Scientists discover protein that turns places into binge-drinking ‘triggers’

Addiction specialists advise alcoholics to steer clear of their favorite bars and drinking buddies – and now scientists have found that booze changes the brain to turn these familiar things into ‘triggers.’

Researchers at the University of Pennsylvania (U Penn) discovered epigentic changes – alterations to the way DNA is expressed – caused by alcohol that, in turn, influence the brain’s learning system. 

In the case of booze, it teaches the brain to respond to familiar people, places and things that once would have paired well with a drink with the urge to consume alcohol. 

And the researchers think their discovery could lead to the development of a treatment that harnesses the gut brain connection to quiet the effects of environmental drinking cues to help treat alcohol addiction. 

Alcohol boosts levels of a protein that helps the brain encode memories of fami places – and suppressing that protein could help turn ‘off’ the urge for alcoholics to drink in familiar bars 

When someone goes to rehab for drinking, specialists may treat them with medication and therapy. 

But one of the key components of these in-patient facilities is simply their location. 

They offer a respite from old patterns, people and places that are associated with an addiction. 

About 90 percent of alcoholics experience a relapse, according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA). 

Relapses are often responses to environmental and social cues that tell the brain: ‘drink.’ 

Although addiction is now widely recognized as a physiological illness – not simply a lack of will power to be blamed on a person struggling with an addiction – much about how it actually works in the body remains unknown. 

But the latest study sheds some light on what is happening inside the body of an addict when they encounter a drinking cue. 

Acetate forms in the body when alcohol is broken down by the liver. 

In previous U Penn work, researchers found that acetate alters the protein packaging of bits of DNA that code for the production of an enzyme known as ACSS2. 

ACSS2 acts like the first domino in a series of on/off switches among genes in nerve cells that, in turn, activate genes that tell the memory it’s time to learn. 

In particular, acetate from alcohol metabolism sets this series of events into quick motion, priming us to form spatial memories. 

The link between alcohol and memory formation made the research team think they might be onto the pathway that explains relapse cues. 

So they conducted the new study to test whether controlling ACSS2 – the memory enzyme with a penchant for booze – in mice could affect the way the alcohol-exposed animals would respond to environmental triggers to binge. 

In one distinct compartment of their enclosure, the animals were given alcohol, forming a link between drinking and that place. In the other distinguishable compartment, the animals got no booze. 

After getting them used to spending time in each room, the mice were set free to roam from room to room of the enclosure. 

Unsurprisingly, they remembered the room that offered all the free drinks, and tended to spend more time in it. 

That is, until the researchers put a cap on the levels of the ACCS2 protein in the parts of their brains responsible for learning and memory formation. 

With less ACCS2, the mice didn’t care which room – the sober house or the bar – they spent time in. 

‘This indicates to us that that alcohol-related memory formation requires ACSS2,’ said Dr Gabor Egervari said, one of the study’s co-authors. 

‘Our molecular and behavioral data, when taken together, establish ACSS2 as a possible intervention target in alcohol use disorder – in which memory of alcohol-associated environmental cues is a primary driver of craving and relapse even after protracted periods of abstinence.’ 

Senior study author, Dr Shelley Berger, said: ‘It was a huge surprise to us that metabolized alcohol is directly used by the body to add chemicals called acetyl groups to the proteins that package DNA, called histones.’ 

‘To our knowledge, this data provides the first empirical evidence indicating that a portion of acetate derived from alcohol metabolism directly influences epigenetic regulation in the brain.’