Many people are programmed to seek and respond to rewards. Your brain interprets food as a reward when you are hungry and water as a reward when you are thirsty. But addictive substances like alcohol and drugs can overwhelm the natural reward pathways in your brain, resulting in intolerable cravings and impaired impulse control.
A popular misconception is that addiction is the result of low willpower. But an explosion of knowledge and technology in molecular genetics has dramatically changed our fundamental understanding of addiction over the past decade. The general consensus among scientists and healthcare 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 affect the brain. Over 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 develop have the potential to change the way we approach treatment.
Alcohol and drugs affect gene activity in the brain
Your genetic code is stored in long strands of DNA in each of your brain cells. In order for all that DNA to fit into a cell, it must be tightly packed. This is achieved by wrapping the DNA around ‘coils’ of proteins called histones. Areas where DNA is unwrapped contain active genes that code for proteins that perform 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 influence the way your brain develops, the genes that turn on or off when you learn new things are dynamic and adapt to your daily needs.
Recent data from animal models suggest that alcohol and drug abuse directly influence changes in gene expression in areas of the brain that help stimulate memory and reward responses.
There are many ways that addictive substances can alter gene expression. They can change which proteins bind to DNA to turn genes on and off and which DNA segments are unwound. They can change the process of how DNA is read and translated into proteins, as well as change the proteins that control how cells use energy to function.
For example, alcohol can cause an alternative form of a gene to be expressed in the memory circuits of flies and humans, resulting in changes in dopamine receptors and transcription factors involved in reward signaling and neuronal function. Similarly, cocaine can cause an alternative form of a gene to be expressed in the reward centers of mice, causing them to seek more cocaine.
How exactly these drugs cause changes in gene regulation is unknown. However, a direct link between alcohol consumption and changes in gene expression in mice provides a clue. A byproduct of alcohol that is broken down in the liver, called acetate, can cross the blood-brain barrier and unwind DNA from histones in the memory circuits of mice.
Alcohol, nicotine, cocaine and opioids also all activate important signaling pathways that are central regulators of metabolism. This suggests that they can also influence many aspects of neuronal function and consequently influence which genes are expressed.
Changing brain gene activity with lifestyle
How addictive substances change cell function is complex. The version of a gene you are born with can be modified in many ways before it becomes a functional protein, including exposure to alcohol and drugs. Rather than discourage researchers, this complexity is actually empowering because it provides evidence that changes in gene expression in your brain are not permanent. They can also be modified by medications and lifestyle choices.
Many commonly prescribed medications for mental disorders also affect gene expression. Antidepressants and mood stabilizers can change how DNA is modified and which genes are expressed. For example, a commonly prescribed antidepressant drug called escitalopram affects how tightly DNA is coiled and can change the expression of genes important for brain plasticity.
Furthermore, mRNA-based therapies can specifically change which genes are expressed to treat diseases such as cancer. In the future, we may discover similar therapies for alcohol and substance abuse. These treatments could potentially target key signaling pathways linked to addiction, changing the way brain circuits function and the way alcohol and drugs affect them.
Lifestyle choices can also affect gene expression in your brain, although researchers don’t yet know whether they can alter the changes caused by addictive substances.
Like alcohol and drugs, dietary changes can affect gene expression in many ways. In flies, a high-sugar diet can reprogram the ability to taste sweetness by tapping into a gene expression network involved in development.
Intense meditation, even after just one day, can also influence gene regulation in your brain through similar mechanisms. Attending a month-long meditation retreat reduces the expression of genes that influence inflammation, and experienced meditators can reduce inflammatory genes after just one day of intensive mediation.
Research in animal models has also shown that exercise alters gene expression by altering both histones and the molecular tags directly attached to DNA. This increases the activity of genes important for the activity and plasticity of neurons, supporting the idea that exercise improves learning and memory and can reduce the risk of dementia.
From Dry January and beyond, many factors can have profound effects on your brain biology. Taking steps to reduce alcohol and drug consumption and adopting a healthy lifestyle can help stabilize and provide long-lasting benefits to your physical and mental health.
This article is republished from The Conversation, an independent nonprofit organization providing facts and analysis to help you understand our complex world.
It was written by: Karla Kaun, Brown University.
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Karla Kaun receives funding from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the National Institute of General Medical Sciences.
