Alcohol use disorder affects millions worldwide, partly due to alcohol’s complex impact on the nervous system. Both short-term and long-term use alter brain cell function and disrupt communication in brain circuits, driving behaviors like craving and relapse.

Recent studies reveal how alcohol influences genes, cell processes, and neural circuits.

How Genetics Influence Drinking
Genetic differences influence how people are affected by alcohol, playing roles in both vulnerability and protection against alcohol use disorder. Some key genes involved in alcohol metabolism, such as ADH1B and ALDH2, have variants that reduce the risk of developing the disorder.

Other genes, including BDNF and EFHD2, affect brain function related to alcohol use. Variations in these genes can increase drinking behaviors or offer resilience against harmful effects.

Studies also highlight genes like β-Klotho, which influence alcohol consumption through brain reward circuits. Other genes can alter drinking patterns by affecting brain activity and signaling pathways.

Alcohol and Gene Control
Proteins regulate gene activity by binding to specific DNA regions. In rodents, chronic alcohol use increases gene activity in brain cells like neurons, astrocytes, and microglia, hinting that these proteins may play a key role in alcohol-induced brain changes.

For example, a protein called NF-κB influences drinking behavior by activating specific genes in brain regions like the nucleus accumbens and amygdala.

Similarly, Lmo4 alters gene expression in the amygdala, driving alcohol consumption. Some transcription factors appear to limit drinking and help prevent relapse, highlighting their complex roles in alcohol use regulation.

Alcohol and Splicing
Splicing enables a single gene to produce various transcripts. That's crucial for biological diversity.

Alcohol exposure disrupts this process, as seen in individuals with alcohol use disorder. Similar effects are noted in fetal brain tissue exposed to alcohol. Rodent and primate studies confirm widespread splicing changes after alcohol exposure.

In fruit flies, alcohol alters splicing in dopamine receptors, impacting memory formation.

Alcohol and Brain Adaptations
Proteins undergo chemical changes after being made, such as phosphorylation, which is key to nerve cell communication. Alcohol can interfere with these processes, leading to long-term changes in brain function and behavior.

Key enzymes in these changes regulate important pathways affecting motivation, memory, and emotional responses.

Repeated alcohol exposure can alter brain regions associated with decision-making and reward, making it harder to control drinking. An example is the kinase GSK3β. It affects alcohol motivation and anxiety but acts differently across brain regions.

Some protein signaling pathways promote excessive drinking, while others act to limit alcohol use. These effects are highly specific to different brain regions, highlighting the complex interaction between alcohol and the brain’s molecular systems.

Alcohol Alters Brain Circuits and Behavior
Studies have shown that alcohol alters the activity of neural circuits and receptors involved in decision-making and behaviors.

Specifically, it impacts dopamine signaling in the striatum, a brain region linked to motivation. This disruption of dopamine release patterns is associated with alcohol consumption and seeking in animal models.

Chronic alcohol use also affects neuropeptides, which are the signal molecules of the brain. These include neuropeptide Y and corticotrophin-releasing factor. The brain areas that control these peptides, such as the central amygdala and bed nucleus of the stria terminalis, become more active after prolonged alcohol use, affecting withdrawal symptoms and alcohol-seeking behavior.

Research has also explored how different brain regions communicate with each other to regulate alcohol intake. In animal models, changes in brain circuit activity, like those in the prefrontal cortex and striatum, have been linked to both alcohol use and relapse.

Recent research has uncovered new mechanisms behind alcohol use disorder, particularly focusing on how certain neurotransmitters, like dopamine and serotonin. Studies show that alcohol affects brain regions differently in males and females, leading to sex-specific outcomes. 

Wrapping it all up.
Ongoing studies on alcohol's impact on brain activity have led to potential treatment strategies, such as new drugs targeting specific enzymes or receptors.

Additionally, animal research has highlighted how individual differences in brain circuit activity can explain varying responses to alcohol. For example, certain neuron populations in the brain may make some animals more prone to compulsive drinking behaviors. By manipulating specific neurons, researchers have been able to influence drinking behavior, showing that controlling neural circuits may help treat alcohol use disorder.

The complexity of alcohol use disorder, with its wide-reaching effects on brain chemistry and circuits, requires more research to identify the most effective therapeutic targets.

One thing is for sure - alcohol affects the brain in multiple ways and on multiple levels!

About the scientific paper:

First author: Gabor Egervari, USA
Published in: Trends in Neuroscience, December 2022
Link to paper: https://www.cell.com/trends/neurosciences/abstract/S0166-2236(21)00187-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0166223621001879%3Fshowall%3Dtrue