Abstract
PERSISTENT neuronal plasticity, including that observed at some hippocampal synapses, requires N-methyl-D-aspartate (NMDA)-mediated transmission. NMDA receptor activation may be necessary for hippocampus-dependent learning as antagonists block acquisition in many such tasks. The behavioural effects of NMDA agonists are less well defined. We have shown that a monoclonal antibody (B6B21) displaced [3H]-glycine that was bound specifically to the NMDA receptor, and enhanced the opening of its integral cation channel in a glycine-like fashion, effects that were competitively antagonized by 7-chlorokynurenic acid1. B6B21 also enhanced long-term potentiation in hippocampal slices1. We report here that intraventricular infusions of B6B21 significantly enhances acquisition rates in hippocampus-dependent trace eye blink conditioning in rabbits, halving the number of trials required to reach a criterion of 80% conditioned responses. Peripheral injections of D-cycloserine, a partial agonist of the glycine site on the NMDA receptor which crosses the blood–brain barrier, also doubles rabbits' learning rates. Pseudoconditioning control experiments indicated a lack of nonspecific behavioural sensitization effects. Our data suggest that enhanced activation of the glycine coagonist site on the NMDA receptor/channel complex facilitates one form of associative learning and may be used in other learning tasks.
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Haring, R., Stanton, P., Scheideler, M. & Moskal, J. J. Neurochem. 57, 323–332 (1991).
Patel, J., Zinkland, W. C., Thompson, C., Keith, R. & Salama, A. J. Neurochem. 54, 849–854 (1990).
Moyer, J. R. Jr, Deyo, R. A. & Disterhoft, J. F. Behavl Neurosci. 104, 243–252 (1990).
Monaghan, D. T. & Cotman, C. W. J. Neurosci. 5, 2909–2919 (1985).
Collingridge, G. L., Kehl, S. J. & McLennan, H. J. Physiol, Lond. 334, 33–46 (1983).
Oliver, M. W., Kessler, M., Larson, J., Schottler, F. & Lynch, G. Synapse 5, 265–270 (1990).
Thomson, A. M., Walker, V. E. & Flynn, D. M. Nature 338, 422–424 (1989).
Andersen, P. & Hvalby, Ø. in Excitatory Amino Acids (eds Meldrum, B. S., Moroni, F., Simon, R. P. & Woods, J. H.) 463–4 4 (Raven, New York, 1991).
Morris, R. G. M., Anderson, E., Lynch, G. S. & Baudry, M. Nature 319, 774–776 (1986).
Robinson, G. S., Crooks, G. B., Shinkman, P. G. & Gallagher, M. Psychobiology 17, 156–164 (1989).
Contreras, P. C. Neuropharmacology 29, 291–293 (1990).
Napier, R., MacRae, M. & Kehoe, E. J. exp. Psychol, Anim. Behav. Processes 18, 182–192 (1992).
Hood, W. F., Compton, R. P. & Monahan, J. B. Neurosci. Lett. 98, 91–95 (1989).
Hanngren, H., Hansson, E. & Ullberg, S. Antibiotics Chemother. 12, 46–54 (1961).
Monahan, J. B., Corpus, V. M., Hood, W. F., Thomas, J. W. & Compton, R. P. J. Neurochem 53, 370–375 (1989).
Watson, G. B., Bolanowski, M. A., Baganoff, M. P., Deppeler, C. L. & Lanthorn, T. H. Brain Res. 510, 158–160 (1990).
Golub, E. S. Immunology: A Synthesis (Sinauer, Sunderland, MA, 1987).
Vartanian, M. G. & Taylor, C. P. Neurosci. Lett. 133, 109–112 (1991).
Monahan, J. B., Handelmann, G. E., Hood, W. F. & Cordi, A. A. Pharmac. biochem. Behav. 34, 649–653 (1989).
Schwartz, B. L., Hashtroudi, S., Herting, R. L., Handerson, H. & Deutsch, S. I. Neurology 41, 1341–1343 (1991).
Thiels, E., Weisz, D. J. & Berger, T. W. Neuroscience 46, 501–509 (1992).
Disterhoft, J. F., Coulter, D. A. & Alkon, D. L. Proc. natn. Acad. Sci. U.S.A. 83, 2733–2737 (1986).
de Jonge, M. C., Black, J., Deyo, R. A. & Disterhoft, J. F. Expl Brain Res. 80, 456–462 (1990).
Solomon, P. R., van der Schaaf, E. V., Thompson, R. F. & Weisz, D. J. Behavl Neurosci. 100, 729–744 (1986).
Gaffan, D. & Gaffan, E. A. Brain 114, 2611–2618 (1991).
Squire, L. Memory and Brain (Oxford, Univ. Press, London, 1987).
Dedrick, R. L. & Flessner, M. F. in Immunity to Cancer II (ed. Mitchell, M. S.) 429–438 (Liss, New York, 1989).
Winter, G. & Milstein, C. Nature 349, 293–299 (1991).
Saragovi, H. U. et al. Science 253, 792–795 (1991).
Woodruff-Pak, D. S. & Thompson, R. F. Psychol. Aging 3, 219–229 (1988).
Solomon, P. R., Levine, E., Bein, T. & Pendlebury, W. W. Neurobiol. Aging 12, 283–287 (1991).
Miyoshi, R., Kito, S., Doudou, N. & Nomoto, T. Synapse 6, 338–343 (1990).
Foster, A. C., Willis, C. L. & Tridgett, R. Eur. J. Neurosci. 2, 270–277 (1990).
Procter, A. W., Stirling, J. M., Stratmann, G. C., Cross, A. J. & Bowen, D. M. Neurosci. Lett. 101, 62–66 (1989).
Moskal, J. R. & Schaffner, A. E. J. Neurosci. 6, 2045–2063 (1986).
Deyo, R. A., Straube, K. & Disterhoft, J. F. Science 243, 809–811 (1989).
Berger, T. W., Rinaldi, P. C., Weisz, D. J. & Thomspon, R. F. J. Neurophysiol. 50, 1197–1219 (1983).
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Thompson, L., Moskal, J. & Disterhoft, J. Hippocampus-dependent learning facilitated by a monoclonal antibody or D-cycloserine. Nature 359, 638–641 (1992). https://doi.org/10.1038/359638a0
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DOI: https://doi.org/10.1038/359638a0
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