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Pharmacological targeting of the GABAB receptor alters Drosophila's behavioural responses to alcohol

Ranson, Daniel C
Ayoub, Samir S.
Corcoran, Olivia
Casalotti, Stefano O
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Abstract
When exposed to ethanol, Drosophila melanogaster display a variety of addiction-like behaviours similar to those observed in mammals. Sensitivity to ethanol can be quantified by measuring the time at which 50% of the flies are sedated by ethanol exposure (ST50); an increase of ST50 following multiple ethanol exposures is widely interpreted as development of tolerance to ethanol. Sensitivity and tolerance to ethanol were measured after administration of the gamma-aminobutyric acid receptor B (GABAB) agonist (SKF 97541) and antagonist (CGP 54626), when compared with flies treated with ethanol alone. Dose-dependent increases and decreases in sensitivity to ethanol were observed for both the agonist and antagonist respectively. Tolerance was recorded in the presence of GABAB drugs, but the rate of tolerance development was increased by SKF 97451 and unaltered in presence of CGP 54626. This indicates that the GABAB receptor contributes to both the sensitivity to ethanol and mechanisms by which tolerance develops. The data also reinforce the usefulness of Drosophila as a model for identifying the molecular components of addictive behaviours and for testing drugs that could potentially be used for the treatment of alcohol use disorder (AUD).
Citation
Ranson, D.C., Ayoub, S.S., Corcoran, O., Casalotti, S.O. (2020) Pharmacological targeting of the GABAB receptor alters Drosophila's behavioural responses to alcohol. Addiction Biology. 2020;25 https://doi.org/10.1111/adb.12725
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PubMed ID
30761704 (pubmed)
PubMed Central ID
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Journal article
Language
en
Description
© 2020 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1111/adb.12725
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ISSN
1355-6215
EISSN
1369-1600
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Gov't Doc #
Sponsors
This work was carried out at the University of East London with the support of a PhD Studentship awarded to DCR from the Society for the Study of Addiction.
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Licence for published version: Creative Commons Attribution 4.0 International
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