Volkow Tells Story of Dopamine, Addiction, and Human Tragedy

When Nora Volkow, M.D., director of the National Institute on Drug Abuse, was a 5-year-old girl growing up with her family in Mexico City, a man came to the door one night bearing a telegram as the family was eating dinner.

Volkow’s mother read the telegram and began to cry. “I wanted to console her, but she did not want us to see her cry,” Volkow recalled as she presented the William C. Menninger Memorial Convocation Lecture at APA’s 2015 annual meeting in Toronto. “She left the room and locked the door behind her. Next morning, my father would tell us that my mother’s father, my grandfather, had died.”

Many years later, after Volkow had begun an extraordinary career as a brain researcher and addiction expert, her mother—herself now gravely ill—revealed a heartbreaking secret: Volkow’s grandfather had been an alcoholic and had committed suicide.

Volkow’s story was a surprising and heartfelt introduction—the difficulty of the memory was still evident in Volkow’s delivery all these years later—and it served as a starkly human illustration of the disaster wreaked by addiction on brain circuits that regulate motivation and reward seeking.

At the heart of that story is dopamine, which has been known for years to be central to a range of phenomena, but especially to reward and pleasure seeking. “All drugs increase dopamine in brain reward regions,” she said. “That in turn motivates our actions, which explains why behaviors that are rewarding—eating and sex, for instance—have been used by nature in order to ensure that we survive as an individual and as a species.” But as Volkow said, “Addiction hijacks that system.”

An early theory to explain the hijacking was that addicts were much more sensitive to the rewarding effects of drugs. Researchers believed that drugs would produce much larger increases in dopamine than in the nonaddict, thus explaining their enhanced motivation for taking the drug. But research began to emerge that showed something startling—just the opposite was true: people who were addicted to drugs showed much lower increases in dopamine in response to the drug. “This was completely counterintuitive,” Volkow said.

Yet it turned out to be consistent with the way dopamine in the brain responds to reward. For instance, a crucial finding was the discovery in animal models that in response to any kind of reward, the brain releases dopamine, but ceases to do so with repeated exposure to the reward; instead, the brain responds with dopamine release to the conditioned stimuli that predicts the reward.

Conditioned stimuli are those that are associated by temporal sequence or spatial presence with the actual experience of the reward. “Increasing dopamine in reward regions is what motivates our behavior, and if what nature is aiming for is to ensure we do the behaviors that will allow us to survive, then it wants you to be motivated to engage in the behavior. So by being conditioned, you will engage that motivational system that is anticipating the reward to ensure you do the behavior and procure the reward.”

This, Volkow said, is why people who are addicted to drugs or alcohol use them again and again—because they have been conditioned to the place where they take drugs, to the dealer who sells the drugs to them, to the friends with whom they get high, and to the emotional states that precede using the drugs.

Moreover, dopamine pathways are not limited to reward and motivation but are fundamental in the prefrontal areas of the brain regulating self-control, working memory, decision making, and judgment.

It is this disruption of myriad circuits regulating the human capacity to plan, to make judgments based on changing circumstances, and seek out that which is good for us and avoid that which is bad that causes the addict to behave in such a puzzling fashion. And that, in turn, is what accounts for the shame that surrounds the condition.

Volkow said, “I realized that my mother’s shame was not just because my grandfather had been alcoholic, but because he had committed suicide out of hopelessness and helplessness at his inability to control the strong urge to drink, to relapse again and again and again until that one last moment of self-hatred when he killed himself.

“This is my story and I live with it,” she said. “I wanted to share it with you so that this does not happen to our patients. If we embrace the concept of addiction as a chronic disease where drugs have disrupted the most fundamental circuits that enable us to make a decision and follow it through, we will be able to decrease the stigma not just in the lay public, but among providers and insurers so that people with mental illness do not have to go through obstacles to obtain the evidence-based treatments, so that they don’t feel that shame.

“And perhaps we will be able to feel empathy for our patients suffering from a disease we call addiction.” ■