels were elevated in motor cortex (P<0.01) and cerebellum (P<0.05), while dopamine levels were decreased in these two regions (P<0.001, P<0.05). However, dopamine levels were increased in hippocampus (P<0.01). Serotonin levels were significantly decreased in motor cortex (P<0.001) and hypothalamus (P<0.001) but increased in striatum-accumbens (P<0.001) and brainstem (P<0.001). These results suggest that carbamazepine may mediate its anticonvulsant effect by differential alterations of monoamine levels in discrete brain regions particularly in motor cortex and cerebellum.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Simonsen, J., Zander Olsen, P., Kuhl, V., Lund, M., and Wendelboe, J. 1976. A comparative controlled study between carbamazepine and diphenyl hydantoin in psychomotor epilepsy. Epilepsia 17:169–176.

    PubMed  Google Scholar 

  2. Troupin, A., Ojemann, L. M., Halpern, L., Dodrill, C., Wilkur, R., Friel, P., and Feigl, P. 1977. Carbamazepine — A double blind comparison with phenytoin. Neurology 27:511–519.

    PubMed  Google Scholar 

  3. McLean, M. J., Taylor, C. P., and Macdonald, R. L. 1984. Phenytoin and carbamazepine limit sustained high frequency repetitive firing of action potentials of hippocampal neurons in cell culture and tissue slices. Soc. Neurosci. Abst. 10:873.

    Google Scholar 

  4. McLean, M. J., and Macdonald, R. L. 1986. Carbamazepine and 10, 11-epoxy carbamazepine produce use and voltage dependent limitation of rapidly firing action potentials of mouse central neurons in cell culture. J. Pharmacol. Exp. Therap. 228:727–738.

    Google Scholar 

  5. Jullien, R. M., and Hollister, R. P. 1975. Carbamazepine: Mechanism of action. Adv. Neurol. 11:263–277.

    PubMed  Google Scholar 

  6. Rasmussen, P., and Rushede, J. 1970. Facial pain treated with carbamazepine Tegretol. Acta Neurol. Scand. 46:385–408.

    PubMed  Google Scholar 

  7. Hernandez-Peon, R. 1964. Anticonvulsant action of G 32883. Third Proc. Int. Neuropsychopharmacologicum 3:303–311.

    Google Scholar 

  8. Skeritt, J. H., Davies, L. P., and Johnston, G. A. R. 1983. Interactions of the anticonvulsant carbamazepine with adenosine receptors; Neurochemical studies. Epilepsia 24:642–643.

    Google Scholar 

  9. Marangos, P. J., Post R. M., Patel, J., Zander, K., Parma, A., and Weiss, S. 1983. Specific and potent interactions of carbamazepine with brain adenosine receptors. Eur. J. Pharmacol. 93:175–182.

    PubMed  Google Scholar 

  10. Schlichter, W., Bristow, M. F., and Schultz, R. S. 1986. Seizures occuring during intensive chlorpromazine therapy. Can. Med. Assoc. J. 74:364–366.

    Google Scholar 

  11. Azzaro, A. J., Wenger, G. R., Craig, C. R., and Stitzel, R. E. 1972. Reserpine induced alterations in brain amines and their relationship to changes in the incidence of minimal electro-shock seizures in mice. J. Pharmacol. Exp. Ther. 180:558–568.

    PubMed  Google Scholar 

  12. Kilian, M., and Frey, H. H. 1973. Central monoamines and convulsive thresholds in mice and rats. Neuropharmacology 12:681–692.

    PubMed  Google Scholar 

  13. Mohr, E., and Corcoran, M. E. 1981. Depletion of noradrenaline and amygdaloid kindling. Exp. Neurol. 72:507–511.

    PubMed  Google Scholar 

  14. Hiramatsu, M., Fujimoto, N., and Mori, A. 1982. Catecholamine level in cerebrospinal fluid of epileptics. Neurochem. Res. 7:157–171.

    Google Scholar 

  15. Mori, A., Hiramatsu, M., Namba, S., Nishimoto, A., Ohnoto, J., Mayanagi, Y., and Sakura, T. 1987. Decreased dopamine levels in the epileptic focus. Res. Commun. Chem. Pathol. Pharmacol. 56:157–164.

    PubMed  Google Scholar 

  16. Pintor, M., Pocotte, S., and Mefford, I. 1988. Indoles, catechols and tyrosine hydroxylase in the human epileptic cortex. Soc. Neurosci. Abstr. 14:1032.

    Google Scholar 

  17. Wada, J. A., Balzamo, E., Meldrum, B. S., and Naquet, R. 1972. Behavioral and electrographic effects ofl-5-hydroxytryptophan andD,L-para-chlorophenylalanine in epileptic Senegalese baboon Papio papio. Electroencephalogr. Clin. Neurophysiol. 3:520–526.

    Google Scholar 

  18. Meldrum, B. S., Turski, L., Schwarz, M., Cruezuar, S. J., Sontag, K. H. 1986. Anticonvulsant action of 1, 3-dimethyl 5-aminoadamantane: pharmacological studies in rodents and baboon, Papio papio. Naunyn. Schmiedebergs. Arch. Pharmacol. 332:93–97.

