Alcohol and drugs rewire your brain by changing how your genes work – research is investigating how to counteract addiction’s effects

Many people are wired to seek and respond to rewards. Your brain interprets food as rewarding when you are hungry and water as rewarding when you are thirsty. But addictive substances like alcohol and drugs of abuse can overwhelm the natural reward pathways in your brain, resulting in intolerable cravings and reduced impulse control.

A popular misconception is that addiction is a result of low willpower. But an explosion of knowledge and technology in the field of molecular genetics has changed our basic understanding of addiction drastically over the past decade. The general consensus among scientists and health care professionals is that there is a strong neurobiological and genetic basis for addiction.

As a behavioral neurogeneticist leading a team investigating the molecular mechanisms of addiction, I combine neuroscience with genetics to understand how alcohol and drugs influence 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 addictions form have the potential to change how we approach treatment.

Alcohol and drugs affect brain gene activity

Each of your brain cells has your genetic code stored in long strands of DNA. For all that DNA to fit into a cell, it needs to be packed tightly. This is achieved by winding the DNA around “spools” of protein called histones. Areas where DNA is unwound contain active genes coding for proteins that serve important functions within the cell.

When gene activity changes, the proteins your cells produce also change. Such changes can range from a single neuronal connection in your brain to how you behave. This genetic choreography suggests that while your genes affect how your brain develops, which genes are turned on or off when you are learning new things is dynamic and adapts to suit your daily needs.

Recent data from animal models suggests that alcohol and drugs of abuse directly influence changes in gene expression in areas of the brain that help drive memory and reward responses.

Diagram magnifying the nucleus of a neuron, showing spirals of DNA wound around bundles of protein

Within each neuron in the brain, how tightly DNA is wound around or bound to histones and other proteins determines which genes are expressed and which proteins are produced.
Karla Kaun and Vinald Francis, CC BY-ND

There are many ways addictive substances can change gene expression. They can alter which proteins bind to DNA to turn genes on and off and which segments of DNA are unwound. They can change the process of how DNA is read and translated into proteins, as well as alter 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 the memory circuits in flies and people, resulting in changes in dopamine receptors and transcription factors involved in reward signaling and neuronal function….

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