Decoded: How People Get ‘High’ on Alcohol 

Researchers have revealed a twist in how alcohol intoxication happens by an experiment on fruit flies. 

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Researchers believe that this understanding could give insight as to why people use alcohol for pain management.
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As New Year's Eve approaches, many people will experience the familiar buzz by consuming their favourite cocktail, and now researchers have revealed a twist in how this intoxication happens.

When the cocktail reaches our nerve cells, the alcohol employs intermediary molecules on the membrane surface of the neuron to produce the intoxicating effect, said researchers from the Scripps Research Institute (TSRI) in the US.

In the study published in the Journal of Molecular Biology, the researchers enabled fruit flies to become inebriated to track ethanol's path.

The fly is a useful model to study gene activity because its genome is smaller than other animals and is easily manipulated.

The alcohol in beverages acts much like an anesthetic, said Scott Hansen, an associate professor at TSRI.

It creates a hyper “buzzed” feeling first, and then sedation, Hansen said.

It turns out there is an important intermediate step that was not previously known, researchers said.

They looked towards a system they have seen at play in anaesthesia to track alcohol's effects, starting with an enzyme on nerve cell membranes called phospholipase D2, (PLD2).

The enzyme links ethanol molecules to lipid (fat) in the membrane of the nerve cell.

The researchers found the enzyme becomes a catalyst triggering multiple downstream activities within the cell.

It creates a fatty alcohol metabolite called phosphatidylethanol (PEtOH).

That metabolite builds up and causes nerves to fire more easily, resulting in more hyperactive flies.

With hyperactivity you see the flies run around more, and this is what we equate to being buzzed
Scott Hansen

When the scientists knocked out the gene for the enzyme that makes the PEtOH metabolite, thus eliminating the signal, the flies did not become more active.

This is the first time this pathway has been identified as a determinant of alcohol sensitivity, Hansen said.

It remains to be seen whether the metabolite is involved in the full sedation experienced by the flies after the initial buzz and how this pathway may play a role in the hangover that many people experience later on.

Hansen says that his current research is addressing these questions.

Knowing alcohol's molecular targets could enable development of an antidote to intoxication, or even hangover, Hansen said.

The fatty alcohol is known to linger in the brain for more than 16 hours making it a likely target. Also, understanding this pathway could give insight as to why people use alcohol for pain management.
Scott Hansen

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