2012 Keynote Speaker: Dr. Nora Volkow

Imaging Diseases of Poor Self-Control

Invited address by Nora Volkow, Ph.D., Director of the National Institute on Drug Abuse (NIDA)

Dr. Volkow, the director of the National Institute on Drug Abuse (and the great-granddaughter of Leon Trotsky) delivered the first invited address of the New Orleans meeting, with a fascinating talk on the way rewards are processed in the brain, and how these processes can go awry in addiction. Much of her work has focused on extensive explorations of dopamine (DA), a neurotransmitter that appears to play a critical role in reward processing.

Volkow began by describing the process by which rewards—like an unexpected edible treat—get encoded in the brain. The first time the treat is encountered, the food itself elicits an increase in dopamine, corresponding to a flood of subjective pleasure. Over time, however, dopamine levels begin to increase before the treat is ever consumed; for example, at the sight or smell of the food. That sensation of pleasure associated with the increase in dopamine also increases motivation to go eat the food, thereby ensuring survival for another day. In short, Volkow explained, these dopamine surges in anticipation of reward are critical for survival, and an enormous amount of mental resources—related to learning and memory—are committed to these processes.

All of this, however, was backdrop to explain a series of initially puzzling findings that, contrary to what many predicted for years, addicts—and Volkow's investigations have spanned addictions to drugs, alcohol, and even food—do not show an enhanced dopaminergic response to their substance of choice. In fact, in many of these individuals—current abusers as well as detoxed individuals—the consumption of drugs or closely-related chemical analogues was less effective at producing dopamine, and likewise produced reduced feelings of euphoria. Which led Volkow and her colleagues to ask the question: Why bother taking drugs at all if the drugs themselves are not rewarding?

For Volkow, the answer lay in learning and conditioned responses. And indeed, in a study that conditioned rats to pair a sound with cocaine, the cocaine-conditioned rats showed an increase in dopamine to the neutral conditioned sound that predicted the delivery of cocaine. In a series of studies involving human addicts, Volkow and her group have also shown that these cue-related increases in dopamine are associated with craving, which can be a powerful driver of addicted behavior. This same process appears to hold for both drugs and food—exposures to cues related to these substances produce an increase in dopamine, which in turn produces a powerful craving, which drives individuals to seek out the cued substance.

But cue-linked increases in dopamine are not the whole story—after all, most people find food rewarding, and yet not all are incapable of regulating their food intake. Thus, Volkow has also explored disruptions in the executive systms governing the more automatic dopaminergic responses. The prefrontal cortex (PFC), a region of the brain associated with executive functioning and control, contains dopamine receptors, and addicts appear to have fewer of these receptors. One possibility is that lower levels of receptors make an individual more vulnerable to addiction. Using rats, Volkow and her colleagues set out to demonstrate causality—that excessive exposure to drugs might lead to a decrease in DA receptors in the PFC. And indeed, after rats learned to self-administer alcohol, fewer DA receptors were observed in frontal regions. On the other hand, when injected with genes that increased the number of receptors in these areas, drinking behaviors were reduced.

Dr. Volkow's work has been instrumental in shifting the consideration of alcohol and substance abuse away from the idea that these addictions represent a moral failing and towards the notion that they may be behaviors driven by profound disruptions in reward circuits in the brain. More recently, Volkow and her colleagues have also observed decreases in DA receptors among morbidly obese individuals—and the more severe the obesity, the lower the number of receptors, suggesting a vicious cycle, whereby excessive consumption of food disrupts signals of satiety and results in reduced ability to regulate dopamine in the PFC, and this reduced regulatory ability itself then leads to increased consumption of food. Though this work is newer, and ongoing, it is possible that Volkow's work will eventually lead to a reconsideration of obesity as well. Where once it was considered a self-imposed condition driven by a lack of willpower, accumulating evidence suggests that food addiction closely resembles addictions of other kinds.