The Role of Gamma-Aminobutyric Acid B Receptors in Alcohol Related Behaviours in Drosophila Models of Ethanol Tolerance and Preference

2017 dissertation for MRes. Alcohol is one of the most widely used and socially accepted psychoactive substances in the world, and its misuse was accountable for 3.3 million alcohol related deaths in the world in 2015. Whilst it is known that ethanol enhances the actions of the GABAB receptor, the role of the stimulation of this receptor in inducing acute and chronic effects, remains to be fully understood. The fruit fly, Drosophila melanogaster, offers the possibility to investigate behaviours such as preference and tolerance to alcohol, and to challenge them with pharmacological agents. In this study, the GABAB receptor agonist (SKF 97451) and antagonist (CGP 54626) were used to challenge the development of tolerance and the onset of preference to alcohol in wild type flies and in mutant lines with putative disruptions of GABAB receptor 1 or 2 subunit genes. Both compounds were able to alter the onset of tolerance measured as the time needed for half of a set of flies to be sedated by alcohol. Additionally, both drugs affected the preference developed by the flies towards alcohol containing food measure in a capillary feeder assay. The GABAB receptor mutant flies provided further evidence that the receptor is involved in the behavioural process studied. Overall the results indicate that the GABAB receptors are indeed part of a complex mechanism that result in alcohol induced behavioural changes. The data supports the usefulness of the Drosophila model and the need of further investigations into the GABAB receptor and to other potential pathways and mechanisms that could be contributing to the onset of such behaviours.