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G3 (Bethesda). 2018 Aug 30;8(9):2941-2952. doi: 10.1534/g3.118.200374.

Acute Effects of Drugs on Caenorhabditis elegans Movement Reveal Complex Responses and Plasticity.

Author information

1
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, M5S 3E1 Canada.
2
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5S 3E1 Canada.
3
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, M5S 3E1 Canada andyfraser.utoronto@gmail.com.

Abstract

Many drugs act very rapidly - they can turn on or off their targets within minutes in a whole animal. What are the acute effects of drug treatment and how does an animal respond to these? We developed a simple assay to measure the acute effects of drugs on C. elegans movement and examined the effects of a range of compounds including neuroactive drugs, toxins, environmental stresses and novel compounds on worm movement over a time period of 3 hr. We found a wide variety of acute responses. Many compounds cause rapid paralysis which may be permanent or followed by one or more recovery phases. The recoveries are not the result of some generic stress response but are specific to the drug e.g., recovery from paralysis due to a neuroactive drug requires neurotransmitter pathways whereas recovery from a metabolic inhibitor requires metabolic changes. Finally, we also find that acute responses can vary greatly across development and that there is extensive natural variation in acute responses. In summary, acute responses are sensitive probes of the ability of biological networks to respond to drug treatment and these responses can reveal the action of unexplored pathways.

KEYWORDS:

Acute Response; C. elegans; Drug Assay; Movement

PMID:
30061375
PMCID:
PMC6118317
DOI:
10.1534/g3.118.200374
[Indexed for MEDLINE]
Free PMC Article

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