Even Low Doses of Alcohol Cause Changes in Brain Circuitry

Brain Connections Technology

The study found that even low doses of alcohol prepared the brain for addiction.

How many drinks is too much?

According to a recent rodent study, even tiny amounts of alcohol may cause epigenomic and transcriptomic changes in brain circuitry in a region that is essential for the development of addiction.

The pathways that are involved in setting the brain up for addiction, according to researchers at the University of Illinois at Chicago, are also linked to the highs that come with drinking, such as euphoria and anxiolysis, a state of relaxed but awake sedation.

Subhash Pandey

Subhash Pandey, director of the UIC Center for Research in Alcohol Epigenetics. Credit: Joshua Clark/University of Illinois Chicago

“This suggests that when the brain experiences the anti-anxiety effects of alcohol and the mood lift — the relaxation and the buzz — it is also being primed for alcohol use disorder,” said the study’s senior author Subhash Pandey, the Joseph A. Flaherty endowed professor of psychiatry and director of the Center for Alcohol Research in Epigenetics in the UIC College of Medicine.

Pandey states that while the research does not, for instance, imply that one drink results in addiction in individuals, it does provide some insights into why certain people are more susceptible to alcohol use disorder.

“We’re seeing that dependent behaviors may not always be from long-term, high-quantity habits but a result of rapid epigenetic changes in the brain, which we show in this study may start happening even at low doses,” said Pandey, who is also a senior research career scientist at the Jesse Brown Veterans Affairs Medical Center.

A paper published in the journal Molecular Psychiatry details Pandey’s experiments, which studied rats under control and alcohol exposure conditions.

In the experiments, rodents were exposed to low concentrations of alcohol, and researchers watched as they navigated a maze. After that, the researchers used RNA sequencing to examine brain tissue samples they had obtained after euthanasia and searched for patterns in gene expression.

When the samples were analyzed, the researchers discovered that a gene known as hypoxia-inducible factor 3 alpha subunit, or Hif3a for short, was connected to behaviors such as how long rats remained in parts of the maze with enclosed (high anxiety) or open arms (low anxiety).

Alcohol increased Hif3a expression, even after low doses of exposure, and reduced anxiety. And, while many effects of alcohol are different among males and females, there was no difference between the two in this study.

“We saw that low doses, what we consider ‘social drinking,’ changes the gene expression in the amygdala, a brain region that regulates anxiety. In other words, it creates an epigenetic pathway for addiction,” Pandey said.

Pandey and his colleagues also set up additional experiments in which they blocked the gene in the amygdala of rats with or without alcohol exposure to validate its role in mediating anxiety. When Hif3a was blocked, anxiety was increased in control rats, mimicking withdrawal from chronic alcohol exposure. On the other hand, this also prevented the anti-anxiety effects of alcohol.

The researchers showed why, too. Hif3a’s chromatin — bundles of DNA and RNA — are loosely bundled, meaning the genes are easily accessible for transcription changes.

One thing the study does not suggest, however, is what level of alcohol exposure was safe for rodents. Instead, Pandey said, it’s important to know that low doses created priming for addiction. For people, he thinks the takeaway is simple — don’t assume social drinking or even “pandemic drinking” is without risk.

“Alcohol use disorder is complex and challenging to overcome. The information we learned from this study helps us to understand better what is happening in the brain and, one day, may be leveraged to develop better treatments and pharmaceuticals,” Pandey said.

Reference: “Unraveling the epigenomic and transcriptomic interplay during alcohol-induced anxiolysis” by Harish R. Krishnan, Huaibo Zhang, Ying Chen, John Peyton Bohnsack, Annie W. Shieh, Handojo Kusumo, Jenny Drnevich, Chunyu Liu, Dennis R. Grayson, Mark Maienschein-Cline and Subhash C. Pandey, 12 September 2022, Molecular Psychiatry.
DOI: 10.1038/s41380-022-01732-2

The study was funded by the National Institute on Alcohol Abuse and Alcoholism and the U.S. Department of Veterans Affairs.

