MK-801 and AP5 impair acquisition, but not retention, of the Morris milk maze

doi:10.1016/0091-3057(90)90140-D

Pharmacology Biochemistry and Behavior

Volume 36, Issue 1, May 1990, Pages 145-149

https://doi.org/10.1016/0091-3057(90)90140-D Get rights and content

Abstract

The effects of the NMDA blockers, AP5 and MK-801, were assessed in two spatial tests. AP5 (10 μg in 2 μl ICV, N=6), or MK-801 (0.07 mg/kg IP, N=6), significantly increased open-field activity in male Long-Evans rats in two 3-min tests (Days 1 and 2) compared to control groups receiving equal volume saline injections (N=12). In the Morris milk maze, NMDA blockade significantly impaired acquisition performance on two bblocks of six trials, which followed each open-field test. Only control animals showed evidence of acquisition on a drug-free retention test assessing latency to reach the expected platform area and number of crossings in the area on Day 4. Retention was tested in control animals under NMDA blockade on Day 6. There was no effect of NMDA blockade on retention in the Morris milk maze. These results support the hypothesis that NMDA receptors are critical for the initiation of synaptic modification underlying place learning, but are not necessary in synaptic transmission during retrieval of place information.

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Furthermore, analysis of swim strategies showed that MK-801 mice did not use cognitively demanding spatial search strategies as efficiently as control animals. It should be noted that some other studies did report effects of MK-801 on spatial learning (Filliat and Blanchet, 1995; Tao et al., 2016; Heale and Harley, 1990; McLamb et al., 1990), but Åhlander and colleagues pointed out that these effects were hard to dissociate from non-mnemonic behavioural effects (e.g., increase in locomotor activity; Ahlander et al., 1999). Analysis of motor behaviour in the current MWM test revealed no difference in swim speed and covered distance.
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Pharmacology Biochemistry and Behavior

Abstract

References (13)

APV, an N-methyl-deuterium-aspartate receptor antagonist, blocks the hippocampal theta rhythm in behaving rats

Brain Res.

The interaction between MK-801 and receptors for N-methyl-D-aspartate: Functional consequences

Neuropharmacology

Excitatory amino acids in synaptic transmission in the Schaffer collateral commissural pathway of the rat hippocampus

J. Physiol.

Excitatory amino acid neurotransmission: NMDA receptors and Hebb-type synaptic plasticity

Annu. Rev. Neurosci.

Anticonvulsant doses of MK-801 fail to block long-term potentiation in vivo or impair spatial memory in the rat

Neurosci. Lett.

The organization of behaviour

Cited by (170)

Acute effects of ketamine and esketamine on cognition in healthy subjects: A meta-analysis

Progression and stop organization reveals conservation of movement organization during dark exploration across rats and mice

NMDA receptor dependence of reversal learning and the flexible use of cognitively demanding search strategies in mice

MK-801 and memantine act differently on short-term memory tested with different time-intervals in the Morris water maze test

Rhythmic theta and delta activity of cortical and hippocampal neuronal networks in genetically or pharmacologically induced N-methyl-d-aspartate receptor hypofunction under urethane anesthesia

Memory in aged mice is rescued by enhanced expression of the GluN2B subunit of the NMDA receptor