Alex Dopico, MD, PhD, and chair of the Pharmacology Department at UTHSC has spent more than 20 years researching the effects of addictive drugs, alcohol in particular, on the brain. The American Society of Addiction Medicine (ASAM) defines addiction as “a primary, chronic disease of the brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors.”
Dr. Dopico points out that for years addiction was seen as a moral issue where the addict’s choices were linked to a tainted moral or willpower. Today, current research indicates that addiction is associated with an actual “rewiring” of the brain. This happens as the brain goes through a series of alterations, beginning with recognition of reward and evolving into compulsive behavior.
The “reward system” of the brain registers all pleasures using a distinct signature: the release of dopamine in the ventral tegmental area and Nucleus Accumbens. Addiction affects the activity of these dopaminergic neurons and their interaction with other brain areas, including the hippocampus, which lays down memories of the hedonic experience, and the amygdala, which is involved in stress and drug craving. Moreover, current theories suggest that dopamine itself plays a role in learning and memory, necessary processes in going from liking something to becoming addicted to it.
“When we compare an addict’s brain to a healthy brain, there is a definitive difference in structure and function. In an addict, a given hedonic point is only reached in the presence of the addictive stimulus and, more often than not, it requires an increased exposure in amount and/or frequency to reach such point,” says Dopico. “As the condition progresses, fear and anticipation take over, and the addict requires the addictive stimulus to avoid the negative consequences of its absence. This stage is usually associated with a compulsive stimulus (e.g., drug-seeking).”
According to ASAM, genetics accounts for about half of the likelihood that an individual will develop an addiction. Other risk factors include environment, culture, trauma (particularly in childhood/early adolescence), early exposure to the substance, disruption of social support, problems in interpersonal relationships, etc. Like many chronic diseases, addiction often involves cycles of relapse and remission, where all the aspects mentioned above play a role. Therefore, Dr. Dopico suggests that addiction cannot be effectively treated or prevented without a comprehensive approach.
“A comprehensive approach is key to treating and preventing addictive behaviors. Since we know addiction is as much of a genetic issue as it is an environmental one, we have to look at treatment that way,” says Dopico.
Reflecting on President Obama’s new Precision Medicine Initiative, Dopico notes that we are entering into a new era of individualized care in which researchers, providers, and patients work together to develop individualized treatment plans. This approach to addiction could not align more perfectly with the idea of cross-collaborative team science that UTHSC fosters.
“At UTHSC, we have the opportunity of advancing across all aspects of addiction, as we boast powerful academic units that are excellent for fellowships and residency, and have a focus on collaborative research.”
Dr. Dopico is currently working on the development of a drug that targets membrane proteins that control physiological and behavioral changes associated with acute alcohol intoxication, in order to prevent or reverse those effects. His Method to Extend Research in Time (MERIT) Award grant, which is being funded by the National Institute on Alcohol Abuse and Alcoholism, is for $3.6 million over a 10-year span.
“The point of finding ‘alcohol antagonists’ would be to counteract the detrimental action of alcohol on brain circulation and blood flow during acute alcohol intoxication. However, treatment of chronic alcoholism would require much more than a ‘magic pill.’ A comprehensive approach is a must.”