26 Comments on "Even Low Doses of Alcohol Cause Changes in Brain Circuitry"

  1. People are not rats. Rats are not humans. Do research studies for humans with humans that sign consent forms. Not rats.

    • “We saw that low doses, what we consider ‘social drinking,’ changes the gene expression in the amygdala, a brain region that regulates anxiety. In other words, it creates an epigenetic pathway for addiction,”

      That this is even possible is a significant finding. It’s like you didn’t understand (or even read?) the article.

  2. Man, these science articles just keep getting dumber and dumber. “This just in, people like to feel calm and mellow the stress of life, and pursue things that help in relieving pain.” Holy sh!t!, you mean they don’t want to feel like crap?!! Here I thought people wanted to feel like garbage… well thanks to this article, written and published by these genius scientists, now I know! Get out of here.

  3. They can’t have people sign consent forms to be euthanized.

    • Marie B, I’m not sure this particular study could have been done on humans (after euthanasia)… Nor accurate . Pretty sure the rats were put to sleep soon after the test for accurate data.

  4. “We saw that low doses, what we consider ‘social drinking,’ changes the gene expression in the amygdala, a brain region that regulates anxiety. In other words, it creates an epigenetic pathway for addiction,”

    That this is even possible is a significant finding. It’s like you didn’t understand (or even read?) the article.

  5. James Adam Carrington | October 16, 2022 at 11:27 pm | Reply

    Yeah, I call total bs on this article! I have enjoyed alcohol most of my life; there were times when I was younger that, looking back, I was a heavy drinker, on and off; never experienced ANY withdrawal or anything. This is like those old “studies” that claimed that weed was a gateway drug and that it pretty much always leads to other drugs and other serious addictions; except that, truth be told, IT DOESN’T and it NEVER DID.
    no resulting alcoholism, and no addictions to any other substances, either, I might add. The huge red flag for this article is at the very end; look at who actually paid for/sponsored this entire study: Yep, an anti-alcohol organization who has a vested interest in depicting and “proving” just how bad drinking is! This thing is SKEWED AT BEST, just like those clods who push Alcoholics Anonymous. They would have the entire WORLD believe that even if you have one drink at some social function to relax a bit, well, oh, you have a problem with it…I disagree. I know many people who were told, brainwashed, that they were alcoholics when they were NOT, and NEVER WERE! The not-so-funny thing about AA is that, prior to someone stopping drinking, their families complained that they were never home, always out at a bar. So then, they get tricked into believing that they’re out-of-control alcoholics so they stop drinking, but guess what? They’re STILL never at home, they’re always out at some AA meeting or banquet or whatever, AND…they’ve just traded alcohol for coffee and those smelly Goddamned cigarettes that they CHAINSMOKE. All that happened is that they swapped one drug addiction for another one. PATHETIC as well as HORRIFICALLY DISINGENUOUS. This article is asinine and ridiculous. Now make me a whiskey sour, and…here’s to you!

  6. Absolutely fascinating, thank you for this great research!! And also disclosing the funding. This honestly seems like scientific evidence for the paradigm of alcohol explained in “How to control your alcohol” by Alan carr.

  7. I think the article was written very well. I’m glad you are furthering this research. Many efforts have been made to research addiction but we are still lacking so much insight and understanding. I am a bit disturbed about people posting such negative comments. I believe they have not read the entire publication since you mentioned that the rats were euthanized before testing.

  8. The comments are hilarious.

  9. Denise M. Salome | October 17, 2022 at 5:32 am | Reply

    Transcription changes? Extremely interesting but I didn’t understand the transcription part. Can someone elaborate on layman’s terms.

  10. Denise M. Salome | October 17, 2022 at 3:07 pm | Reply

    Bill and Bob figured this out 100 years ago

  11. Alcohol reaches inflamed parts of brain structures,Burns,damages nearly born cells,when burned ones are used cannot perform tasks required. Stop drinking, stop producing burning gases, new cells will replace burnt out ones, this is called recovery.. if damage to extensive must replace with basic cells material from umbelical cord??

