Summary
Rats were trained to lever press on a differential reinforcement of low rates (DRL-18 s) schedule. They were then allocated to four treatment groups. These were: hippocampal aspiration lesions [HIPP]; implantation of osmotic minipumps for intraventricular infusion of either (a) the NMDA receptor antagonist 30 mM D, L-2-amino-5-phosphonopentanoic acid [AP5] or (b) vehicle [VEH]; and an unoperated control group [UNOP]. In subsequent DRL testing, the HIPP group showed a profound and enduring loss of efficiency, resulting from an increased tendency to respond too early; the AP5 group showed a qualitatively similar, but less severe, impairment followed by full recovery once the minipumps had expired; the VEH and UNOP groups both maintained their pre-operative levels of efficiency. We conclude that AP5 infusion disrupts temporary memory storage in the hippocampus, and that the hippocampus is concerned with the retention of memories outside the purely spatial domain.
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References
Agnew RL, Meyer ME (1969) Response inhibition of rats with medial and lateral septal lesions. Psychon Sci 16: 231–233
Anger D (1956) The dependence of interresponse times upon the relative reinforcement of different interresponse times. J Exp Psychol 52: 145–161
Barnes CA (1979) Memory deficits associated with senescence: a neurophysiological and behavioural study in the rat. J Comp Physiol Psychol 93: 74–104
Bliss TVP, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetised rabbit following stimulation of the perforant path. J Physiol (Lond) 232: 331–356
Boitano JJ, Dokla CJP, Mulinski P, Misikonis S, Kaluzynski T (1980) Effects of hippocampectomy in an incremental-step DRL paradigm. Physiol Behav 25: 273–278
Brookes S, Rawlins JNP, Gray JA, Feldon J (1983) DRL performance in rats with medial or lateral septal lesions. Physiol Psychol 11: 178–184
Carlton PL, Markiewicz B (1971) Behavioral effects of atropine and scopolamine. In: Furchtgott E (ed) Pharmacological and biophysical agents and behavior. Academic Press, New York, pp 345–373
Collingridge GL, Kehl SJ, McLennan J (1983) Excitatory aminoacids in synaptic transmission in the Shaffer collateral-commissural pathway of the rat hippocampus. J Physiol (Lond) 334: 33–46
Collingridge GL, Kehl SJ, McLennan J (1984) The action of some analogues of the excitatory amino acids in the dentate gyrus of the rat. Can J Physiol Pharmacol 62: 424–429
Deadwyler SA (1985) A physiological basis for hippocampal involvement in coding temporally discontiguous events. Behav Brain Sci 8: 500–501
Deadwyler SA, West MO, Christian EP, Hampson RA, Foster TC (1985) Sensory evoked potentials in the dentate gyrus represent item specific short-term information storage in the hippocampus. Behav Neural Biol 44: 201–212
Douglas RM, Goddard GV (1975) Long term potentiation of the perforant path-granule cell synapse in the rat hippocampus. Brain Res 86: 205–215
Errington ML, Lynch MA, Bliss TVP (1987) Long-term potentialtion in the dentate gyrus — induction and increased glutamate release are blocked by D(-) ammophosphonovalerate. Neuroscience 20: 279–284
Foster AC, Fagg GE (1984) Acidic amino acid binding sites in mammalian neuronal membranes: their characteristics and relationship to synaptic receptors. Brain Res Rev 7: 103–164
Garrud P, Rawlins JNP, Mackintosh NJ, Goodall G, Cotton MM, Feldon J (1984) Successful overshadowing and blocking in hippocampectomized rats. Behav Brain Res 12: 39–53
Harris EW, Cotman CW (1983) Effects of amino acid antagonists on paired-pulse potentation at the lateral perforant path. Exp Brain Res 52: 455–460
