Skip to main content
SpringerLink
Log in

Changes in brain putrescine concentration associated with nonconvulsant behavioral patterns induced by systemicN-methyl-d-aspartate injection

  • Original Articles
  • Published:
Molecular and Chemical Neuropathology

Abstract

The relationship between the behavioral effects and motor activity induced byN-methyl-d-aspartate (NMDA) (150 mg/kg, ip) and brain polyamine concentration was studied in male Wistar rats. Motor activity was evaluated by an automated subtraction analysis system to measure the duration and vigor of any kind of movement. The behavioral modifications exhibited by the nonconvulsant NMDA-treated rats were evaluated according to the composition and sequence of behavioral components as: hypoactivity (pattern A), partially stereotyped activity (pattern B), and generalized stereotyped activity (pattern C). The concentration of polyamines in the frontal cortex and hippocampus was measured 8 and 24 h after drug injection. A relationship was found between the concentration of putrescine in both regions and the motor activity. In addition, the concentrations of putrescine also correlated with the vigor of the movements performed. Moreover, the putrescine concentration in the frontal cortex and hippocampus paralleled the behavioral patterns. The histological examination of the frontocortical and hippocampal areas did not reveal any evidence of damage. In conclusion, partially or generalized stereotyped activity elicited by systemic NMDA administration induces an increase in putrescine in the brain not linked to histological damage.

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

Access this article

Log in via an institution

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

  • Arai A., Baudry M., Staubli U., Lynch G., and Gall C. (1990) Induction of ornithine decarboxylase by subseizure stimulation in the hippocampus in vivo.Mol. Brain Res. 7, 167–169.

    Article  PubMed  CAS  Google Scholar 

  • Baudry M. and Najm I. (1994) Kainate-induced seizure activity stimulates the polyamine interconversion pathway in rat brain.Neurosci. Lett. 171, 151–154.

    Article  PubMed  CAS  Google Scholar 

  • Bondy S. C. and Walker C. H. (1986) Polyamines contribute to calcium-stimulated release of aspartate from brain particulate fraction.Brain Res. 371, 96–100.

    Article  PubMed  CAS  Google Scholar 

  • Bondy S. C., Mitchell C. L., Rahmaan S., and Mason G. (1987) Regional variation in the response of cerebral ornithine decarboxylase to electroconvulsive shock.Neurochem. Pathol. 7, 129–141.

    PubMed  CAS  Google Scholar 

  • Camón L., de Vera N., Vives P. and Martinez E. (1995) Putrescine as a biochemical marker of excitotoxicity in the rat brain.Amino Acids 9, 62.

    Google Scholar 

  • Chu P. J., Shirahata A., Samejima K., Saito H., and Abe K. (1994)N-(3-aminopropyl)-cyclohexylamine blocks facilitation by spermidine ofN-methyl-Dl-aspartate-induced seizure in mice in vivo.Eur. J. Pharmacol 256, 155–160.

    Article  PubMed  CAS  Google Scholar 

  • Cotman C. W., Monaghan D. T., Ottersen O. P., and Storm-Mathisen, J. (1987) Anatomical organization of excitatory amino acid receptors and their pathways.Trends Neurosci. 10, 273–280.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • de Vera N., Artigas F., Serratosa J., and Martinez E. (1991) Changes in polyamine levels in rat brain after systemic kainic acid administration: relationship to convulsant activity and brain damage.J. Neurochem. 57, 1–8.

    Article  PubMed  Google Scholar 

  • Dienel G. A. and Cruz N. F. (1984) Induction of brain ornithine decarboxylase during recovery from metabolic, mechanical, thermal, or chemical injury.J. Neurochem. 42, 1053–1061.

    Article  PubMed  CAS  Google Scholar 

  • Engstrom F. L. and Woodbury D. M. (1988) Seizure susceptibility in DBA and C57 mice: the effects of various convulsants.Epilepsia,29, 389–395.

