Neurochemical Research

, Volume 15, Issue 9, pp 889–898 | Cite as

Effect of age and monosodium-L-glutamate (MSG) treatment on neurotransmitter content in brain regions from male fischer-344 rats

  • D. R. Wallace
  • R. DawsonJr.
Original Articles


Peripheral administration of monosodium-L-glutamate (MSG) has been found to be neurotoxic in neonatal rats. When administered in an acute, subconvulsive dose (500 mg/kg i.p.), MSG altered neurotrnnsmitter content in discrete brain regions of adult (6 month old) and aged (24 month old) male Fischer-344 rats. Norepinephrine (NE) content was reduced in both the hypothalamus (16%) and cerebellum (11%) of adult rats, but was increased in both the hypothalamus (7%) and cerebellum (14%) of aged rats after MSG treatment. MSG also altered the dopamine content in adult rats in both the posterior cortex and the striatum, causing a reduction (23%) and an increase (12%), respectively. Glycine content in the midbrain of aged rats increased (21%) after MSG injection. Of particular interest is the widespread monoamine and amino acid deficits found in the aged rats in many of the brain regions examined. NE content was decreased (11%) in the cerebellum of aged rats. Dopamine content was reduced in both the posterior cortex (35%) and striatum (10%) of aged rats compared to adult animals. Cortical serotonergic deficits were present in aged rats with reductions in both the frontal (13%) and posterior cortex (21%). Aged rats also displayed deficits in amino acids, particularly the excitatory amino acids. There were glutamate deficits (9–18% reductions) in the cortical regions (posterior and frontal) as well as midbrain and brain stem. Aspartate, the other excitatory amino acid transmitter, was reduced 10% in the brainstem of aged rats. These data indicate that an acute, subconvulsive, dose of MSG may elicit neurochemical changes in both adult and aged male Fisher-344 rats, and that there are inherent age-related deficits in particular neurotransmitters in aged male Fisher-344 rats as indicated by the reductions in both monoamines and amino acids.

Key words

Monosodium-L-glutamate aging neurotransmitters Fischer 344 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cork, L. C., Kitt, C. A., Struble, R. G., Griffin, J. W., and Price, D. L. 1987. Animal models of degenerative neurological disease. Pages 241–269,in Animal Models: Assessing the Scope of Their Use in Biomedical Research, Alan R. Liss, New York.Google Scholar
  2. 2.
    Hollander, C. F., and Mos, J. 1986. The old animal as a model in research on brain aging and Alzheimer's disease/senile dementia of the Alzheimer's type. Pages 337–343,in Swaab, D. F., Fliers, E., Mirmiran, M., Van Gool, W. A., and Van Haaren, F. (eds.), Progress in Brain Research, Vol. 70, Elsevier Science, New York.Google Scholar
  3. 3.
    Sarter, M. 1987. Measurement of cognitive abilities in senescent animals. Inter. J. Neurosci. 32:765–774.Google Scholar
  4. 4.
    Smith, G. 1988. Animal models of Alzheimer's disease: experimental cholinergic denervation. Brain Res. Rev. 13:103–118.Google Scholar
  5. 5.
    Sarter, M. 1987. Animal models of brain aging and dementia. Compr. Gerontol 1:4–15.Google Scholar
  6. 6.
    Greenamyre, J. T. 1986. The role of glutamatc in neurotransmission and in neurological disorders. Arch. Neurol. 43:1058–1063.Google Scholar
  7. 7.
    Schwarcz, R., Foster, A. C., French, E. D., Whetsell, W. O., and Kohler, C. 1984. Excitotoxic models for neurodegenerative disorders. Life Sci. 35:19–32.Google Scholar
  8. 8.
    Jhamandas, K., and Marien, M. 1987. Glutamate-evoked release of endogenous brain dopamine: inhibition by an excitatory amino acid antagonist and an enkephalin analogue. Br. J. Pharmac. 90:641–650.Google Scholar
  9. 9.
    Vezzani, A., Wu, H.-Q., and Samanin, R. 1987. [3H]Norepinephrine release from hippocampal slices is an in vitro biochemical tool for investigation of the pharmacological properties of excitatory amino acid receptors. J. Neurochem. 49:1438–1442.Google Scholar
  10. 10.