Jordan TC, Clarke GA (1983) Early undernutrition impairs hippocampal long-term potentiation in adult rats. Behav Neurosci 97: 319–322
Lynch GS, Baudry M (1984) The biochemistry of memory: a new and specific hypothesis. Science 224: 1057–1063
Mayer ML, Westbrook GL (1987) The physiology of excitatory amino acids in the vertebrate central nervous system. Prog Neurobiol 28: 197–276
McNaughton BL (1983) Activity dependent modulation of hippocampal synaptic efficacy: some implications for memory processes. In: Seifert W (ed) Neurobiology of the hippocampus. Academic Press, New York, pp 233–252
McNaughton BL, Morris RGM (1987) Hippocampal synaptic enhancement and information storage within a distributed memory system. TINS 10: 408–415
McNaughton BL, Barnes CA, Rao G, Baldwin J, Rasmussen M (1986) Long-term enhancement of hippocampal synaptic transmission and the acquisition of spatial information. J Neurosci 6: 563–571
Meldrum B (1985) Possible therapeutic applications of antagonists of excitatory amino acid neurotransmitters. Clin Sci 68: 113–122
Millenson JR (1971) A general language for on-line control of psychological experimentation. Behav Sci 16: 248–256
Monaghan DT, Cotman CW (1985) Distribution of N-methyl-D-aspartate-sensitive L-[H3]-glutamate-binding sites in rat brain. J Neurosci 5: 2909–2919
Morris RGM, Garrud P, Rawlins JNP, O'Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297: 681–683
Morris RGM, Anderson E, Lynch GS, Baudry M (1986) Selective impairment of learning and blockade of long-term potentialtion by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319: 774–776
O'Keefe J, Nadel L (1978) The hippocampus as a cognitive map. Oxford University Press, Oxford
Olverman HJ, Jones AW, Watkins JC (1984) L-glutamate has higher affinity than other amino acids for [H3]-D-AP5 binding sites in rat brain membranes. Nature 307: 460–462
Racine RJ, Milgram NW, Hafner S (1983) Long-term potentiation phenomena in rat limbic forebrain. Brain Res 260: 217–231
Rawlins JNP (1985) Associations across time: the hippocampus as a temporary memory store. Behav Brain Sci 8: 479–528
Rawlins JNP (1987) Time to close the store? Behav Brain Sci 10: 156–159
Rawlins JNP, Bennett RC (1980) A headholder for visually guided surgery in rats. Physiol Behav 24: 415–416
Rawlins JNP, Feldon J, Gray JA (1980) The effects of hippocampectomy and of fimbria section upon the partial reinforcement extinction effect in rats. Exp Brain Res 38: 273–283
Rawlins JNP, Winocur G, Gray JA (1983) The hippocampus, collateral behavior and timing. Behav Neurosci 97: 857–872
Richelle M, Xhenseval B, Fontaine O, Thone L (1962) Action of chlordiazepoxide on two types of temporal conditioning in rats. Int J Neuropharm 1: 381–391
Scoville WB, Milner B (1957) Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 20: 11–21
Sinden JD, Rawlins JNP, Gray JA, Jarrard LE (1986) Selective cytotoxic lesions of the hippocampal formation and DRL performance in rats. Behav Neurosci 100: 320–329
Teyler TJ, Discenna P (1986) The hippocampal memory indexing theory. Behav Neurosci 100: 147–154
Turski L, Schwarz M, Turski WA, Klockgether T, Sontag K-H, Collins JF (1985) Muscle relaxant action of excitatory amino acid antagonists. Neurosci Lett 53: 321–326
Watkins JC, Evans RH (1981) Excitatory amino acid neurotransmitters. Ann Rev Pharmacol Toxicol 21: 165–204
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Tonkiss, J., Morris, R.G.M. & Rawlins, J.N.P. Intra-ventricular infusion of the NMDA antagonist AP5 impairs performance on a non-spatial operant DRL task in the rat. Exp Brain Res 73, 181–188 (1988). https://doi.org/10.1007/BF00279671
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DOI: https://doi.org/10.1007/BF00279671