United Press International
Thursday, April 10, 2003
Using state-of-the-art technology, researchers for the first time have measured, to the split-second, the chemical trigger that makes it difficult for addicts to just say, "No," to drugs, food, sex or other over-indulgences.
The advance, accomplished by a team of psychologists, neuroscientists and chemists from the University of North Carolina at Chapel Hill, could pave the way toward novel treatments for habits that exact a heavy price, in health as well as dollars, investigators told United Press International.
"Our findings are extremely significant because we have identified a dynamic signal in the brain that is highly influential on drug-taking," said Paul Phillips, research assistant professor of psychology. "Identifying signaling mechanisms that drive drug-taking provides potential targets for therapeutic intervention."
Due to a lack of standardized classification methods, global addiction statistics are hard to come by, but officials attest to their epidemic proportions.
For example, the United Nations International Drug Control Program estimates marijuana alone has 141 million users worldwide. In the United States, a 2001 survey showed some 15.9 million Americans 12 or older partook of illicit drugs. The Substance Abuse and Mental Health Service Administration blamed the practice for 601,776 hospital emergency department visits that year.
The U.S. Department of Health and Human Services has implicated drug and alcohol overuse in the death of more than 120,000 Americans each year and in an annual bill totaling more than $294 billion in health care, lost productivity and other related costs.
In their rat study, detailed in the April 10 issue of the British journal Nature, the scientists offer a much-anticipated solution to a "chicken-and-egg" puzzle of neurochemical cause and effect in addiction. They identify the key player as dopamine, the chemical that transports directives from the brain to other parts of the body.
Dopamine is known to increase in levels during addictive behaviors, such as eating, taking drugs or having sex. Experiments revealed the brain releases the substance before as well as during pleasurable acts. Because the nervous systems of both rats and humans are similar when stimulated, scientists said they expect the rat results to apply to human research.
In a critical difference from past surveys -- which gave a minute-by-minute account of brain processes underlying addiction -- the new research presents information about what happens over fractions of a second.
"The problem with previous methods is that they did not provide enough resolution to determine if dopamine release occurs before drug seeking is triggered," said David Self, associate professor of psychiatry and Lydia Bryant Test professor at the University of Texas Southwestern Medical Center in Dallas, who analyzed the findings.
"The implications of this study are that split-second dopamine changes are sufficient to influence drug-taking behavior," Phillips told UPI.
The high-tech investigation was made possible by a cutting-edge electrochemical technique called fast-scan cyclic voltammetry, pioneered by Mark Wightman, Kenan professor of chemistry and neuroscience at UT Southwestern.
"Without the advances in his lab and his expertise, this project would have been technically unfeasible," Phillips emphasized.
Phillips, Wightman, Regina Carelli, Garret Stuber and Michael Heien monitored the release of dopamine over amazingly brief, 100-millisecond intervals -- about one-third the time the eye takes to blink and some 200 times faster than has ever been done before.
Working with rats trained to press a lever to receive a cocaine "reward," the team found the chemical trigger both precedes and proceeds from the pursuit of gratification.
The researchers measured dopamine release in the nucleus accumbens, a brain region implicated in functions ranging from motivation and reward to feeding and drug addiction. They observed a brief dopamine burst seconds before the animals approached the lever. In rodents taught to associate a flash of light and a tone with a forthcoming "hit," the audiovisual cue itself was sufficient to get the dopamine flowing.
"Our work indicates that just the anticipation of receiving cocaine may cause significant increases in dopamine levels that may control drug-taking behaviors," said Carelli, associate professor of psychology.
The dopamine levels continued to rise as the rodents closed in on the lever and pressed, peaking just after the animals got their "fix." No such rise in dopamine level was detected in control animals not trained to get cocaine on demand, Phillips said.
"As a rat chases its tail, drug addicts may suffer a similar vicious circle of priming and reward controlled by these dopamine signals," Self explained. "Therapies aimed at preventing one or both of these dopamine signals could be effective treatments for addiction."
The irresistibility of the signals' effect is exemplified by the inability of food addicts to stop with just one bite, scientists said.
"Chocolate lovers whose cravings are strongly enhanced by tasting just a small morsel often experience this priming effect," Self told UPI. "The initial taste whets the appetite for more, explaining the brief shelf life of an open chocolate box."
In suggesting the same chemical that produces euphoria with cocaine also can trigger yearning for the drug, the study raises the prospect of new treatments, scientists said.
"Pharmacological or behavioral treatments that blunt this dopamine pulse, without completely blocking all dopamine function, could be one way to prevent drug craving," Self said.
The research was funded by the National Institute on Drug Abuse.
Copyright 2003 by United Press International.