Sep. 30, 1997 Using a state-of-the art imaging technique, researchers at the Massachusetts General Hospital (MGH) have shown, in greater detail than before, how specific areas of the human brain react to cocaine, distinguishing patterns of activation associated with feelings of euphoria and craving among addicts. Their report, appearing in the September issue of Neuron, reveals that a much broader range of brain structures is involved in the cocaine "rush" than previously suspected and that the role of brain areas long thought to be involved in making cocaine rewarding and addictive is more complex than previously believed.
"This study gives us a detailed picture of cocaine's effects on brain circuits involved in both aspects of the reward system: reinforcement, which refers to an immediate positive or pleasurable reaction, and incentive, which in this context means motivation to repeat an activity,"says Hans Breiter, MD, a member of the MGH Radiology and Psychiatry Services and first author of the study. Much current understanding of how drugs like cocaine affect the brain has come from animal studies that correlated brain activity with observed behaviors, like pressing a lever to receive additional doses of drugs. But animals cannot report the kinds of subjective, emotional reactions humans experience and describe by terms such as "rush," "high," "low" and "craving." The current study supports previous animal observations of how the brain responds to cocaine and provides much greater detail regarding reactions of specific, tiny structures and how they relate to the feelings of the cocaine user.
"Understanding how different circuits are activated during the different stages of drug use and withdrawal can help us design and monitor novel treatments," says Steven E. Hyman, MD, director of the National Institute of Mental Health. Previously a member of the MGH Psychiatry Service, Hyman also is senior author of the Neuron paper.
In studying the reaction of the brain to cocaine, the reseachers used functional magnetic resonance imaging (fMRI), a technique largely developed at the MGH. Using fMRI, areas of increased brain activity, characterized by increased levels of oxygen in the blood, can be superimposed on detailed images of brain structures. Functional MRI scans were made of 10 volunteer participants - all of whom were carefully selected cocaine addicts - as they received cocaine injections and for 13 minutes following the injection. At 15-second intervals throughout the testing period - starting 5 minutes before the injection - participants reported the extent to which they experienced feelings of rush, high, low or craving.
Results indicated that more than 90 areas of the brain showed increased activity in response to cocaine. Many areas associated with thought and emotion showed an immediate although brief response of increased activity, which was associated with reported feelings of "rush" and euphoria. Other areas showing an immediate response remained activated longer, extending into periods when participants reported feelings of craving. One of the most significant among these is the nucleus accumbens, believed to be associated with reward reinforcement. In addition, the area called the amygdala, also associated with the reward system, showed lower-than-normal activity, particularly during periods of reported craving.
The results suggest, the researchers believe, that while there are distinct areas involved in the various experiences of cocaine use, it is not simply a matter of turning certain structures on to produce a particular response. Instead the patterns of which areas are activated in what sequence and for how long seem to determine the feelings generated, particularly in the case of craving.
"Our observations regarding the nucleus accumbens were probably the most unexpected," says Breiter. "That area has been thought to be involved in reinforcement, so we expected it would be activated as part of the pleasurable rush/high experience. But its continuing high level of activation into the craving phase suggests that it also plays a role in incentive, the motivation leading to a change in behavior, which is key to the development of addiction." Alan Leshner, PhD, director of the National Institute on Drug Abuse, a primary funder of this research, says, "These studies suggest specific brain areas that might be targeted in developing new medications to either block individual aspects of cocaine's effects - like the rush versus the craving experience - or as broader treatments for cocaine abuse and addiction." Additional funding for this study was provided by the National Heart, Lung, and Blood Institute and the National Alliance for Research on Schizophrenia and Depression.
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