Skip to main content
Log in

Effects of an N-methyl-d-aspartate receptor agonist and its antagonist CPP on the levels of dopamine and serotonin metabolites in rat striatum collected in vivo by using a brain dialysis technique

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

Abstract

3-((±)-2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) is an antagonist at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. In the present study, levels of dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) were measured after intracerebroventricular injection of NMDA, CPP or both in rat striatum using a brain dialysis method. The injection of NMDA produced a significant increase in DOPAC level. HVA level was also increased by NMDA injection. The level of 5-HIAA was not affected by NMDA injection. The injection of CPP had no effect on DOPAC, HVA and 5-HIAA levels. The injection of CPP restrained the increase of DOPAC and HVA levels induced by NMDA injection. The results suggest that intracerebral injection of NMDA may increase dopamine release from rat striatum, but have no effect on serotonin release. Furthermore, CPP inhibits NMDA induced release of dopamine.

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. Watkins, J. C. 1984. Excitatory amino acids and central synaptic transmission. Trends Pharmacol. Sci. 5:373–376.

    Google Scholar 

  2. Watkins, J. C., and Evans, R. H. 1981. Excitatory amino acid transmitters. Ann. Rev. Pharmacol. Toxicol. 21:165–204.

    Google Scholar 

  3. Kita, T., Kamiya, H., and Kiyota, C. 1963. Effect of intraventricular injection of N-methylated GABA-derivatives on the central nervous system of conscious mice. Biochem. Pharmacol. 12:213–221.

    Google Scholar 

  4. Anis, N. A., Berry, S. C., Burton, N. R., and Lodge, D. 1983. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. J. Pharmacol. 79:565–575.

    Google Scholar 

  5. Flatman, J. A., Schwindt, P. C., Crill, W. E., and Stafstrom, C. E. 1983. Multiple actions of N-methyl-D-aspartate on cat neocortical neurons in vitro. Brain Res. 266:169–173.

    Google Scholar 

  6. Gean, P. W., and Shinnick-Gallagher, P. 1988. Epileptiform activity induced by magnesium-free solution in slices of rat amygdala: Antagonism by N-methyl-D-aspartate receptor antagonists. Neuropharmacology 27:557–562.

    Google Scholar 

  7. Croucher, M. J., Collins, J. F., and Meldrum, B. S. 1982. Anticonvulsant action of excitatory amino acid antagonists. Science 216:889–901.

    Google Scholar 

  8. Meldrum, B. S., Croucher, M. J., Badman, G., and Collins, J. F. 1983. Antiepileptic action of excitatory amino acid antagonists in the photosensitive baboon, Papio papio. Neurosci. Lett. 39:101–104.

    Google Scholar 

  9. Chapman, A. G., Engelsen, B., and Meldrum, B. S. 1987. 2-Amino-7-phosphonoheptanoic acid inhibits insulin-induced convulsions and striatal aspartate accumulation in rats with frontal cortical ablation. J. Neurochem. 49:121–127.

    Google Scholar 

  10. Czuczwar, S. J. and Meldrum, B., 1982. Protection against chemically induced seizures by 2-amino-7-phosphonoheptanoic acid. Eur. J. Pharmacol. 83:335–338.

    Google Scholar 

  11. Peterson, D. W., Collins, J. F., and Bradford, H. F. 1983. The kindld amygdala model of epilepsy: anticonvulsant actions of amino acid antagonists. Brain Res. 275:169–172.

    Google Scholar 

  12. Simada, M., Kabuto, H., and Yokoi, I. 1987. The effect of ω-phosphono-α-aminocarboxylic acids on seizures and brain amino acid levels in E1 mice. Research Communications in Chemical Pathology and Pharmacology 57:359–373.

    Google Scholar 

  13. Herrling, P. L., Morris, R., and Salt, T. E. 1983. Effects of excitatory amino acids and their antagonists on membrane and action potentials of cat caudate neurons. J. Physiol. 339:207–222.

    Google Scholar 

  14. Davies, J., Evans, R. H., Herrling, P. L., Jones, A. W., Olverman, H. J., Pook, P., and Watkins, J. C. 1986. CPP, a new potent and selective NMDA antagonist. Depression of central neuron responses, affinity for [3H]D-AP5 binding sites on brain membranes and anticonvulsant activity. Brain Res. 382:169–173.

    Google Scholar 

  15. Harris, E. W., Ganong, A., Monaghan, D. T., Watkins, J. C., and Cotman, C. W. 1986. Action of 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP): a new and highly potent antagonist of N-methyl-d-aspartate receptors in the hippocampus. Brain Res. 382:174–177.

    Google Scholar 

  16. Lehmann, J., Schneider, J., McPherson, S., Murphy, D. E., Bernard, P., Tsai, C., Bennett, D. A., Pastor, G., Steel, D. J., Boehm, C., Cheney, D. L., Liebman, J. M., Williams, M., and Wood, P. L. 1987. CPP, a selective N-methyl-d-aspartate (NMDA)-type receptor antagonist: characterization in vitro and in vivo. J. Pharmacol. Exp. Ther. 240:737–746.