    Dawson Jr., R. 1983. Acute and long lasting neurochemical effects of monosodium glutamate administration to mice. Neuropharmacol. 22:1417–1419.Google Scholar
  11. 11.
    Nelson, M. F., Zaczek, R., and Coyle, J. T. 1980. Effects of sustained seizures produced by intrahippocampal injection of kainic acid on noradrenergic neurons: evidence for local control of norepinephrine releases. J. Pharmacol. Exp. Ther. 214:694–702.Google Scholar
  12. 12.
    Gellman, R. L., Kallianos, J. A., and McNamara, J. O. 1987. Alpha-2 receptors mediate an endogenous noradrenergic suppression of kindling development. J. Pharmacol. Exp. Ther. 241:891–898.Google Scholar
  13. 13.
    Baran, H., Sperk, G., Hortnagl, H., Sapetschnig, G., and Hornykiewicz, O. 1985. α2-adrenoceptors modulate kainic acid-induced limbic seizures. Eur. J. Pharmacol. 113:263–269.Google Scholar
  14. 14.
    Fletcher, A., and Forster, E. A. 1988. A proconvulsant action of selective α2-adrenoceptor antagonists. Eur. J. Pharmacol. 151:27–34.Google Scholar
  15. 15.
    Platt, K., Butler, L. S., Bonhaus, D. W., and McNamara, J. O. 1987. Evidence implicating alpha-2 adrenergic receptors in the anticonvulsant action on intranigral muscimol. J. Pharmacol. Exp. Ther. 241:751–754.Google Scholar
  16. 16.
    Olney, J. W. 1969. Glutamate-induced retinal degeneration in neonatal mice. Electron microscopy of the acutely evolving lesion. J. Neuropath. Exper. Neurol. 28:455–474.Google Scholar
  17. 17.
    Olney, J. W., and Sharpe, L. G. 1969. Brain lesions in an infant rhesus monkey treated with monosodium glutamate. Science 166:386–388.Google Scholar
  18. 18.
    Olney, J. W., Sharpe, L. G., and Feigin, R. D. 1972. Glutamate-induced brain damage in infant primates. J. Neuropath. Exper. Neurol. 31:464–488.Google Scholar
  19. 19.
    Dawson, Jr., R., Callahan, M. F., and Annau, Z. 1986. Hypothalamic monoamine metabolism in mice: Evaluation of drug challenges and neurotoxic insult. Pharmacol. 32:25–37.Google Scholar
  20. 20.
    Dawson, Jr., R. 1986. Developmental and sex-specific effects of low dose neonatal monosodium glutamate administration on mediobasal hypothalamic chemistry. Neuroendocrin. 42:158–166.Google Scholar
  21. 21.
    Dawson, Jr., R., and Annau, Z. 1985. Neonatal monosodium glutamate administration alters noradrenergic measures in the brainstem of the mouse. Brain Res. Bull. 15:117–121.Google Scholar
  22. 22.
    Freider, B., and Grimm, V. E. 1987. Prenatal monosodium glutamate causes long lasting cholinergic and adrenergic changes in various brain regions. J. Neurochem. 48:1359–1365.Google Scholar
  23. 23.
    Gabriel, S. M., MacGarvey, U. M., Koenig, J. I., Swartz, K. J., Martin, J. B., and Beal, M. F. 1988. Characterization of galanin-like immunoreactivity in the rat brain: effects of neonatal glutamate treatment. Neurosci. Letters. 87:114–126.Google Scholar
  24. 24.
    Magarinos, A. M., Estivariz, F., Morado, M. I., and DeNicola, A. F. 1988. Regulation at the central nervous system-pituitary-adrenal axis in rats after neonatal treatment with monosodium glutamate. Neuroendocrin. 48:105–111.Google Scholar
  25. 25.
    Nemeroff, C. B., Konkol, R. J., Bissette, G., Youngblood, W., Martin, J. B., Brazeau, P., Stone, M. S., Prange, A. J. Prange, G. R. Breese, and Kiser, J. S. 1977. Analysis at the disruption in hypothalamic-pituitary regulation in rats treated neonatally with monosodiumL-glutamate (MSG): Evidence for the involvement of tuberoinfundibular cholinergic and dopaminergic systems in neuroendocrine regulation. Endocrin. 101:613–622.Google Scholar
  26. 26.
