Abstract
This study was designed to investigate the effects of intracerebral injections of glutamic acid on acquisition and extinction of a bar-press response, performance of that response, and behavioral activity. Nineteen food-deprived rats bearing chronic ventricular cannulae were tested in operant conditioning chambers or in an open field. Just prior to each testing session each animal was injected intraventricularly with 10 μl of either normal or acidified saline solution (control groups), or 10 μl of 100 mMol glutamic acid solution. Acquisition of the bar-pressing response by the glutamic acid group was significantly retarded as compared to the control groups, and the responding of the glutamic acid group was suppressed during the beginning of the first few sessions of testing on a fixedinterval schedule and during extinction. Other behavioral measures, such as operant level, performance of the response on a continuous schedule, performance on fixed-interval and extinction schedules except during the start of the first few sessions, and behavioral activity, were either unaffected or only slightly affected. It is concluded that interference with the normal neurophysiological activity of glutamic acid in the central nervous system interferes with learning and suppresses behavioral output in certain situations.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Albert, K. E., Warden, C. J.: The level of performance in the white rat. Science 100, 476 (1944)
Araujo, P. E., Mayer, J.: Activity increase associated with obesity induced by monosodium glutamate in mice. Amer. J. Physiol. 225, 764–765 (1973)
Balazs, R., Machiyama, Y., Patel, A. J.: Compartmentation and the metabolism of gamma-aminobutyrate. In: Metabolic compartmentation in the brain. R. Balazs and J. E. Cremer, eds., pp. 57–70. New York: Wiley 1972
Berl, S.: Glutamate compartmentation in developing cat brain. In: Metabolic compartmentation in the brain, R. Balazs and J. E. Cremer, eds., pp. 73–79. New York: Wiley 1972a
Berl, S.: Biochemical consequences of compartmentation of glutamate and associated metabolites. In: Metabolic compartmentation in the brain, R. Balazs and J. E. Cremer, eds., pp. 3–17. New York: Wiley 1972b
Berl, S., Clarke, D. D.: Compartmentation of amino acid metabolism. In: Handbook of neurochemistry, A. Lajtha, ed., pp. 447–472. New York-London: Plenum Press 1969
Berry, H. K., Butcher, R. E., Elliot, L. A., Brunner, R. L.: The effect of monosodium glutamate on the early biochemical and behavioral development of the rat. Develop. Psychobiol. 7, 165–173 (1974)
Bhagavan, H. N., Coursin, D. B., Stewart, C. N.: Monosodium glutamate induces convulsive disorders in rats. Nature (Lond.) 232, 275–276 (1971)
Bures, J., Buresova, O., Krivanek, J.: Some metabolic aspects of Leao's spreading cortical depression. In: Structure and function of the cerebral cortex, D. B. Tower and J. P. Schade, eds., pp. 257–265. Amsterdam: Elsevier 1959
Curtis, D. R., Johnston, G. A.: Amino acid transmitters in the mammalian central nervous system. Ergebn. Physiol. 69, 97–188 (1974)
Curtis, D. R., Watkins, J. C.: The excitation and depression of spinal neurones by structurally related amino acids. J. Neurochem. 6, 117–141 (1960a)
Curtis, D. R., Watkins, J. C.: Investigations upon the possible synaptic transmitter function of gamma-aminobutyric acid and naturally occurring amino acids. In: Inhibition in the nervous system and gamma-aminobutyric acid, pp. 424–444. New York: Pergamon Press 1960b
Delgado, J. M. R., DeFeudis, F. V., Bellido, I.: Injections of GABA and glutamate into the amygdalae of awake monkeys. Commun. Behav. Biol 5, 347–357 (1971)
Desi, I., Farkas, I., Sos, J., Balogh, A.: Neurophysiological effects of glutamic acid ethylester. Acta physiol. Acad. Sci. hung. 32, 323–335 (1967)
Do Carmo, R. J., Leao, A. A. P.: On the relation of glutamic acid and some allied components to cortical spreading depression. Brain Res. 39, 515–518 (1972)
Estes, W. K.: The problem of inference from curves based on group data. Psychol. Bull. 53, 134–140 (1956)
Fifkova, E., Van Harreveld, A.: Glutamate and spreading depression. J. Neurobiol. 5, 469–473 (1974)
Van Harreveld, A., Fifkova, E.: Involvement of glutamate in memory formation. Brain Res. 81, 455–467 (1974)