    Article  PubMed  CAS  Google Scholar 

  • France C. P., Lu Y., Woods J. H. (1990) Interactions betweenN-methyl-d-aspartate and CGS 19755 administered intramuscularly and intracerebroventricularly in pigeons.J. Pharmacol. Exp. Ther. 255, 1271–1277.

    PubMed  CAS  Google Scholar 

  • Gilad G. M., Casero R. A., Busto R., Globus M. Y. T. (1993) Polyamines in rat brain extracellular space after ischemia.Mol. Chem. Neuropathol. 18, 27–33.

    PubMed  CAS  Google Scholar 

  • Giménez-Llort L., de Vera N., and Martinez E. Behavioral effects and motor activity induced by NMDA systemically administered in rats, submitted a.

  • Giménez-Llort L., de Vera N., and Martinez E. Qualitative and quantitative methods for motor analysis of chemically-induced behavioral responses in rats, submitted b.

  • Hayashi Y., Hattori Y., Moriwaki A., Saeki K., and Hori Y. (1989) Changes in polyamine concentrations in amigdaloid-kindled rats.J. Neurochem. 53, 986–988.

    Article  PubMed  CAS  Google Scholar 

  • Hayashi Y., Hattori Y., and Hori Y. (1992) Involvement of putrescine in the development of kindled seizure in rats.J. Neurochem. 58, 562–566.

    Article  PubMed  CAS  Google Scholar 

  • Hayashi Y., Hattori Y., Moriwaki A., Lu Y. F., and Hori Y. (1993) Increases in brain polyamine concentrations in chemical kindling and single convulsion induced by pentylenetetrazol in rats.Neurosci. Lett. 149, 63–66.

    Article  PubMed  CAS  Google Scholar 

  • Iqbal Z. and Koenig H. (1985) Polyamines appear to be second messengers in mediating Ca++ fluxes and neurotransmitter release in potassium-depolarized synaptosomes.Biochem. Biophys. Res. Commun. 133, 563–573.

    Article  PubMed  CAS  Google Scholar 

  • Koenig H., Goldstone A. D., and Lu C. Y. (1989) Polyamines mediate the reversible opening of the blood-brain barrier by the intracarotid infusion of hyperosmolal mammitol.Brain Res. 483, 110–116.

    Article  PubMed  CAS  Google Scholar 

  • Leander J. D., Lawson R. R., Ornstein P. L., and Zimmerman D. M. (1988) N-methyl-D-aspartic acid-induced lethality in mice: selective antagonism by phencyclidine-like drugs.Brain Res. 448, 115–120.

    Article  PubMed  CAS  Google Scholar 

  • Martinez E., de Vera N., and Artigas F. (1991) Differential response of rat brain polyamines to convulsant agents.Life Sci. 48, 77–84.

    Article  PubMed  CAS  Google Scholar 

  • McGurk J. F., Bennett M. V. L., and Zunin R. S. (1990) Polyamines potentiate responses of N-methyl-d-aspartate receptors expressed inXenopus oocytes.Proc. Natl. Acad. Sci. USA 87, 9971–9974.

    Article  PubMed  CAS  Google Scholar 

  • Mialon P., Cann-Moisan C., Barthélémy L., Caroff J., Joanny P., and Steinberg J. (1993) Effect of one hyperbaric oxygen-induced convulsion on cortical polyamine content in two strains of mice.Neurosci. Lett. 160, 1–3.

    Article  PubMed  CAS  Google Scholar 

  • Pajunen A. E. I., Hietala O. A., Virransalo E. L., and Piha R. S. (1978) Ornithine decarboxylase and adenosylmethionine decarboxylase in mouse brain-effect of electrical stimulationJ. Neurochem. 30, 281–283.

    Article  PubMed  CAS  Google Scholar 

  • Paschen W., Bengtsson F., Röhn G., Bonnekoh P., Siesjö B. and Hossman K. A. (1991) Cerebral polyamine metabolism in reversible hypoglycemia of rat: relationship to energy metabolites and calcium.J. Neurochem. 57, 204–215.