    Rose, P. A., and Weick, R. F. 1986. Evidence for reorganization of the neuroendocrine centers regulating pulsatile LH secretion in rats receiving neontal monosodium L-glutamate treatment. J. Endocrin. 113:261–269.Google Scholar
  27. 27.
    Arauz-Contreras, J., and Feria-Velasco, A. 1984. Monosodium-L-glutamate-induced convulsions. I. Differences in seizure pattern and duration of effect as a function of age in rats. Gen. Pharmac. 15:391–395.Google Scholar
  28. 28.
    Pardridge, W. M. 1979. Regulation of amino acid availability to the brain: Selective control mechanisms for glutamate. Pages 125–137,in Flier, L. J., Garattini, S., Kare, M. R., Reynolds, W. A., and Wurtman, R. J. (eds.), Glutamic Acid: Advances in Biochemistry and Physiology, Raven Press, New York.Google Scholar
  29. 29.
    Stegnik, L. D., Reynolds, W. A., Flier, Jr., L. J., Baker, G. L., Daabees, T. T., and Pitkin, R. M. 1979. Comparative metabolism of glutamate in the mouse, monkey and man. Pages 85–102,in Flier, L. J., Garattini, S., Kare, M. R., Reynolds, W. A., and Wurtman, R. J. (eds.), Glutamic Acid: Advances in Biochemistry and Physiology, Raven Press, New York.Google Scholar
  30. 30.
    Glowinski, J., and Iverson, L. L. 1966. Regional studies of catecholamines in the rat brain. I. The disposition of [3H]NE, [3H]DA, and [3H]DOPA in various regions of the brain. J. Neurochem. 13:655–669.Google Scholar
  31. 31.
    Kontur, P., Dawson, R., and Monjan, A. A. 1984. Manipulation of mobile phase parameters for the HPLC separation of endogenous monoamines in rat brain tissue. J. Neurosci. Meth. 11:5–18.Google Scholar
  32. 32.
    Joseph, M. H., and Davies, P. 1983. Electrochemical activity of o-phthalaldehyde-mercaptoethanol derivatives of amino acids: Application to high-performance liquid chromatographic determination of amino acids in plasma and other biological materials. J. Chromat. 277:125–136.Google Scholar
  33. 33.
    Lindroth, P., and Mopper, K. 1979. High performance liquid chromatographic determination of subpicomole amounts of amino acids; by precolumn fluorescence derivatization witho-phthalaldehyde. Anal. Chem. 51:1667–1674.Google Scholar
  34. 34.
    Einarsson, S. 1985. Selective determination of secondary amino acids using precolumn derivitization with 9-fluoronylmethylchloroformate and reversed phase high-performance liquid chromatography. J. Chromat. 348:213–220.Google Scholar
  35. 35.
    Olsson, Y., Klatzo, I., and Sourander, P. 1968. Blood brain barrier to albumin in embryonic, newborn, and adult rats. Acta Neuropathol. 10:117–122.Google Scholar
  36. 36.
    Alafuzoff, I., Adolfsson, R., Bucht, G., and Winblad, B. 1983. Albumin and immunoglobulin in plasma and cerebrospinal fluid and blood-cerebrospinal fluid barrier function in patients with dementia of Alzheimer's type and multinfarct dementia. J. Neurol. Sci. 60:465–472.Google Scholar
  37. 37.
    Elovarra, I., Icen, A., Palo, J., and Erkinjuntii, T. 1985. CSF in Alzheimer's disease-studies on blood brain barrier function and intrathecal protein synthesis. J. Neurol. Sci. 70:73–80.Google Scholar
  38. 38.
    Hardy, J. A., Mann, D. M. A., Webster, P., and Winblad, B. 1986. An integrative hypothesis concerning the pathogenesis and progression of Alzheimer's disease. Neurobiol. Aging. 7:489–502.Google Scholar
  39. 39.
    Pardridge, W. M. 1977. Kinetics of competitive inhibition of neutral amino acid transport across the blood brain barrier. J. Neurochem. 28:103–108.Google Scholar
  40. 40.
    Banay-Schwartz, M., Lajtha, A., and Palkovits, M. 1989. Changes with aging in the levels of amino acids in rat CNS structural elements I. Glutamate and related amino acids. Neurochem. Res. 14:555–562.Google Scholar
  41. 41.
