Excitatory amino acid antagonists and memory: Effect of drugs acting at N-methyl-d-aspartate receptors in learning and memory tasks

doi:10.1016/0028-3908(90)90034-O

Neuropharmacology

Volume 29, Issue 12, December 1990, Pages 1111-1116

https://doi.org/10.1016/0028-3908(90)90034-O Get rights and content

Abstract

The role of $N- methyl- d -aspartate$ (NMDA) receptors in memory processes was examined using a Y-shaped maze and a step-through passive avoidance task in mice. In the Y-maze, the total number of arm entries, which represents locomotor activity and alternation behaviour, thought to reflect working memory, were measured. Competitive NMDA antagonists, CGS 19755 (cis-4-phosphonomethyl-2-piperidine-carboxylate) and CPP (3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphate), impaired spontaneous alternation at doses which reduced locomotion of mice. $N- Methyl- d -aspartate$ prevented the impairment of alternation and decrease of locomotor activity produced by CGS 19755 and CPP. These results suggest that NMDA-dependent processes are involved in the mechanisms of working memory. In contrast, the non-competitive NMDA antagonist, MK 801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate) dramatically enhanced the total number of arm entries, while reducing alternation behaviour. $N- Methyl- d -aspartate$ had no effect on MK 801-induced enhancement of locomotor activity and impairment of alternation. In the passive avoidance task, mice were trained to avoid entry into the dark compartment. At doses which impaired working memory in the alternation task, CPP, CGS 19755 and MK-801 reduced acquisition, when administered before training. $N- Methyl- d -aspartate$ antagonized the effect of CPP, CGS 19755 and MK-801. Neither CPP nor MK-801 affected retention, when administered immediately after training or before testing retention. $N- Methyl- d -aspartate$ had no effect on retention with high-intensity shock, but facilitated retention with low-intensity shock.

These findings suggest that NMDA antagonists may impair learning (storage) but have little or no effect on recall (retrieval) from long-term memory. Working memory may also be affected by treatment with NMDA antagonists. $N- Methyl- d -aspartate$ may enhance the performance of animals in a passive avoidance task.

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Excitatory amino acid antagonists and memory: Effect of drugs acting at N-methyl-d-aspartate receptors in learning and memory tasks

Abstract

Pharmac. Biochem. Behav.

Pharmac. Biochem. Behav.

Neurosci. Lett.

Long-term potentiation and NMDA receptors in rat visual cortex

Nature, Lond.

2-Amino-7-phosphonoheptanoic acid (AP7) produces discriminative stimuli and anticonflict effects similar to diazepam

Life Sci.

Anticonvulsant activity of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), a substance with potent anticonvulsant, central sympathomimetic and apparent anxiolytic properties

Drug Dev. Res.

Anticonvulsant action of excitatory amino acid antagonists

Science, Wash.

The role of NMDA receptors in certain kinds of learning

Homogeneity of single trial response tendencies and spontaneous alternation in the T-maze

Psych. Rep.

CGS 19755, a selective and competitive NMDA-type excitatory amino acid receptor antagonist

J. Pharmac. exp. Ther.

CPP, a selective N-methyl-d-aspartate (NMDA)-type receptor antagonist: characterization in vitro and in vivo

J. Pharmac. exp. Ther.

Excitatory amino acid antagonists and memory: Effect of drugs acting at $N- methyl- d -aspartate$ receptors in learning and memory tasks

CPP, a selective $N- methyl- d -aspartate$ (NMDA)-type receptor antagonist: characterization in vitro and in vivo