G protein alpha-q gene expression plays a role in alcohol tolerance in Drosophila melanogaster

Aleyakpo, Benjamin and Umukoro, Oghenetega and Kavlie, Ryan and Ranson, Daniel and Thompsett, Andrew and Corcoran, Olivia and Casalotti, Stefano O. (2019) G protein alpha-q gene expression plays a role in alcohol tolerance in Drosophila melanogaster. Brain and Neuroscience Advances, 3. ISSN 2398-2128 (In Press)

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Abstract

Ethanol is a psychoactive substance causing both short and long-term behavioural changes, in humans and animal models. We have used the fruit fly Drosophila melanogaster to investigate the effect of ethanol exposure on the expression of the Gɑq protein subunit. Repetitive exposure to ethanol causes a reduction in sensitivity (tolerance) to ethanol which we have measured as the time for 50% of a set of flies to become sedated after exposure to ethanol (ST50). We demonstrate that the same treatment that induces an increase in ST50 over consecutive days (tolerance) also causes a decrease of Gɑq protein subunit expression both at the mRNA and protein level. To identify whether there may be a causal relationship between these two outcomes, we have developed strains of flies in which Gαq mRNA expression is suppressed in a time and tissue specific manner. In these flies, the sensitivity to ethanol and the development of tolerance is altered. This work further supports the value of Drosophila as a model to dissect the molecular mechanisms of the behavioural response to alcohol and identifies G proteins as potentially important regulatory targets for alcohol use disorders.

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