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Effects of Transient Administration of the NMDA Receptor Antagonist MK-801 in Drosophila melanogaster Activity, Sleep, and Negative Geotaxis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and neuroscience. Lund Univ, Fac Med, Dept Expt Med Sci, S-22184 Lund, Sweden..ORCID iD: 0000-0001-7811-5383
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and neuroscience.
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2023 (English)In: Biomedicines, E-ISSN 2227-9059, Vol. 11, no 1, article id 192Article in journal (Refereed) Published
Abstract [en]

MK-801, also called dizocilpine, is an N-methyl-D-aspartate (NMDA) receptor antagonist widely used in animal research to model schizophrenia-like phenotypes. Although its effects in rodents are well characterised, little is known about the outcomes of this drug in other organisms. In this study, we characterise the effects of MK-801 on the locomotion, sleep, and negative geotaxis of the fruit fly Drosophila melanogaster. We observed that acute (24 h) and chronic (7 days) administration of MK-801 enhanced negative geotaxis activity in the forced climbing assay for all tested concentrations (0.15 mM, 0.3 mM, and 0.6 mM). Moreover, acute administration, but not chronic, increased the flies' locomotion in a dose-dependent matter. Finally, average sleep duration was not affected by any concentration or administration protocol. Our results indicate that acute MK-801 could be used to model hyperactivity phenotypes in Drosophila melanogaster. Overall, this study provides further evidence that the NMDA receptor system is functionally conserved in flies, suggesting the usefulness of this model to investigate several phenotypes as a complement and replacement of the rodent models within drug discovery.

Place, publisher, year, edition, pages
MDPI, 2023. Vol. 11, no 1, article id 192
Keywords [en]
fruit fly, invertebrates, glutamate receptor, dizocilpine, circadian activity, climbing behavior, psychiatric models, translational models
National Category
Pharmacology and Toxicology Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-497724DOI: 10.3390/biomedicines11010192ISI: 000916911300001PubMedID: 36672700OAI: oai:DiVA.org:uu-497724DiVA, id: diva2:1741846
Funder
Swedish Research Council, 2019-01066EU, Horizon 2020, 857394Gunvor och Josef Anérs stiftelseAvailable from: 2023-03-07 Created: 2023-03-07 Last updated: 2023-03-07Bibliographically approved

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Moulin, ThiagoWilliams, Michael J.Schiöth, Helgi B.

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