    Google Scholar 

  17. Murphy, D. E., Schneider, J., Boehm, C., Lehmann, J., and Williams, M. 1987. Binding of [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid to rat brain membranes: a selective, high affinity ligand for N-methyl-d-aspartate receptors. J. Pharmacol. Exp. Ther. 240:778–784.

    Google Scholar 

  18. Turski, L., Klockgether, T., Sontag, K. H., Herrling, P. L., and Watkins, J. C. 1974. Muscle relaxant and anticonvulsant activity of 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, a novel N-methyl-d-aspartate antagonist, in rodents. Neurosci. Lett. 73:143–148.

    Google Scholar 

  19. Boldry, R. C., and Uretsky, N. J. 1988. The importance of dopaminergic neurotransmission in the hypermotility response produced by the administration of N-methyl-d-aspartic acid into the nucleus accumbens. Neuropharmacology 27:569–577.

    Google Scholar 

  20. Jones, S. M., Snell, L. D., and Johnson, K. M. 1987. Inhibition by phencyclidine on excitatory amino acid-stimulated release of neurotransmitter in the nucleus accumbens. Neuropharmacology 26:173–179.

    Google Scholar 

  21. Roberts, P. J., and Anderson, S. D. 1979. Stimulatory effect ofl-glutamate and related amino acids on [3H]dopamine release from rat striatum: an in vitro model for glutamate actions. J. Neurochem. 32:1539–1545.

    Google Scholar 

  22. Roberts, P. J., and Sharif, N. A. 1978. Effects ofl-glutamate and related amino acids upon the release of [3H]dopamine from rats striatal slices. Brain Res. 157:391–395.

    Google Scholar 

  23. Snell, L. D., and Johnson, K. M. 1986. Characterization of the inhibition of excitatory amino acid-induced neurotransmitter release in the rat striatum by phencyclidine-like drugs. J. Pharmacol. Exp. Ther. 238:938–946.

    Google Scholar 

  24. Baker, M. K., Jenner, P., and Marsden, C. D. 1985. Excitatory amino acid agonists and antagonists alter K+-evoked, but not basal, release of [3H]-dopamine from rat striatal slices. Br. J. Pharmac. 84:181.

    Google Scholar 

  25. Phebus, L. A., Perry, K. W., Clemens, J. A., and Fuller, R. W. 1986. Brain anoxia releases striatal dopamine in rats. Life Sci. 38:2447–2453.

    Google Scholar 

  26. Kaneyuki, T., Morimasa, T., and Shohmori, T. 1986. Changes in brain monoamine levels in cholecystokinin-induced satiety. Neurosciences 12:104–105.

    Google Scholar 

  27. Lasley, S. M., Michaelson, I. A., Greenland, R. D., and McGinnis, P. M. 1984. Simultaneous measurement of tyrosine, tryptophan and related monoamines for determination of neurotransmitter turnover in discrete rat brain regions by liquid chromatography with electrochemical detection. J. Chromatogr. 305:27–42.

    Google Scholar 

  28. Divac, I., Fonnun, F. and Storm-Mathisen, J. 1977. High-affinity uptake of glutamate in terminals of corticostriatal axons. Nature (Lond) 266:377–378.

    Google Scholar 

  29. McGeer, P. L., McGeer, E. G., Scherer, U., and Singh, K. 1977. A glutamatergic corticostriatal path?. Brain Res. 128:369–373.

    Google Scholar 

  30. Gioguieff, M. F., Kemel, M. L., and Glowinski, J. 1977. Presynaptic effect ofl-glutamic acid on the release of dopamine in the striatal slices. Neurosci. Lett. 6:73–78.

    Google Scholar 

  31. Lehmann, J. and Scatton, B. 1982. Characterization of excitatory amino acid receptor-mediated release of [3H]acetylcholine from rat striatal slices. Brain Res. 252:77–89.

    Google Scholar 

  32. Herdon, H., Strupish, J., and Nahorski, S. R. 1985. Differences between the release of radiolabelled and endogenous dopamine from superfused rat brain slices: effects of depolarizing stimuli, amphetamine and synthesis inhibition. Brain Res. 348:309–320.

    Google Scholar 

  33. McBean, G. J., and Roberts, P. J. 1981. Glutamate-preferring receptors regulate the release ofd-[3H]-aspartate from rat hippocampal slices. Nature (Lond) 291:593–594.

    Google Scholar 

  34. Wojtowicz, J. M., Gysen, M., and MacDonald, J. F. 1981. Multiple reversal potentials for responses tol-glutamic acid. Brain Re. 213:195–200.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kabuto, H., Yokoi, I., Mizukawa, K. et al. Effects of an N-methyl-d-aspartate receptor agonist and its antagonist CPP on the levels of dopamine and serotonin metabolites in rat striatum collected in vivo by using a brain dialysis technique. Neurochem Res 14, 1075–1080 (1989). https://doi.org/10.1007/BF00965613

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00965613

Key Words

Navigation