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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).
Highlights
Repeated alcohol consumption in humans leads to an increase in tolerance to alcohol, a known alcohol‐associated behaviour that can be replicated in animal models.[1]
It is speculated that the gamma‐aminobutyric acid receptor A (GABAA) receptor is responsible for acute alcohol related changes in behaviour, but it is agreed amongst researchers that more work needs to be done before conclusive statements can be made.[8]
While these previous studies support the notion that gamma‐aminobutyric acid receptor B (GABAB) receptors play a role in addiction pathways, further investigations using GABAB receptor drugs have the potential to elucidate the specific addiction mechanisms that are affected by GABAB receptor activation or inhibition
Summary
Repeated alcohol consumption in humans leads to an increase in tolerance to alcohol, a known alcohol‐associated behaviour that can be replicated in animal models.[1]. GABAB receptor agonist, SKF 97541, and GABAB receptor antagonist, CGP 54626, (previously used in Drosophila by Dzitoyeva et al, Dacks et al, and Root et al.,10,21,22) were used to target the GABAB receptor to demonstrate that this receptor plays a role in alcohol sensitivity and tolerance.
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