5 Questions With…
Veronica Alvarez, Ph.D. Senior Investigator, NIAAA Laboratory on Neurobiology of Compulsive Behaviors, NIH Intramural Research Program
As Chief of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Laboratory on Neurobiology of Compulsive Behaviors (LNCB), how would you describe your lab’s work to non-scientists?
Our laboratory focuses on understanding how alcohol and other substances change the brain and the connections among brain cells, or neurons. We think that some of the changes associated with alcohol use may explain why a subset of individuals develop a compulsion to consume alcohol and display a strong drive to seek it despite the negative consequences.
We explore an essential question: why are some people more prone than others to developing alcohol and other substance use disorders? Our hypothesis is that vulnerability lies within the patterns of brain wiring. Multiple factors play a critical role in determining how the brain is connected and wired: genes, developmental processes, environmental factors, previous experiences, stress, etc. We are very interested in understanding the vulnerability factors underlying the compulsive aspect of behavior, in part because discoveries in this field would be critical to improving treatment outcomes for people with alcohol and other substance use disorders.
Can you summarize some of your lab’s significant accomplishments?
Recently, our team discovered a causal link between two factors known to be important in alcohol use disorder (AUD). The first factor is low sensitivity to the sedative effects of alcohol; research suggests that individuals with a low sensitivity to alcohol have a higher likelihood of developing AUD. In animal models, this can be measured as an enhancement in alcohol-induced stimulation. The other factor is lower levels of dopamine receptors—D2 receptors—within the basal ganglia, a brain region that plays a critical role in the rewarding, or pleasurable, effects of alcohol and other substances and in the formation of habitual substance use. Individuals with AUD tend to have lower levels of dopamine D2 receptors.
Using a mouse model, the LNCB team found that lowering the levels of D2 receptors in the brain was sufficient to increase alcohol-induced stimulation and decrease alcohol sedation. We also showed that lower levels of D2 receptors cause an increase in the signaling and activity of another major dopamine receptor type—the D1 receptor. Increased activity of dopamine D1 receptors contributes to the stimulating effects of alcohol in these animal models and their increased preference for alcohol over natural rewards.
Collaboration has been a hallmark of your career—in fact, your research receives support from multiple NIH Institutes, and you currently direct the Center on Compulsive Behaviors within the NIH Intramural Research Program. Why is collaboration so central to your work?
In a sense, because I conduct basic research on the brain, it has been a natural development to collaborate across neuroscience disciplines. In fact, the National Institute of Neurological Disorders and Stroke (NINDS) has provided additional funds for my program since I started at NIAAA more than 10 years ago. In 2017, I was privileged—and felt it was very much a once-in-a-lifetime opportunity—to be invited to help start and direct the collaborative NIH Center on Compulsive Behaviors.
For me, scientific collaboration feels more like a need than a choice: I work so much better in teams! I get most of my best ideas from talking and discussing with others. I find it very stimulating and enriching to work as part of a team.
You have been honored as an outstanding mentor and were distinguished by NIH as an “agent of change” for greater diversity within the scientific community. What is the importance of these issues for you?
Working alongside the fellows and trainees is the most rewarding part of my work. Watching them learn and overcome challenges is inspiring. And I learn so much from them. I consider mentoring and training the next generation of scientists to be both an incredible privilege and a responsibility. I owe so much to my own mentors that I feel this is a way to give back.
Also, I am convinced that in order to solve most of the problems we face, we must bring together people with diverse viewpoints, disciplines, expertise, and cultural and socioeconomic backgrounds. In my experience, diverse teams of individuals are really effective in science.
You moved to the United States from Argentina after earning your Ph.D. at the University of Buenos Aires. In what ways has the experience of that transition shaped your outlook and career?
As I mentioned before, I truly believe that diversity has a unique role to play in science and our society. My background shaped my view of the world, and my rich, diverse training has given me unique tools. In Argentina, people have fewer resources, so we need, by necessity, to be creative and make things work. I learned two important lessons from a very young age: you have to make it work with what you have, and you need to go get whatever you are missing; you cannot just wait for it. Also, I had very committed teachers and mentors and an incredibly talented group of peers with whom I am still in touch.