    Article  PubMed  CAS  Google Scholar 

  • Paschen W., Widman R. and Weber C. (1992) Changes in regional polyamine profiles in rat brain after transient cerebral ischemia (single versus repetitive ischemia): evidence for release of polyamines from injured neurons.Neurosci. Lett. 135, 121–124.

    Article  PubMed  CAS  Google Scholar 

  • Pegg A. E. and McCann P. P. (1988) Polyamine metabolism and function in mammalian cells and protozoans.ISI Atlas of Sci. (Biochem.) 11–18.

  • Porcella A., Carter C., Fage D., Voltz C., Lloyd K. G., Serrano A., and Scatton B. (1991) The effects ofN-methyl-d-aspartate and kainate lesions of the rat striatum on striatal ornithine decarboxylase activity and polyamine levels.Brain Res. 549, 205–212.

    Article  PubMed  CAS  Google Scholar 

  • Raigorodosky G. and Urca G. (1990) Spinal antinociceptive effects of excitatory amino acids antagonists: quisqualate modulates the action ofN-methyl-d-aspartate.Eur. J. Pharmacol. 182, 37–47.

    Article  Google Scholar 

  • Ransom R. W. and Stec N. L. (1988) Cooperative modulation of [3H]MK-801 binding to theN-methyl-d-aspartate recepton-ion channel complex byl-glutamate, glycine, and polyamines.J. Neurochem. 51, 830–836.

    Article  PubMed  CAS  Google Scholar 

  • Rock D. M. and MacDonald R. L. (1995) Polyamine regulation ofN-methyl-d-aspartate receptor channels.Annu. Rev. Pharmacol. Toxicol. 35, 463–482.

    Article  PubMed  CAS  Google Scholar 

  • Sakurada T., Manome Y., Tan-No K, Sakurada S., and Kisara K. (1990) The effects of substance P analogues on the scratching, biting and licking response induced by intratecal injection of N-methyl-D-aspartate in mice.Br. J. Pharmacol. 101, 307–310.

    PubMed  CAS  Google Scholar 

  • Scatton B. (1993) The NMDA receptor complex.Fundam. Clin. Pharmacol. 7, 389–400.

    Article  PubMed  CAS  Google Scholar 

  • Singh L., Oles R., and Woodruff G. (1990) In vivo interaction of a polyamine with the NMDA receptor.Eur. J. Pharmacol. 180, 391,392.

    Article  PubMed  CAS  Google Scholar 

  • Soltis R. P. and DiMicco J A. (1992) Hypothalamic excitatory amino acid receptors mediate stress-induced tachycardia in rats.Am. J. Physiol. 262, R689-R697.

    PubMed  CAS  Google Scholar 

  • Trout J. J., Koenig H., Goldstone A. D., Iqbal Z., Lu C. Y., and Siddiqui F. (1993)N-Methyl-d-aspartate receptor excitotoxicity involves activation of polyamine synthesis: protection by α-difluoromethylornithine.J. Neurochem. 60, 352–355.

    Article  PubMed  CAS  Google Scholar 

  • Zini I., Zoli M., Grimaldi R., Merlo Pich E., Biagini G., Fuxe K., and Agnati L. F. (1990) Evidence for a role of neosynthetized putrescine in the increase of glial fibrillary acidic protein immunoreactivity induced by a mechanical lesion in the rat brain.Neurosci. Lett. 120, 13–16.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), CSIC, Spain

    Lluïsa Camon & Núria de Vera

  2. Department of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), CSIC, Spain

    Lidia Giménez-Llort & Emili Martínez

Authors
  1. Lidia Giménez-Llort
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emili Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lluïsa Camon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Núria de Vera
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giménez-Llort, L., Martínez, E., Camon, L. et al. Changes in brain putrescine concentration associated with nonconvulsant behavioral patterns induced by systemicN-methyl-d-aspartate injection. Molecular and Chemical Neuropathology 30, 289–302 (1997). https://doi.org/10.1007/BF02815104

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02815104

Index Entries

Search

Navigation