The genetic contribution to the development of alcohol use disorders (AUD’s) could be as high as 60%, yet the molecular pathways sparked into life by a drink have remained largely mysterious. But scientists have now established that the gene Rsu1 is pivotal in affecting naïve and acquired preferences to alcohol, and that holds true from humans to flies.
Behavioural, genetic and biochemical experiments all supported the findings, which have just been reported in the leading international journal Proceedings of the National Academy of Sciences of the United States of America.
The research was conducted by an international consortium of researchers led by Professor Adrian Rothenfluh of University of Texas Southwestern Medical Center at Dallas. The group included Dr Arun Bokde, Assistant Professor in Trinity College Dublin’s School of Medicine and the Trinity College Institute of Neuroscience (a member of the IMAGEN Consortium).
The group investigated the effect of alcohol on fly behaviour. When exposed to alcohol, the flies displayed behaviours similar to those of humans – low doses of alcohol cause disinhibition and increased locomotor activity, whereas higher doses led to loss of postural control and sedation. Flies also displayed addiction-like behaviour similar to mammals.
The researchers found that flies that lacked the protein Rsu1 (produced by normal copies of the Rsu1 gene) had a high naïve preference for alcohol, whereas those lacking it in specific parts of the brain initially showed normal naïve behaviours, but then failed to develop preferences in the same way that normal flies did.
To investigate potential applicability of the animal findings to humans, it is known that alcohol consumption leads to activation of the brain’s reward system and alcohol-related behaviour is associated with reward anticipation. The investigators found that variations in the same genes in adolescents were associated with increased brain activation when a higher reward was offered during a cognitive task.
Rsu1 was also associated with frequency of lifetime drinking in an adolescent sample and alcohol dependence in an adult sample. This supports the idea that Rsu1 is a vital product in nerve cells that send the messages to and from the brain that affect our preferences for alcohol, and our behaviour when drinking it.
Dr Bokde said: “The same gene in two different organisms is associated with alcohol behaviours. In this particular study the animal results led to the discovery of the influence of this gene in humans. This study underscores the need to understand the molecular mechanisms underpinning alcohol-related behaviours in humans. Knowing how these pathways work gives us some hope that we might design treatments to interact with the cellular pathways responsible for affecting our alcohol preferences.”
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