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Effects of Transient Administration of the NMDA Receptor Antagonist MK-801 in Drosophila melanogaster Activity, Sleep, and Negative Geotaxis

Moulin, Thiago C. LU ; Stojanovic, Tijana ; Rajesh, Rasika P. ; Pareek, Tirusha ; Donzelli, Laura ; Williams, Michael J. and Schiöth, Helgi B. (2023) In Biomedicines 11(1).
Abstract

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,... (More)

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.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
circadian activity, climbing behavior, dizocilpine, fruit fly, glutamate receptor, invertebrates, psychiatric models, translational models
in
Biomedicines
volume
11
issue
1
article number
192
publisher
MDPI AG
external identifiers
  • scopus:85146886866
  • pmid:36672700
ISSN
2227-9059
DOI
10.3390/biomedicines11010192
language
English
LU publication?
yes
id
9ed2646c-8b90-42bc-9802-6e63bb2c7108
date added to LUP
2023-02-13 13:17:33
date last changed
2024-06-13 23:35:35
@article{9ed2646c-8b90-42bc-9802-6e63bb2c7108,
  abstract     = {{<p>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.</p>}},
  author       = {{Moulin, Thiago C. and Stojanovic, Tijana and Rajesh, Rasika P. and Pareek, Tirusha and Donzelli, Laura and Williams, Michael J. and Schiöth, Helgi B.}},
  issn         = {{2227-9059}},
  keywords     = {{circadian activity; climbing behavior; dizocilpine; fruit fly; glutamate receptor; invertebrates; psychiatric models; translational models}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{MDPI AG}},
  series       = {{Biomedicines}},
  title        = {{Effects of Transient Administration of the NMDA Receptor Antagonist MK-801 in Drosophila melanogaster Activity, Sleep, and Negative Geotaxis}},
  url          = {{http://dx.doi.org/10.3390/biomedicines11010192}},
  doi          = {{10.3390/biomedicines11010192}},
  volume       = {{11}},
  year         = {{2023}},
}