Alcohol changes how your brain genes work. Changing them back may fight addiction. Science alert

Alcohol changes how your brain genes work.  Changing them back may fight addiction.  Science alert

Many people are wired to seek out and respond to rewards. Your brain interprets food as a reward when you’re hungry, and water as a reward when you’re thirsty.

But addictive substances like alcohol and drugs can overwhelm your brain’s natural reward pathways, leading to unbearable cravings and reduced impulse control.

It is a common misconception that addiction is the result of weak willpower. But the explosion of knowledge and technology in the field of molecular genetics has radically changed our basic understanding of addiction over the past decade. The general consensus among scientists and health care professionals is that there is a strong neurological, biological, and genetic basis for addiction.

As a behavioral neurogeneticist leading a team investigating the molecular mechanisms of addiction, I combine neuroscience and genetics to understand how alcohol and drugs affect the brain.

In the past decade, I have seen changes in our understanding of the molecular mechanisms of addiction, largely due to a better understanding of how genes are dynamically regulated in the brain. New ways of thinking about how addiction forms have the potential to change the way we approach treatment.

Alcohol and drugs affect the activity of genes in the brain

Each cell in your brain has your genetic code stored in long strands of DNA. In order for all this DNA to fit into the cell, it must be tightly packed. This is achieved by wrapping DNA around “bundles” of protein called histones. The regions where DNA is broken down contain active genes that encode proteins that serve important functions within the cell.

When gene activity changes, the proteins your cells produce also change. These changes can range from a single neural connection in your brain to how you behave.

This genetic choreography suggests that while your genes influence how your brain develops, the genes that are turned on or off when you learn new things are dynamic and adapt to suit your daily needs.

Recent data from animal models suggest that alcohol and drug abuse directly affects changes in gene expression in areas of the brain that help stimulate memory and reward responses.

Within each neuron in the brain, the extent to which DNA is wrapped around or bound to histones and other proteins determines which genes are expressed and which proteins are produced. (Carla Coon and Vinald Francis/CC BY-ND)

There are many ways in which addictive substances can change gene expression. They can change which proteins bind to DNA to turn genes on and off and which parts of DNA are uncoiled. They can change the process of reading DNA and translating it into proteins, as well as changing the proteins that determine how cells use energy to function.

For example, alcohol can cause an alternative form of a gene to be expressed in memory circuits in flies and humans, leading to changes in dopamine receptors and transcription factors involved in reward signaling and neural function. Likewise, cocaine can cause an alternative form of the gene to appear in mice’s reward centers, prompting them to seek out more cocaine.

It is not known exactly how these drugs cause changes in gene regulation. However, a direct link between alcohol consumption and changes in gene expression in mice provides a clue.

An alcohol byproduct broken down in the liver called acetate can cross the blood-brain barrier and unwind DNA from histones in mouse memory circuits.

Alcohol, nicotine, cocaine, and opioids also activate important signaling pathways that are central regulators of metabolism. This suggests that they can also affect many aspects of neuronal function and thus influence which genes are expressed.

Changing the activity of genes in the brain with lifestyle

How addictive substances alter cell function is complex. The copy of a gene you’re born with can be modified in several ways before it becomes a functional protein, including exposure to alcohol and drugs.

Rather than discouraging researchers, this complexity is empowering because it provides evidence that changes in gene expression in your brain are not permanent. It can also be changed by medications and lifestyle choices.

Many medications commonly prescribed to treat mental health disorders also affect gene expression. Antidepressants and mood stabilizers can change how DNA is modified and which genes are expressed. For example, a drug commonly prescribed to treat depression called escitalopram affects how tight a DNA wound is and can change the expression of genes important for brain plasticity.

In addition, mRNA-based therapies can specifically alter which genes are expressed to treat diseases such as cancer. In the future, we may discover similar treatments for alcohol and drug use disorder.

These treatments will likely target important signaling pathways associated with addiction, changing how brain circuits work and how alcohol and drugs affect them.

Lifestyle choices can also affect gene expression in your brain, although researchers don’t yet know if they can alter changes caused by addictive substances.

Like alcohol and drugs, dietary changes can affect gene expression in several ways. In flies, a high-sugar diet can reprogram the ability to taste sweetness by tapping into the gene expression network involved in development.

Intense meditation, even after just a day, can also affect gene regulation in your brain through similar mechanisms. Attending a month-long meditation retreat reduces the expression of genes that affect inflammation, and experienced meditators can reduce inflammatory genes after just one day of intense meditation.

Work in animal models has also shown that exercise alters gene expression by altering both histones and molecular marks directly bound to DNA.

This increases the activity of genes important for nerve cell activity and plasticity, supporting the idea that exercise improves learning and memory and can reduce the risk of dementia.

From Dry January onwards, many factors can have profound effects on your brain biology. Taking steps to reduce alcohol and drug consumption and follow healthy lifestyle practices can help stabilize and bring long-term benefits to your physical and mental health.Conversation

Carla Kaun, associate professor of neuroscience, Brown University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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