  12. Some of these comments sure sound like someone struck a nerve

  13. Fantastic article! . . . Anyone disagreeing probably has a drinking problem themselves (LOL). The acceptance of the alcohol consumed within the US is startling as those aware of risks & diseases continue to consume only to damage their mind, body & spirit. Amazing how an individual diagnosed with liver damage, continues to consume alcohol; the smoker with COPD continues to smoke; the obese continue to stuff their faces. If only these individuals who disagree with your article could break out if their addictive behavior to actually enjoy life through being active versus a couch potato; and to eat to nourish their bodies versus emotionally stuffing their faces. These individuals could be naturally high on life with the health and vitality of the young, while experiencing sheer bliss versus coping out and using anything outside of oneself to change emotions within. We have the power within. Those that don’t use it are weak and it’s very sad. 😢 Take a good look in the mirror if my comment gets under your skin. You probably have a problem! Get help! You Only Live Once!

  14. The findings in this article are unique and significant. But what I find somewhat flabbergasting actually is the number of comments that in as anti-scientific language and reasoning as is humanly possible the resistance to people doing actual science.
    It’s almost as if people who don’t understand the scientific method read the article and then thought that their feelings were a legitimate response or argument against the findings of the article or even worse than feelings in my opinion they thought that they’re personal experiences were somehow an argument against the finding of the article.
    I know college isn’t for everyone but clearly even high school has failed our nation in so many ways or maybe it’s not just America here you know this could be anywhere in the world so I might be jumping to a conclusion there but that’s also a good point this article isn’t making any sweeping generalizations or pronouncements it’s just describing a scientific study.
    Everything in my comment is using voice to text and because I feel like I’m speaking to people with sub 8th grade educations or possibly just a sub 8th grade understanding of what sciences I’m speaking extremely slowly in a overly simplified way of speaking so that even a small child could understand my words.

    Let me put it another way: Nobody cares how you feel or what your experiences were and how those things show how invalid the study is.

  15. The comments are encouraging that people are starting to wake up to the biased, over-simplified, one-dimensional “studies” designed to eventually set-up a new drug “treatment” to make money.

  16. No! This is not “scientific”, and it doesn’t mean that people smart enough to see that are dumb or uneducated. It means the opposite! Remember, there was tons of “evidence” for MANY drugs, the latest of which has been the dubious use of anti-depressants in millions of people, that now, have no proof of actually working in most. So, rather than use personal attacks, which are completely unscientific by the way, consider, just for a moment, that it IS most likely B.S. because it’s over-simplifying a highly complex system for the benefit of those funding the study. How about not accepting every study that comes along, as legit, because it sounds “interesting”. How about a study showing how rats get high off money from grant research that keeps them in business. See how silly that is?

  17. Yea I did this study last night. According to my data and research, alcohol makes everything awsome!!! Scientifically speaking.

  18. This is just one study. From personal experience, I know alcohol abuse can ruin lives and it can often lead to more addictive drugs. Just because some clowns don’t want to face these facts doesn’t change. These same people are too ignorant about the dangers of alcohol because Miserable people love company…For you fools, just look at the statistics..DUH

  19. Just look at the chart, alcohol is one of the top dangerous drugs for human beings.

  20. I’ve watched friends who had alcohol addiction. This research is spot on.

  21. Ephraim ministries | October 22, 2022 at 9:55 am | Reply

    awesome article thank you for the updated facts.

  22. Thank you for this article. My large, extended family were non drinkers. Not as a conscious decision but just not part of the family culture. However, my generation (pre baby boomers) had our share of problem drinkers. I contribute it to opportunity and expendable income. I decided to give up alcohol decades ago and don’t miss it, but even now, in my late seventies, after a stressful day my mind will jump to a glass of wine. I’m not adverse to having the occasional glass but I don’t want to imbibe using any excuse. Reading these research results, I think my brain has been programmed by previous drinking habits. My husband has never had a drink in his long life and so drinking wasn’t a part of our family life. Fifty years ago he was a very popular designated driver! Pardon my ramblings but it has been my life experience that, overall,its best to forego any alcohol. It seems your research indicates that, hence some of the blowback in the comments.

  23. Interesting research, I’m not sure if many people here understand the similarities we have with rats, it’s causing confusion with many I see. Great work guys

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