Abstract
Several experiments were conducted to study the effects of the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, on learning and memory in the rat. Rats displayed impaired performance on several sensorimotor tests and appeared grossly intoxicated when treated IP with 0.2 mg/kg MK-801, but not when treated with lower doses (0.05 or 0.1 mg/kg). Postacquisition performance on two spatial learning tasks involving working memory protocols (reinforced alternation and radial arm maze) was impaired by MK-801 at intoxicating doses (≥0.2 mg/kg) but not at lower doses (0.05 or 0.1 mg/kg). Using a position habit reversal task, we found that rats could learn to reverse a position habit while under the influence of a nonintoxicating dose of MK-801 (0.1 mg/kg), but when tested on the following day performed as if they did not recall what they had learned. Thus, acute administration of a nonintoxicating dose of MK-801 disrupts the retention of new information learned under the influence of the drug but does not interfere with the performance of tasks that are well learned before the drug is administered. Whether the performance deficits on the spatial learning tasks observed only following intoxicating doses of MK-801 reflect an effect on memory is not clear.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Benvenga MJ, Spaulding TC (1988) Amnesic effect of the novel anticonvulsant MK-801. Pharmacol Biochem Behav 30:205–207
Collingridge GL, Kehl SJ, McLennan H (1983) Excitatory amino acids in synaptic transmission in the Shaffer collateral-commissural pathway of the rat hippocampus. J Physiol (Lond) 334:33–46
Danysz W, Wroblewski HT, Costa E (1988) Learning impairment in rats by N-methyl-d-aspartate receptor antagonists. Neuropharmacology 27:653–656
Finger S, Simons D, Posner R (1978) Anatomical, physiological, and behavioral effects of neonatal sensorimotor cortex ablation in the rat. Exp Neurol 60:347–373
Handelmann GL, Contreras PC, O'Donohue T (1987) Selective memory impairment by phencyclidine in rats. Eur J Pharmacol 140:69–73
Hepler DJ, Wenk GL, Cribbs BL, Olton DS, Coyle JT (1985) Memory impairments following basal forebrain lesions. Brain Res 346:8–14
Kesner RP, Hardy JD, Calder LC (1981) Phencyclidine and behavior: I. Sensory-motor function, activity level, taste aversion and water intake. Pharmacol Biochem Behav 15:7–13
Kesner RP, Hardy JD, Novak JM (1983) Phencyclidine and behavior: II. Active avoidance learning and radial arm maze performance. Pharmacol Biochem Behav 18:351–356
Lynch G, Baudry M (1984) The biochemistry of memory: a new and specific hypothesis. Science 224:1057–1063
McCann DJ, Winter JC (1986) Effects of phencyclidine, N-Allyl-N-normetazocine (SKF-10,047) and verapamil on performance in a radial maze. Pharmacol Biochem Behav 24:187–191
Mondadori C, Ortman R, Petschke F, Buerki H, D'Amato F, Meisburger JG, Fagg GE (1988) Task-dependent impairment or facilitation of learning by NMDA receptor blockade. In: Cavalheiro EA, Lehman J, Turski L (eds) Frontiers in excitatory amino acid research. Liss, New York, pp 419–426
Morris RGM (1988) Elements of a hypothesis concerning the participation of hippocampal NMDA receptors in learning. In: Lodge D (ed) Excitatory amino acids in health and disease. Wiley, New York, pp 297–320
Morris RGM, Anderson E, Lynch GS, Baudry M (1986) Selective impairement of learning and blockade of long-term potentiation by an N-methyl-d-aspartate receptor antagonist, AP5. Nature 319:774–776
Olney JW, Labruyere J, Price MT (1989) Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science 244:1360–1362
Robinson GS, Crooks GB, Shinkman PG, Gallagher M (1989) Behavioral effects of MK-801 mimic deficits associated with hippocampal damage. Psychobiology 17:156–164
Salt TE, Eaton SA (1988) Excitatory amino acid receptors and somatosensory transmission to the thalamus. In: Cavalheiro EA, Lehman J, Turski L (eds) Frontiers in excitatory amino acid research. Liss, New York, pp 451–454
Staubli U, Thibault O, DiLorenzo M, Lynch G (1989) Antagonism of NMDA receptors impairs acquisition but not retention of olfactory memory. Behav Neurosci 103:54–60
Stringer JL, Greenfield LJ, Hackett JT, Guyenet PG (1983) Blockade of long-term potentiation by phencyclidine and opiates in the hippocampus in vivo and in vitro. Brain Res 280:127–138
Tonkiss J, Morris RGM, Rawlins JNP (1988) 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
Wilkinson L (1987) SYSTAT: The system for statistics. Evanston, IL: SYSTAT, Inc.
Whishaw IQ, Auer RN (1989) Immediate and long-lasting effects of MK-801 on motor activity, spatial navigation in a swimming pool and EEG in the rat. Psychopharmacology 98:500–507
Whishaw IQ, O'Connor WT, Dunnett SB (1985) Disruption of central cholinergic systems in the rat by basal forebrain lesions or atropine: Effects on feeding, sensorimotor behavior, locomotor activity, and spatial navigation. Behav Brain Res 17:103–115
Wozniak DF, Stewart GR, Finger S, Olney JW (1989) Comparison of behavioral effects of nucleus basalis magnocellularis lesions and somatosensory cortex ablation in the rat. Neuroscience 32:685–700
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wozniak, D.F., Olney, J.W., Kettinger, L. et al. Behavioral effects of MK-801 in the rat. Psychopharmacology 101, 47–56 (1990). https://doi.org/10.1007/BF02253717
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02253717