Himwich, H. E., Himwich, W. A.: The permeability of the blood-brain barrier to glutamic acid in the developing rat. In: Biochemistry of the developing nervous system, H. Waelsh, ed., pp. 202–207. New York: Academic Press 1955
Hirsch, W., Mex, A., Vogel, F.: Metabolic traits in mentally retarded children as compared with normal populations: Monoaminodicarboxylic acids and their half amides and total amino acids. J. ment. Defic. Res. 13, 130–142 (1969)
Hughes, K. R., Zubek, J. P.: Effect of glutamic acid on the learning ability of bright and dull rats: I. Administration during infancy. Canad. J. Psychol. 10, 132–138 (1956)
Jasper, H. H., Khan, R. T., Elliott, K. A. C.: Amino Acids released from cerebral cortex in relation to its state of activation. Science 147, 1448–1449 (1965)
Johnston, G. A. R.: Convulsions induced in 10-day-old rats by intraperitoneal injection of monosodium glutamate and related excitant amino acids. Biochem. Pharmacol. 22, 137–140 (1973)
Krnjevic, K.: Chemical nature of synaptic transmission in vertebrates. Physiol. Rev. 54, 418–540 (1974)
Krnjevic, K., Phillis, J. W.: Iontophoretic studies of neurones in the mammalian cerebral cortex. J. Physiol. (Lond.) 165, 274–304 (1963)
Mao, C. C., Guidotti, A., Costa, E.: The regulation of cyclic guanosine monophosphate in rat cerebellum: Possible involvement of putative amino acid neurotransmitters. Brain Res. 79, 510–514 (1974)
Matsui, S., Yamamoto, C.: Release of radioactive glutamic acid from thin sections of Guinea pig olfactory cortex in vitro. J. Neurochem. 24, 245–250 (1975)
Olney, J. W.: Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 164, 719–721 (1969)
Olney, J. W.: Toxic effects of glutamate and related amino acids on the developing central nervous system. In: Heritable disorders of amino acid metabolism, W. L. Nyhan, ed., pp. 501–512. New York: Wiley 1974
Olney, J. W., Ho, O. L., Rhee, V.: Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system. Exp. Brain Res. 14, 61–76 (1971)
Phillips, H. J.: Activity of rats on free, normal, and excess glutamic acid diets. Fed. Proc. 13, 112 (1954)
Pradhan, S. N., Lynch, J. F.: Behavioral changes in adult rats treated with monosodium glutamate in the neonatal stage. Arch. int. Pharmacodyn. 197, 301–304 (1972)
Schainker, B., Olney, J. W.: Glutamate-type hypothalamic-pituitary syndrome in mice treated with aspartate or cysteate in infancy. J. Neural Trans. 35, 207–215 (1974)
Stewart, C. N., Coursin, D. B., Bhagavan, H. N.: Electroencephalographic study of l-glutamate induced seizures in rats. Toxicol. appl. Pharmacol. 23, 635–639 (1972)
Tadokoro, S., Higuchi, Y., Kuribara, H., Okuizumi, K.: Behavioral suppression induced by oral administration of monosodium l-glutamate. Pharmacol. Biochem. Behav. 2, 619–625 (1974)
Verplanck, W. S.: Unaware of where's awareness: Some verbal operants—notates, monents, and notants. In: Behavior and awareness, C. W. Eriksen, ed., pp. 130–158. Durham, N. C.: Duke Univ. Press 1962
Waelsch, H.: In vivo compartments of glutamic acid metabolism in brain and liven. In: Amino acid pools, J. T. Holden, ed., pp. 471–485. Amsterdam-London-New York: Elsevier Publishing Comp. 1962
Weinreich, D., Hammerschlag, R.: Nerve impulse-enhanced release of amino acids from non-synaptic regions of peripheral and central nerve trunks of bullfrog. Brain Res. 84, 137–142 (1975)
Weiss, L. R., Reilly, J. F., Williams, J., Krop, S.: Effects of prolonged monosodium glutamate and other high-salt diets on arterial pressure and learning ability in rats. Toxicol. appl. Pharmacol. 19, 389 (1971)
Wheeler, D. D., Boyarsky, L. L., Brooks, W. H.: The release of amino acids from nerve during stimulation. J. cell. Physiol. 67, 141–147 (1966)
Wincze, J. P., Vogel, W.: The effects of glutamic acid upon operant conditioning in rats. J. gen. Psychol. 115, 97–105 (1969)
Zimmerman, F. T., Ross, S.: Effect of glutamic acid and other amino acids on maze learning in the white rat. Arch. Neurol. Psychiat. (Chic.) 51, 446–451 (1944)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Freed, W.J., Michaelis, E.K. Effects of intraventricular glutamic acid on the acquisition, performance, and extinction of an operant response, and on general activity. Psychopharmacology 50, 293–299 (1976). https://doi.org/10.1007/BF00426847
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00426847