Even low doses of alcohol cause changes in brain circuits

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

How many drinks a lot?

According to a recent study of rodents, even trace amounts of alcohol may cause epigenomic and transcriptional changes in brain circuits in a region essential to the development of addiction.

According to researchers at the University of Illinois at Chicago, the pathways involved in preparing the brain for addiction, are also linked to the benefits that come with drinking, such as euphoria and anxiety, a calm, relaxed but awakened state.

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 and mood-improving effects of alcohol – relaxation and tinnitus – it is also primed for alcohol use disorder,” said study senior author Subhash Pandey Joseph Flaherty. Professor of Psychiatry and Director of the Center for Alcohol Research in Epigenetics at UIC School of Medicine.

Pandey says that although the research, for example, does not imply that a beverage causes individuals to become addicted, it does provide some insights into why some people may develop an alcohol use disorder.

“We are of the view that dependent behaviors may not always be the result of long-term, high-quantitative habits, but rather the result of rapid epigenetic changes in the brain, which we show in this study may begin to occur even at low doses,” said Pandey, who is also the lead researcher. at Jesse Brown Veterans Affairs Medical Center.

A paper published in the magazine Molecular Psychiatry Details of Pandey’s experiments, which studied mice under control and alcohol exposure conditions.

In experiments, rodents were exposed to low concentrations of alcohol, and researchers watched as they navigate a maze. Then the researchers used

RNA is a polymeric molecule similar to DNA and is essential in various biological roles in coding, decoding, regulating, and expressing genes. Both are nucleic acids, but unlike DNA, RNA is single-stranded. The RNA strand contains a backbone made up of alternating groups of sugar (ribose) and phosphate. Attached to each sugar is one of four bases – adenine (A), uracil (U), cytosine (C), or guanine (C). There are different types of RNA in the cell: messenger RNA (mRNA), ribosomal RNA (rRNA), and carrier RNA (tRNA).

“data-gt-translate-attributes=”[{” attribute=””>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

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.

#doses #alcohol #brain #circuits

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