Research reportNMDA antagonist MK-801 impairs acquisition of place strategies, but not their use
Section snippets
Method
The research described herein was conducted under protocols that were reviewed and approved by the Radford University Institutional Animal Care and Use Committee.
Results
Data from rats receiving MK-801 in the first two replications of the study were discarded because of an error in the drug administration protocol, resulting in the loss of two rats from each of the drug–drug, vehicle–drug, and drug–vehicle conditions. Data from the rats run in the vehicle–vehicle condition in the first two replications were included in the final set of data, as inclusion or exclusion of the data from these rats did not alter the pattern of results obtained in the study.
A total
Discussion
The results of the present study show that treatment with MK-801 does not impair acquisition of a T-maze learning task, but does affect how the task is solved. Here, rats were trained on an appetitive T-maze position discrimination that could be solved using place or response strategies. The task was rapidly acquired by most rats, and there were no apparent differences between rats given MK-801 and those given vehicle injections in how long they took to reach criterion performance.
Acknowledgements
This research was done in partial fulfillment of a M.A. at Radford University. The authors would like to thank Pamela Jackson and Thomas Pierce of Radford University, and Donald K. Ingram and Peter R. Mouton of the Laboratory of Experimental Gerontology at the National Institute on Aging for their help in the editing and preparation of this manuscript.
References (45)
- et al.
The non-competitive NMDA antagonist MK-801 increases food intake in rats
Pharmacol Biochem Behav
(1997) - et al.
NMDA receptors—their role in long-term potentiation
Trends Neurosci
(1987) - et al.
MK-801 and AP5 impair acquisition, but not retention, of the Morris milk maze
Pharmacol Biochem Behav
(1990) First occurrence of hippocampal spatial firing in a new environment
Exp Neurol
(1978)- et al.
MK801 increases feeding and decreases drinking in non-deprived, freely feeding rats
Pharmacol Biochem Behav
(2001) Neurobiological views of memory
- et al.
Shifts in preferred learning strategy across the estrous cycle in female rats
Horm Behav
(2004) - et al.
MK-801 impedes the acquisition of a spatial memory task in rats
Pharmacol Biochem Behav
(1990) - et al.
Synaptic plasticity and learning II: do different kinds of plasticity underlie different kinds of learning?
Neuropsychologia
(1989) - et al.
Pretraining and the function of hippocampal long-term potentiation
Neuron
(2000)
Inactivation of hippocampus or caudate nucleus with lidocaine differentially affects expression of place and response learning
Neurobiol Learn Mem
Long-term potentiation as a candidate mnemonic device
Brain Res Brain Res Rev
Multiple parallel learning systems in the brain of the rat
Neurobiol Learn Mem
Distinct components of spatial learning revealed by prior training and NMDA receptor blockade
Nature
Distinct contributions of hippocampal NMDA and AMPA receptors to encoding and retrieval of one-trial place memory
J Neurosci
Long-lasting potentiation of synaptic transmission in the dentate area of the anesthetized rabbit following stimulation of the perforant path
J Physiol
Detailed behavioral analysis of water maze acquisition under APV or CNQX: contribution of sensorimotor disturbances to drug-induced acquisition deficits
Behav Neurosci
Spatial memory and N-methyl-d-aspartate receptor antagonists APV and MK-801: memory impairments depend on familiarity with the environment, drug dose, and training duration
Behav Neurosci
NMDA receptors and learning and memory processes
Curr Drug Targets
Switching memory systems during learning: changes in patterns of brain acetylcholine release in the hippocampus and striatum of rats
J Neurosci
Synaptic function of N-methyl-d-aspartate receptors in hippocampus
Cited by (9)
NMDA receptor blockade in the dorsolateral striatum impairs consolidation but not retrieval of habit memory
2023, Neurobiology of Learning and MemoryCitation Excerpt :Extensive evidence has indicated a critical role for glutamatergic mechanisms in the acquisition and consolidation of DLS-dependent habit memory. Systemic administration of NMDA receptor antagonist MK801 impairs acquisition and consolidation in a DLS-dependent cued water maze (Packard & Teather, 1997a; Farina & Commins, 2020; but see also, Mackes & Willner, 2006). Impairment in the cued water maze may also be observed following intra-DLS administration of NMDA receptor antagonist AP5 (Packard & Teather, 1997b).
MGluR3 knockout mice show a working memory defect and an enhanced response to MK-801 in the T- and Y-maze cognitive tests
2014, Behavioural Brain ResearchCitation Excerpt :Our hypothesis is that entering the right arm or right turn per se affects brain circuits differently in mGluR3-KO mice, disrupting subsequent working memory performance and enhancing sensitivity of the KO brain to the actions of MK-801. Considering this, it is interesting that MK-801 treatment has been shown to significantly increase the use of response strategy of rats in the rewarded T-maze arm discrimination learning paradigm [52], indicating that MK-801 influences processes related to turning behaviors. Based on mGluR3 expression patterns in the brain [8–10], putative alterations in the dopaminergic basal ganglia circuits might explain our observations.
Effects of the cognition impairer MK-801 on learning and memory in mice and rats
2011, Behavioural Brain ResearchCitation Excerpt :In our study, both the absence of learning during the acquisition phase and the lack of bias for the training quadrant during the probe trial are consistent with the interpretation that 0.1 mg kg−1 MK-801 disrupted the acquisition of the spatial Morris water escape task. Some published evidence suggests that spatial learning tasks, once acquired, may be insensitive to the cognition-modulating effects of NMDA antagonists [63]. The Morris task, once acquired, appears to be resistant to the effects of MK-801, i.e. MK-801 did not disrupt the use of acquired spatial information.
The double-H maze test, a novel, simple, water-escape memory task: Acquisition, recall of recent and remote memory, and effects of systemic muscarinic or NMDA receptor blockade during training
2011, Behavioural Brain ResearchCitation Excerpt :This is not surprising as the same dose of MK801 (0.03 mg/kg) was also found to be ineffective in a more complex task, namely a reference memory task in the water maze [27]. Regarding the preventive effects of increased training against the consequences of the high dose of MK801, it is worth mentioning that, in a T-maze, a dose of 0.06 mg/kg MK801 did not prevent acquisition of a reinforced alternation task [32] and did not disrupt the capability to perform a genuine place response in 7 out of 10 tested rats. The same has been observed in a water maze task [33].
Place vs. Response Learning: History, Controversy, and Neurobiology
2021, Frontiers in Behavioral NeuroscienceImpaired spatial memory and enhanced habit memory in a rat model of post-traumatic stress disorder
2017, Frontiers in Pharmacology