Scientific Life

An interview with Nora Volkow [email protected]

Nora D. Volkow, MD became Director of the National Institute on Drug Abuse (NIDA) at the National Institutes of Health in May 2003. As a research psychiatrist and scientist, Dr Volkow pioneered the use of brain imaging to investigate the toxic effects and addictive properties of abusable drugs. Her studies have documented changes in the dopamine system affecting, among others, the functions of frontal brain regions involved with motivation, drive, and pleasure in addiction. She has also made important contributions to the neurobiology of obesity, attention-deficit/ hyperactivity disorder (ADHD), and aging. Dr Volkow was born in Mexico, attended the Modern American School, and earned her medical degree from the National University of Mexico in Mexico City, where she received the Robins award for best medical student of her generation. Her psychiatric residency was at New York University, where she earned the Laughlin Fellowship Award as one of the Ten Outstanding Psychiatric Residents in the USA. Dr Volkow spent most of her professional career at the Department of Energy’s Brookhaven National Laboratory (BNL) in Upton, NY, where she held several leadership positions including Director of Nuclear Medicine, Chairman of the Medical Department, and Associate Director for Life Sciences. In addition, Dr Volkow was a Professor in the Department of Psychiatry and Associate Dean of the Medical School at the State University of New York (SUNY)–Stony Brook. Dr Volkow has published more than 580 peer-reviewed articles and written more than 90 book chapters and non-peerreviewed manuscripts and has also edited three books on neuroimaging for mental and addictive disorders. In 2013, she was a Samuel J. Heyman Service to America Medal (Sammies) finalist, and she was inducted into the Children and Adults with ADHD (CHADD) Hall of Fame. She was elected to membership of the Institute of Medicine in the National Academy of Sciences and received the International Prize from the French Institute of Health and Medical Research for her pioneering work in brain imaging and addiction science. She has been named one of Time magazine’s ‘Top 100 People Who Shape Our World’ and was included as one of the 20 people to watch by Newsweek magazine in its ‘Who’s Next in 2007’ feature. She was also included in the Washingtonian magazine’s 2009 and 2011 lists of the ‘100 Most Powerful Women’ and named Innovator of the Year by U.S. News & World Report in 2000. 1 Did you always want to be a scientist? Yes. As far back as I can remember, I always wanted to be a scientist. I have always been extremely curious and 0165-6147/ Published by Elsevier Ltd.

have wanted to understand the reasons for things. When I was young, what intrigued me the most was to understand what made life possible – in a plant, an ant, or a person. As I grew older, I increasingly became interested in the causes of behavior, at both an individual and a collective level. I was fascinated by the diversity of individual behavioral responses to the same circumstances and intrigued at how humans adapted to their social contexts. This is what led me to recognize, when I was in high school, that I wanted to study medicine, and when I was in medical school, that I wanted to pursue specialized training in brain-related diseases. 2 How did you become interested in studying the neurological basis of substance abuse? As a medical student, when I first started doing preclinical research, I recognized the power of pharmacology, particularly drugs of abuse, for modifying the behavior of laboratory animals. I was mentored by Dr Julian Villareal, who studied the role of opioids in the management of pain and was interested in developing new analgesics without addictive properties. This was when I first saw monkeys press a lever thousands of times to receive intravenous cocaine and observed the complete disruption of their behavior with chronic drug exposure. Seeing this focused me on wanting to understand the mechanism by which a drug could overtake an animal’s motivation in such a profound way as to disturb its interest in food, other monkeys, or sleep. At the same time, at the clinic I was being exposed to patients with cirrhosis, trauma, or seizures due to alcoholism, patients with amphetamineinduced psychosis, and patients with neuropathies from inhalant abuse, and I was disturbed by the dismissal of and lack of attention to the root cause of these patients’ disorders (drug taking). In my fourth year of medical school, I was fortunate to have had Dr Dionisio Nieto as mentor during my rotation in the Neurology Institute; he exposed me for the first time to clinical research and led me to realize that research could lead to interventions that could improve the neurological and psychiatric outcomes in patients suffering from substance abuse disorders. 3 Do you have a favorite paper – your own or someone else’s? I have many favorite papers, but among them I think the papers from Kosterlitz’s and Akil’s groups that described for the first time the endogenous opioid system rise to the top. At the time, the notion that we synthesized our own endogenous opioids was a major revelation. It helped us understand why chronic exposure to opiates could result in physical dependence and addiction and Trends in Pharmacological Sciences, April 2015, Vol. 36, No. 4


Scientific Life eventually led to the development of opioid substitution therapies for the treatment of heroin addiction. 4 Has anything particularly surprised you during your investigation into mechanisms of substance abuse? The data always surprise me, since not infrequently I find that results do not support working hypotheses. Most notable among my own investigations: (i) finding that the prefrontal cortex was consistently disrupted in addicted patients, at a time when addiction was thought to be a disorder that predominantly disrupted limbic brain regions and one that did not involve cognitive processes; (ii) finding that, when consuming a dug, addicted individuals showed a very blunted increase in dopamine, which ran counter to the notion that addicted individuals have enhanced sensitivity to the rewarding effects of drugs, mediated through dopamine increases; and (iii) finding that addicted individuals had low levels of dopamine D2 receptors in their striatum, at a time when it was thought that blockade of dopamine D2 receptors would antagonize the rewarding effects of drugs. 5 We hear a lot about a ‘war on drugs’. Do you have any thoughts about this analogy? I would like to reword the phrase ‘war on drugs’ to ‘war on substance use disorders’ – just as we have coined the phrase ‘war on cancer’. What we are after is preventing and treating substance use disorders, which is the way that we will, in turn, conquer the devastating individual and social effects that arise from them. 6 What do you think it’s important for the general population to know about the human brain and substance abuse? The brain has many fascinating aspects that I would like the general public to be aware of, but as it relates to substance use disorders there are two that I would highlight. First, that the brain is neuroplastic: it physically changes as a function of experience and environmental exposures (including exposure to drugs). This allows the


Trends in Pharmacological Sciences April 2015, Vol. 36, No. 4

brain to learn and optimize responses to future challenges and to recover after injury, although it is a capacity that decreases with age. Neuroplasticity also underlies the long-lasting changes in the brain that result from chronic exposure to substances of abuse, which explains why an adolescent can become addicted faster than an adult: the brain is more neuroplastic during the teen years than during adulthood. Second, that our brains are hardwired to respond to rewards, which in turn motivate our behaviors; this is why drugs literally can hijack the motivational drive of an individual, as they directly stimulate reward centers. This highlights the importance, as a prevention strategy, of providing children and adolescents with environments that contain positive reinforcers and that give them opportunities to develop skills, form social bonds, and pursue healthy goals. 7 What is the best piece of scientific advice you’ve ever been given? Create strong collaborations, for they will expand the way you think and approach a scientific problem. 8 Tell us something that is exciting to you in your work right now. We have discovered that during alcohol intoxication, the alcohol metabolite acetate is used as an additional energy source by the human brain, which ordinarily relies on glucose, and that the brain’s reliance on acetate for energy is increased in alcoholism. So we are pursuing the clinical relevance of this effect, both as it relates to the adverse consequences of alcohol withdrawal, since alcohol withdrawal will result in deprivation of a favored energy substrate to the brain, and as it relates to how this effect may contribute to relapse, for conditioning to acetate as an energy source to the brain from alcohol’s metabolism may contribute to its rewarding effects. The therapeutic implications are that perhaps a ketogenic diet instituted during alcohol discontinuation and sustained through detoxification might diminish symptoms of alcohol withdrawal and decrease relapse.

An interview with Nora Volkow.

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