Many people are programmed to seek and respond to rewards. Your brain interprets food as rewarding when you’re hungry and water as rewarding when you’re thirsty. However, addictive substances such as alcohol and drugs can disrupt the natural reward pathways in your brain, resulting in irresistible cravings and decreased impulse control.
A popular misconception is that addiction is a result of low willpower. But the explosion of knowledge and technology in the field of molecular genetics has greatly changed our fundamental understanding of addiction in the last decade. The general consensus among scientists and health professionals is that addiction has a strong neurobiological and genetic basis.
As a behavioral neurogeneticist who leads a team investigating the molecular mechanisms of addiction, I combine neuroscience with genetics to understand how alcohol and drugs affect the brain. The past decade has 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 our approach to treatment.
Alcohol and drugs affect brain gene activity
Each of your brain cells has your genetic code stored in long strands of DNA. In order for all this DNA to fit into a cell, it must be tightly packed. This is achieved by wrapping DNA around protein “spools” called histones. The areas where DNA is unwound contain active genes that code 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 neuron connection in your brain to how you behave. This genetic choreography suggests that as your genes influence the development of your brain, which genes turn on and off as you learn new things are dynamic and adapt to fit your daily needs.
Recent data from animal models shows that alcohol and drugs of abuse directly affect changes in gene expression in areas of the brain that help activate memory and reward responses.
There are many ways that addictive substances alter gene expression. They can change which proteins bind to DNA and which parts of the DNA unwind to turn genes on or off. Just as they can change the process of how DNA is read and translated into proteins, they can also change 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, resulting in changes in dopamine receptors and transcription factors involved in reward signaling and neuron function. Similarly, cocaine may cause an alternative form of the gene to be expressed in the reward centers of mice, leading them to seek out more cocaine.
It is not known exactly how these drugs cause changes in gene regulation. However, the direct link between alcohol consumption and changes in gene expression in mice provides a clue. Acetate, a byproduct of the breakdown of alcohol in the liver, can cross the blood-brain barrier and unwind DNA from histones in mouse memory circuits.
Alcohol, nicotine, cocaine, and opioids all activate important signaling pathways that are central regulators of metabolism. This suggests that they may also affect many aspects of neuronal function and, as a result, which genes are expressed.
Changing brain gene activity by lifestyle
How addictive substances alter cell function is complex. The version of an innate gene can be changed in many ways, including exposure to alcohol and drugs, before it becomes a functional protein. This complexity further empowers researchers rather than discourages them, because it provides evidence that changes in gene expression in your brain are not permanent. They can also be changed by medications and lifestyle choices.
Many of the medications commonly prescribed for 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 commonly prescribed drug for depression called escitalopram affects how tightly DNA is wound and may change the expression of genes important in brain plasticity.
Additionally, mRNA-based therapies can specifically alter which genes are expressed to treat diseases such as cancer. We may discover similar treatments for alcohol and substance use disorders in the future. These treatments could potentially target key signaling pathways linked to addiction, altering the functioning of brain circuits and how alcohol and drugs affect them.
Lifestyle choices can also affect gene expression in your brain; but researchers don’t yet know if they can reverse the changes caused by addictive substances.
Dietary changes, such as alcohol and drugs, can also affect gene expression in many ways. In flies, a high-sugar diet can reprogram the ability to taste sweetness by tapping a gene expression network involved in development.
Even after just one day, intense meditation can affect gene regulation in your brain through similar mechanisms. Participating in 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.
Studies in animal models have also shown that exercise alters gene expression by altering both histones and 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 may reduce the risk of dementia.
Starting 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 healthy lifestyle practices can help stabilize your physical and mental health and provide long-term benefits.
This article is republished from The Conversation, an independent, nonprofit news organization providing facts and analysis to help you understand our complex world.
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.