    Banay-Schwartz, M., Lajtha, S., and Palkovits, M. 1989. Changes with aging in the levels of amino acids in rats CNS structural elements II. Taurine and Small neutral amino acids. Neurochem. Res. 14:563–570.Google Scholar
  42. 42.
    Bigl, V., Arendt, T., Fischer, S., Fischer, S., Fischer, Werner, M., Arendt, A. 1987. The cholinergic system in aging. Geront. 33:172–180.Google Scholar
  43. 43.
    Gilad, G. M., Rabey, J. M., Tizabi, Y., and Gilad, V. H. 1987. Age-dependent loss and compensatory changes of septo-hippocampal cholinergic neurons in two rat strains differing in longevity and response to stress. Brain Res. 436:311–322.Google Scholar
  44. 44.
    Strong, R., Rehwaldt, C., and Wood, N. G. 1986. Intra-regional variations in the effect of aging on high affinity choline uptake, choline acetyltransferase and muscarinic cholinergic receptors in rat neostriatum. Exper. Geront. 21:177–186.Google Scholar
  45. 45.
    Springer, J. E., Tayrien, M. W., and Loy, R. 1987. Regional analysis of age-related changes in the cholinergic system of the hippocampal formation and basal forebrain of the rat. Brain Res. 407:180–184.Google Scholar
  46. 46.
    Lamour, Y., Dutar, P., and Jobert, A. 1987. Septo-hippocampal neurons: Altered properties in the aged rat. Brain Res. 416:277–282.Google Scholar
  47. 47.
    Bhaskaran, D., and Radha, E. 1983. Monoamine levels and monoamine oxidase activity in different regions of rat brain as a function of age. Mech. Aging Develop. 23:151–160.Google Scholar
  48. 48.
    Bickford, P. C. 1983. Age-related alterations in noradrenergic neurotransmission in Sprague-Dawley and Fischer-344 rat strains. Age. 6:100–105.Google Scholar
  49. 49.
    Pittman, R. N., Minneman, K. P., and Molinoff, P. B. 1980. Alterations in β1- and β2-adrenergic receptor density in the cerebellum of aging rats. J. Neurochem. 35:273–275.Google Scholar
  50. 50.
    Weiland, N. G., and Wise, P. M. 1986. Effects of age on β1- and β2-adrenergic receptors in the brain assessed by quantitative autoradiography. Brain Res. 398:305–312.Google Scholar
  51. 51.
    Miller, J. A., and Zahniser, N. R. 1987. Quantitative autoradiographic analysis of125I-pindolol binding in Fischer-344 rat brain: Changes in β-adrenergic receptor density with aging. Neurobiol. Aging 9:267–272.Google Scholar
  52. 52.
    Nomura, Y., Kitamura, Y., Kawai, M., and Segawa, T. 1986. α2-adrenoceptor-GTP binding regulatory protein-adenylate cyclase system in cerebral cortex membranes of adult and senescent rats. Brain Res. 379:118–124.Google Scholar
  53. 53.
    McIntosh, H. H., and Westfall, T. C. 1987. Influence of aging on catecholamine levels, accumulation and release in F-344 rats. Neurobiol. Aging 8:233–239.Google Scholar
  54. 54.
    Roubein, I. F., Embree, L. J., and Jackson, D. W. 1986. Changes in catecholamine levels in discrete regions of rat brain during aging. Exper. Aging Res. 12:193–196.Google Scholar
  55. 55.
    Estes, K. S., and Simpkins, J. W. 1980. Age-related alterations in catecholamine concentrations in discrete preoptic area and hypothalamic regions in the male rat. Brain Res. 194:556–560.Google Scholar
  56. 56.
    Estes, K. S., and Simpkins, J. W. 1984. Age related alterations in dopamine and norepinephrine activity within microdissected brain regions of ovariectomized Long-Evans rats. Brain Res. 289:209–218.Google Scholar
  57. 57.
    Simpkins, J. W. 1984. Regional changes in monoamine metabolism in the aging constant estrous rat. Neurobiol. Aging 5:309–313.Google Scholar
  58. 58.
    Petkov, V. D., Stacheva, S. L., Petkov, V. V., and Alova, L. G. 1987. Age-related changes in brain biogenic monoamines and monamine oxidase. Gen. Pharmac. 18:397–401.Google Scholar
  59. 59.
