The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice
Abstract
It was shown in the present study that the selective non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e] caused a pronounced and dose-dependent increase in locomotion in mice pretreated with a combination of reserpine and alpha-methyl-para-tyrosine. Haloperidol pretreatment did not antagonize the MK-801-induced stimulation of locomotion. The findings are discussed in relation to the concept of a corticostriatothalamocortical negative feedback loop serving to protect the cortex from an overload of information and hyperarousal. Such a feedback loop would encompass i.a. corticostriatal glutamatergic neurons and it would be modulated by mesencephalostriatal dopaminergic neurons.
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Genetically-modified mouse models of NMDA hypofunction, including the Grin1 hypomorphic mouse and the Srr knockout mouse, revealed schizophrenia-relevant phenotypes and neurochemical deficits.
“Genetically-modified mouse models of NMDA hypofunctionincluding the Grin1 hypomorphic mouse 25 and the Srr knockout mouse 26 -have also revealed schizophrenia-relevant phenotypes and neurochemical deficits.”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [25]
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- Authors
- Carlsson, M., & Carlsson, A.
- Affiliations
- University of Gothenburg (SE)
- Venue
- Journal of Neural Transmission
- Published
- 1989-10
- Volume
- 75
- Issue
- 3
- Pages
- 221-226
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- OpenAlex
- W1972579416
- Cited by
- 423
- References
- 14
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 2 · 2016: 9 · 2015: 4 · 2014: 5 · 2013: 5 · 2012: 3
- FWCI
- 16.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- MK-801, NMDA receptor antagonism, locomotor stimulation, monoamine depletion, reserpine, alpha-methyl-p-tyrosine, haloperidol, glutamatergic neurons, dopaminergic neurons, hyperarousal, mice
- MeSH terms
- Animals, Dibenzocycloheptenes, Dose-Response Relationship, Drug, Haloperidol, Male, Methyltyrosines, Motor Activity, Reserpine, Biogenic Monoamines, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate, Receptors, Neurotransmitter, alpha-Methyltyrosine, Mice
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