by Our brains experience a range of changes as we age, right down to the way your DNA is translated. Now, a new study has found that in people with cocaine use disorder these changes can accumulate at an accelerated rate.
Cocaine is one of the most addictive substances known to humans. It interferes with the brain’s reward pathways, forcing your cells to continue to send out pleasant signals until the drug wears off.
US estimates suggest that one in five people who use cocaine develop an addiction.
But exactly how a drug that interferes with the junctions between brain cells evokes addictive behaviors that, in turn, manifest themselves in substance abuse, is a chain of events that researchers are still trying to understand.
One possibility lies in non-coding modifications made to the DNA contained in brain cells, which alter the way their genes are turned on and off. So the research looked at the patterns of these so-called epigenetic changes in a region of the brain called Brodmann Area 9.
Situated in the prefrontal cortex – the front part of the brain behind the forehead – Brodmann’s Area 9 (BA9) is considered important for self-awareness and inhibitory control; two things that get mixed up in substance use disorders.
Much of what we know about what cocaine does to brain cells comes from studies in mice. Few investigations have examined the long-lasting effects of cocaine on human brain tissue, although two studies to date have detected regions of DNA that show excessive methylation in the brains of people addicted to cocaine.
This new study of human brain tissue recovered post-mortem found the same thing again: in BA9, cocaine users had sections of DNA spruced up with methyl groups — chemical changes that have been found to accumulate with age and in age-related diseases.
To arrive at these results, the researchers compared levels of DNA methylation in brain tissue samples from 21 people who had a cocaine use disorder and 21 people who did not.
DNA methylation is considered one of the molecular hallmarks of aging. Normally, the presence of more methyl groups decreases the activity of nearby genes because the cell’s machinery can no longer access the genetic instructions contained therein.
By knowing how methyl groups attach to DNA over time, DNA methylation can be used as an “epigenetic clock” to see whether tissues are aging faster or slower compared to their expected chronological age.
In this study, the researchers used two different epigenetic clocks to try to explain any variation.
“We detected a stronger biological aging trend of the brain in subjects with cocaine use disorder compared to subjects without cocaine use disorder,” says Stephanie Witt, senior author of the study and molecular biologist at the Central Institute of Mental Health in Germany. .
“This could be caused by cocaine-related disease processes in the brain, such as inflammation or cell death.”
The researchers think these molecular alterations may contribute to the high-level functional and structural changes seen in the brains of people with cocaine use disorder and, in turn, behavioral aspects of addiction.
Among the sequences that showed the strongest changes in DNA methylation in this study were two genes that, according to previous research, regulate behavioral aspects of cocaine intake in rodents.
However, the researchers acknowledge that their study was small and more research is needed, perhaps to see what molecular changes the brain accumulates over time with continued drug use.
“Since the estimation of biological age is a very recent concept in addiction research and is influenced by many factors, more studies are needed to investigate this phenomenon, with larger samples than possible here,” says Witt.
Larger studies would also help to disentangle the effects of other conditions, such as mood disorders, which so often accompany substance use disorders. Many of the deceased donors in this study suffered from major depression, which may have altered their brain function in other ways.
The researchers also noted whether the donors were intoxicated when they died or were using medication to treat depression or other conditions, although the study was too small to adjust for that.
However, it builds on previous studies of other brain regions to expand our understanding of how drug addiction can interfere with the brain.
“Looking at multiple regions of the brain allows for a more complete understanding” of the role of DNA methylation in cocaine use disorder, the researchers conclude.
The research was published in Frontiers in Psychiatry.