    McGreer, E. G., and McGreer, P. C. 1976. Neurotransmitter metabolism and the aging brain. Pages 389–403,in Terry, R. D., and Gershon, S. (eds). Aging Vol. 3: Raven Press, New York.Google Scholar
  60. 60.
    Carfagna, N., Trunzo, F., and Moretti, A. 1985. Brain catecholamine content and turnover in aging rats. Exper. Geront. 20:265–269.Google Scholar
  61. 61.
    Morgan, D. G., Marcusson, J. O., Nyberg, P., Webster, P., Winblad, B., Gordon, M. N., Finch, L. E. 1986. Divergent changes in D-1 and D-2 dopamine binding sites in human brain during aging. Neurobiol. Aging 8:195–201.Google Scholar
  62. 62.
    Joyce, J. N., Loeshen, S. K., Sapp, D. W., and Marshall, J. F. 1986. Age-related loss of caudate-putamen dopamine receptors revealed by quantitative autoradiography. Brain Res. 378:158–163.Google Scholar
  63. 63.
    Giorgi, O., Calderini, G., Toffano, G., and Biggio, G. 1986. D-1 dopamine receptors labelled with3H-SCH23390: Decrease in the striatum of aged rats. Neurobiol. Aging 8:51–54.Google Scholar
  64. 64.
    Carfagna, N., Trunzo, F., and Moretti, A. 1986. Brain dopamine autoreceptors in aging rats. Exper. Geront. 21:169–175.Google Scholar
  65. 65.
    Watanabe, H. 1987. Differential decrease in the rate of dopamine synthesis in several dopaminergic neurons of aged rat brain. Exper. Geront. 22:17–25.Google Scholar
  66. 66.
    Peterson, C. and Cotman, C. W. 1989. Strain-dependent decrease in glutamate binding to the N-methyl-D-aspartic acid receptor during aging. Neurosci. Lett. 104:309–313.Google Scholar
  67. 67.
    Bowen, D. M., Allen, S. J., Benton, J. S., Goodhardt, M. J., Haan, E. A., Palmer, A. M., Sims, N. R., Smith, C. C. T., Spillane, J. A., Esiri, M. M., Neary, D., Snowden, J. S., Wilcock, G. K., and Davidson, A. N. 1983. Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer's disease. J. Neurochem. 41:266–272.Google Scholar
  68. 68.
    Cross, A. J., Crow, T. J., Ferrier, I. N., and Johnson, J. A. 1986. The selectivity of the reduction of serotonergic S-2 receptors in Alzheimer's-type dimentia. Neurobiol. Aging. 7:3–7.Google Scholar
  69. 69.
    Palmer, A. M., Francis, P. T., Benton, J. S., Sims, N. R., Mann, D. M. A., Neary, D., Snowden, J. S., and Bowen, D. M. 1987. Presynaptic serotonergic dysfunction in patients with Alzheimer's disease. J. Neurochem. 48:8–15.Google Scholar
  70. 70.
    Dawson, R. Jr., Wallace, D. R., and Meldrum, M. J. 1989. Endogenous glutamate release from frontal cortex of adult and aged rats. Neurobiol. Aging. 10:665–668.Google Scholar
  71. 71.
    Dawson, R. Jr., Meldrum, M. J., and Wallace, D. R. 1989. Excitotoxin mediated neuronal loss and the regulation of excitatory amino acid release in the Aging brain. Pages 319–328,in Meyer, E. M., Simpkins J. W., Yamamoto J. (eds.), Novel Approaches for the Treatment of Alzheimer's disease, Plenum Press, New York.Google Scholar
  72. 72.
    Wallace, D. R., and Dawson Jr., R. 1989. Alteration of activity and ammonia inhibition of phosphate-activated glutaminase from aged rat brain. Soc. Neurosci. Abst. 15:307.19.Google Scholar
  73. 73.
    Bradford, H. F., Ward, H. K. and Thomas, A. J. 1978. Glutamine- a major substrate for nerve endings. J. Neurochem. 30:1453–1459.Google Scholar
  74. 74.
    Wallace, D. R., and Dawson, Jr., R. 1990. Decreased plasma taurine content in aged rats. Gerontol, (In Press).Google Scholar

Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • D. R. Wallace
    • 1
  • R. DawsonJr.
    • 1
  1. 1.Department of PharmacodynamicsUniversity of Florida, College of PharmacyGamesville

Personalised recommendations