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Medical News Today: ‘We can completely reverse alcohol dependence’

Scientists have discovered a way to entirely remove the urge to drink alcohol compulsively in an animal model. The researchers hope that, with enough funding, a solution to this age-old problem might be on the horizon.
[Man out cold thanks to whiskey]
Could alcoholism finally be on the way out?

Alcohol has been brewed and consumed by humans for almost 10,000 years.

In 2014, 87.6 percent of Americans over the age of 18 reported that they had consumed alcohol at least once in their life.

Although commonly available, it is an incredibly addictive substance. In the United States, an estimated 16.3 million adults over the age of 18 have an alcohol use disorder, and around 88,000 people die from alcohol-related causes annually.

For these reasons, thousands of researchers are dedicated to understanding the causes behind a compulsive need to drink alcohol and ways in which it might be curbed.

The amygdala’s alcoholism neurons

A study, published this week in The Journal of Neuroscience, built on previous work on a certain subset of neurons that seem to play a substantial role in alcoholism.

The neurons in question make up just 5 percent of the total neurons in the amygdala and are referred to as the central nucleus of the amygdala; this subset of neurons have been shown to become activated by frequent alcohol use. The more an individual drinks, the more the neuronal circuit is reinforced. This then drives further alcohol use and addiction.

Researchers from The Scripps Research Institute (TSRI) set out to see if this neuronal group could be influenced and perhaps controlled.

To this end, lead author Giordano de Guglielmo designed a rat model in which the alcohol-activated neurons express a specific protein. This gave the team a unique ability to observe how these neurons behaved. Without the protein label, alcohol-linked neurons are very difficult to identify.

Once the specific neurons were labeled in this way, the researchers injected a compound that could inactivate only the alcohol-linked neurons. The neurons were effectively silenced, and the results were remarkable.

‘I wasn’t sure if I believed it’

Much to the researchers’ surprise, the rats completely stopped compulsively drinking alcohol. The change was not momentary, either, it lasted for as long as the rats were monitored.

Because the response was much stronger than expected, the team went on to run the experiment a second and third time to check the findings; each time, the results were the same. Once the specific amygdala neurons were silenced, the need for alcohol evaporated. As study leader Olivier George says: “It’s like they forgot they were dependent.”

When speaking with Medical News Today, George explained his surprise:

“[…] with classic pharmacology we usually observe a 20-40 percent decrease in drinking because the individuals are highly dependent (we model heavy alcoholism). Instead, here, the drinking went all the way back down to normal drinking, and without noticeable side effects; very unusual.

And, usually, to have long lasting effects like that, you need daily treatment, not a single one; it shows that we might have found alcoholism’s Achilles’ heel.”

Interestingly, the rats were still motivated to seek out and drink sugar water, proving that it wasn’t simply the brain’s entire reward system that had been short-wired. The rats also appeared to be protected from the physical symptoms of alcohol withdrawal, such as shaking.

Another interesting aspect of the study was a difference that the team found between casual binge drinking and addictive drinking. Switching the neurons off did not have an impact on nondependent drinking, the brain just switched on a new set of neurons and continued. Only compulsive, addictive alcohol use was prevented.

The future of alcoholism looks bright

The next challenge for the researchers is to track how alcohol-activated neuronal circuits form over time; and, of course, to see if the work is translatable into humans.

MNT asked George about the team’s next steps; they are already moving forward at quite a rate:

“We are now able to reversibly control these neurons with a laser using optogenetics. We can turn on and off drinking that way. We are also trying to find molecular targets in these neurons that could be targeted for medication development.”

Olivier George, TSRI assistant professor

They are also spreading their net further afield. George told MNT that the team is already “testing nicotine and methamphetamine dependence” in rats. And George’s vision does not stop there; MNT asked what research he would carry out if access to funds and technology was unlimited, and he said:

“I would laser capture these neurons and measure protein levels to identify the proteins that could be targeted using small molecules to develop a new compound that would produce the same effect without needing invasive pharmacogenetic techniques (including brain surgery, gene therapy, and brain implants). All the techniques are available, it is just a question of money at that point.”

With efforts, innovations, and insights such as these, alcohol dependency could, one day, be permanently solved.

Read how physical activity reduces some of alcohol’s harmful effects.

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