Many people are wired to seek and respond to rewards. Your brain considers food a reward when you’re hungry and water a reward when you’re thirsty. But addictive substances like alcohol and drugs of abuse can override the natural reward pathways in your brain, leading to unbearable cravings and reduced impulse control.
A common misconception is that addiction is the result of low will power. But the explosion of knowledge and technology in the field of molecular genetics has changed our basic understanding of addiction over the past decade. The general consensus among scientists and health care professionals is that addiction has a strong neurobiological and genetic basis.
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 last decade, I have seen changes in our understanding of the molecular mechanisms of addiction, mainly due to a better understanding of how genes are dynamically regulated in the brain. New ways of thinking about how addictions shape the way we treat have the potential.
Alcohol and drugs affect brain gene activity
Your genetic code is stored in long strands of DNA in each of your brain cells. To get all that DNA into a cell, it needs to be packed tightly. This is achieved by winding the DNA around protein “spools” called histones. Areas of unbroken DNA 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 the way you behave. This genetic choreography suggests that while your genes influence how your brain develops, which genes are turned on or off when you’re learning new things that are dynamic and adapt to your daily needs .
Recent data from animal models suggest that alcohol and drugs of abuse directly affect changes in gene expression in areas of the brain that help drive memory and reward responses.
There are many ways in which addictive substances can alter gene expression. They can change the proteins that bind DNA to turn the genes on and off and change which parts of the DNA are left intact. They can change the process of how DNA is read and DNA is translated into proteins, as well as changing the proteins that determine how cells use energy to function.
For example, alcohol can cause a different form of gene expression in the memory circuits in flies and humans, causing changes in dopamine receptors and transcription factors involved in reward signaling and neuronal function. Likewise, cocaine can cause another type of gene to be expressed in the reward centers of mice, making them seek 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 offers a clue. A byproduct of alcohol broken down in the liver called acetate can cross the blood-brain barrier and release 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 thereby influence the genes that are expressed.
Change in brain gene activity with lifestyle
How addictive substances alter 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 discouraging researchers, this complexity is powerful because it provides evidence that changes in gene expression in your brain are not permanent. They can also be changed with medications and lifestyle choices.
Many medications prescribed for mental health disorders also affect gene expression. Antidepressants and mood stabilizers can change the way DNA is modified and the genes that are expressed. For example, a commonly prescribed drug for depression called escitalopram affects how tightly wound DNA is and can change the expression of genes important for brain plasticity.
In addition, mRNA-based therapies can specifically alter the genes that are expressed to treat diseases such as cancer. In the future, we may find similar therapies for alcohol and substance use disorder. These treatments could target important signaling pathways involved in addiction, changing how brain circuits function and are affected by alcohol and drugs.