The Rewired Brain
Addictions permanently change the brain through a process called neuroplasticity. New research into the phenomenon helps explain opioids’ tight grip on so many.
While at the University of Minnesota for a postdoctoral fellowship in neuroscience, Dr. Matthew Hearing made a couple of timely observations that would help him specialize in a type of addiction that was about to explode into a staggering public health crisis.
Hearing saw opioid abuse skyrocketing and addiction researchers struggling to find theories to explain why. “I saw an obvious need to fill gaps in opioid research,” he says. “I recognized that we categorized addiction generally, across multiple classes of drugs, in just one basket.
“There was also almost nothing out there from a research standpoint in the area that I wanted to look at, which is neuroplasticity.” So Hearing saw his opening to conduct much-needed research.
Since returning to Marquette University where he studies as an undergraduate, Hearing, H Sci ’03, works alongside several Marquette neuroscientists at the forefront of opioid addiction research. Hearing’s special focus is on how neuroplasticity contributes to the development and persistence of addicted behavior.
“My concern is that opioid users don’t understand the permanent effect they’re having,” says Hearing. “People think if they are able to stop using, everything should reset. We know now that is absolutely not true, which is what ultimately leads to relapse.”
Simply put, neuroplasticity is the idea that the brain is always changing based on environmental factors and behaviors. From changes involving individual neurons to larger remappings of neural pathways, neuroplasticity allows the brain to compensate after injury, for example. But the brain can also be altered through actions like drug use, and not all drugs have the same effect. “Generally, there is some degree of overlap in neuroplasticity across all addictive drugs. The same circuits, those responsible for controlling decision-making and behavior, are the circuits that are affected,” Hearing says.
“However, we have seen in the lab with opioids, when given in the same regimen as a drug like cocaine, the plasticity does seem to be stronger and to involve more neuronal pathways. This could be one explanation as to why opioids seem to have more of a hold over people who are addicted compared to other drugs.”
Genetic and environmental predispositions also lead people to start using drugs in the first place, says Hearing, which then makes addictions more likely. “People used to write it off as a decision the person made to become addicted, but we know better than that now,” he says. “Addiction is ultimately a brain disease.”
With a predisposition toward addiction and the neuroplasticity that occurs as an addiction forms, a person’s brain undergoes often irreversible changes. “My concern is that opioid users don’t understand the permanent effect they’re having,” he says. “People think if they are able to stop using, everything should reset. We know now that is absolutely not true, which is what ultimately leads to relapse.”
Supported by a $1 million grant from the National Institute on Drug Abuse, Hearing is building from the basics: investigating how opioids affect plasticity in the nucleus accumbens (the brain’s reward system) and the prefrontal cortext (important for decision-making).
Hearing uses technology such as optogenetics, which allows him to manipulate animal neurons in real-time using light, in order to identify changes in the brain at the level of a single cell. His goal is to develop a new treatment for people with opioid addiction, which could include neuromodulation of affected areas, or basically using the brain’s own predisposition toward plasticity to help it heal. “Ultimately we want to discover what adaptations occur during use that lead to physical dependence and withdrawal,” Hearing says. Given the extreme physical and mental withdrawal symptoms affecting those who abruptly stop pain medications after long periods of use, “we need to find ways to counteract the changes in the brain that are causing those symptoms.”
Coming full circle
Nearly 15 years ago, Dr. David Baker, professor and associate chair of biomedical sciences at Marquette, spotted unique drive and scientific curiosity in Hearing, then an undergraduate running experiments in Baker’s lab on the neurobiology of cocaine addiction. With Baker’s guidance, Hearing went on to study at the Medical University of South Carolina — the “addiction science hub of the country,” Hearing says — where he received his doctorate in 2010.
Once a mentor and now a colleague, Baker calls understanding the biological basis of opioid addiction a paramount priority of modern biomedical science and says, “Matt and his research group are establishing a leading program that will meaningfully contribute to the understanding and treatment of addiction.”
— Jesse Lee