    PubMed  Google Scholar 

  19. Westerink, B. H. C., Lejeune, B., Korf, J., and Van Pragg, H. M. 1977. On the significance of regional dopamine metabolism in the rat brain for the classification of centrally acting drugs. Eur. J. Pharmacol. 42:179–190.

    PubMed  Google Scholar 

  20. Quattrone, A., Crunelli, V., and Samanin, R. 1978. Seizure Susceptibility and anticonvulsant activity of carbamazepine, diphenyl hydantoin and phenobarbital in rats with selective depletion of brain monamines. Neuropharmacology 17:643–647.

    PubMed  Google Scholar 

  21. Purdy, R. E., Julien, R. M., Fairhurst, A. S., and Terry, M. D. 1977. Effect of carbamazepine on in vitro uptake and release or norepinephrine in adrenergic nerves of rabbit aorta and in whole brain synaptosomes. Epilepsia 18:251–257.

    PubMed  Google Scholar 

  22. Quattrone, A., Annunziato, L., Aguglia, U., and Preziosi, P. 1981. Carbamazepine, phenytoin and phenobarbitone do not influence brain catecholamine uptake, invivo in male rats. Arch. Int. Pharmacodyn. Ther. 252:180–185.

    PubMed  Google Scholar 

  23. Lindgren, S., Anden, N. E., and Anden, M. G. 1982. A flourometric method for determination of GABA in tissues following cation exchange chromatography and condensation with O-phthalaldehyde. J. Neural. Transm. 55:243–252.

    Google Scholar 

  24. Murai, S., Saito, H., Masuda, Y., and Itoh, T. 1988. Rapid determination of norepinephrine, dopamine, serotonin, their precursor aminoacids and related metabolites in discrete brain areas of mice within ten minutes by HPLC with electrochemical detection. J. Neurochem. 50:473–479.

    PubMed  Google Scholar 

  25. Farhali-Hassan, Assael, B. M., Bossi, L., Garathini, S., Gerna, M., Gomeni, R., and Morselli, P. L. 1976. Carbamazepine pharmacokinetics in young adult and pregnant rats. Relation to pharmacological effects. Arch. Int. Pharmacodyn. Ther. 220:125–139.

    PubMed  Google Scholar 

  26. Quattrone, A., and Samanin, R. 1977. Decreased anticonvulsant activity of carbamazepine in 6-hydroxy dopamine treated rats. Eur. J. Pharmacol. 41:333–336.

    Google Scholar 

  27. Waldmeier, P. C., Baumann, P. A., Fehr, B., De Herdt, P., and Maitre, L. 1984. Carbamazepine decreases catecholamine turnover in the rat brain. J. Pharmacol. Exp. Ther. 231:166–172.

    PubMed  Google Scholar 

  28. Trottier, S., Berger, B., Chauvel, P., Dedek, J., and Gay, M. 1981. Alterations of the cortical noradrenergic system in chronic cobalt epileptogenic foci in the rat: A histoflourescent and biochemical study. Neuroscience 6:1069–1080.

    PubMed  Google Scholar 

  29. Altamura, A. C., Bonati, M., Brunello, N., Giordano, P. L., and Algeri, S. 1987. The activities of some neurotransmitter synthesizing enzymes in experimental cobalt epilepsy. Neurosci Lett 7:83–87.

    Google Scholar 

  30. Reimann, W., Zumstein, A., Jackish, R., Starke, K., and Hertting, G. 1979. Effect of extracellular dopamine on the release of dopamine in the rabbit caudate nucleus: Evidence for a dopaminergic feedback inhibition. Naunyn. Schmiedberg. Arch. Pharmacol. 306:53–60.

    Google Scholar 

  31. Goldstein, D., Nadi, N. S., Stull, R., Wyler, A. R., and Porter, R. J. 1988. Levels of catechols in normal and epileptic regions of the human brain. J. Neurochem. 50:225–229.

    PubMed  Google Scholar 

  32. Papeschi, R., Moline-Negro, P., Sourkes, T. L., and Giuseppe, E. 1972. The concentration of homovanillic acid and 5-hydroxy indole acetic acids in ventricular and lumbar cerebrospinal fluid. Neurology 22:1151–1159.

    PubMed  Google Scholar 

  33. Devinsky, O., Emoto, S., Goldstein, D. S., Stull, R., Porter, R. J., Theodore, W. H., and Nadi, N. S. 1992. Cerebrospinal fluid and serum levels of dopa, catechols and monoamine metabolites in patients with epilepsy. Epilepsia 33:263–270.

    PubMed  Google Scholar 

  34. Crunelli, V., Bernasconi, S., and Samanin, R. 1979. Evidence against serotonin involvement in the tonic component of electrically induced convulsions and in carbamazepine anticonvulsant activity. Psychopharmacology 66:79–85.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meshki Baf, M.H., Subhash, M.N., Lakshmana, K.M. et al. Alterations in monoamine levels in discrete regions of rat brain after chronic administration of carbamazepine. Neurochem Res 19, 1139–1143 (1994). https://doi.org/10.1007/BF00965147

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00965147

Key Words

Navigation