Author: Nora Volkow, Director, National Institute on Drug Abuse
Drug craving triggered by cues, such as the sight, smell, and other sensory stimuli associated with a particular drug like cocaine, is central to addiction and poses an obstacle to successful therapy for many individuals.
Today, using sophisticated brain-imaging techniques, we can actually see increases in specific brain activities that are linked to this experience.
If we can understand the mechanisms related to cue-induced drug craving, we can develop more effective treatment strategies to counteract it.
In this talk we will report on a brain-imaging study that evaluated how levels of the neurotransmitter dopamine changed in various parts of the brain when cocaine-addicted subjects were presented with drug cues.
The study also evaluated the relationship of these changes to the research subjects' subjective desire for the drug.
We will also compare these findings to those we had previously obtained in food-deprived subjects exposed to food cues, highlighting the differences and similarities in the responses of the dopamine system of an addicted person and that of a healthy control subject under conditions of food deprivation.
Previous research conducted by our group and others has shown that all addictive drugs increase the level of dopamine ? a neurotransmitter, or chemical messenger, associated with feelings of reward and pleasure ? in a part of the brain known as the nucleus accumbens.
This acute reaction in the brain's “pleasure center” is believed to underlie the reinforcing effects of addictive drugs, but does not explain the intense desire and compulsive use that occurs when addicted subjects are exposed to drug cues rather than the drug itself.
Moreover, we had shown that, in cocaine abusers, the ability for a stimulant to increase dopamine was blunted (50 percent lower than in controls).
We have now extended these studies to alcoholics and will be presenting new data showing that, in alcoholics, there is also a marked reduction in dopamine in response to a stimulant drug in the ventral striatum (70% lower than in controls).
Since the ventral striatum is the area of the brain involved with pleasure and motivation, this could underlie the dysphoria and lack of motivation observed in alcoholic subjects.
To probe the role of dopamine in cue-induced craving, we measured dopamine levels in various parts of the brain in 18 cocaine addicts as they watched a “cocaine-cues” video (featuring people buying and using cocaine), and the same 18 subjects as they watched a “neutral” video of natural scenery.
We also asked the subjects to rate their level of craving while watching both videos, and assessed the severity of their addiction using a standard cocaine craving scale.
Dopamine levels were measured indirectly using positron emission tomography (PET) scanning at Brookhaven National Laboratory's Center for Translational Neuroimaging. Each subject was injected with a radiotracer designed to bind to dopamine receptors in the brain.
During scanning, the PET camera picks up the signal from any bound radiotracer so that levels of tracer bound to receptors can be compared with levels in the blood. As the body's natural dopamine levels rise, this “endogenous” dopamine competes with the tracer for binding sites, so less radiotracer can bind to the receptors.
Therefore, the lower the bound tracer signal, the higher the concentration of endogenous dopamine.
Compared with the neutral video, the cocaine-cues video triggered a significant increase in dopamine in the dorsal striatum, a part of the brain involved in experiencing desire or motivation.
The changes in dopamine were associated with the level of craving reported by the subjects and were largest in the most severely addicted subjects.
This finding is consistent with previous animal studies that have suggested a role for the dorsal striatum in cue-induced craving.
In those studies, neutral stimuli such as a particular cage environment that had been paired with a drug during “training” sessions later triggered a dopamine increase in both the nucleus accumbens and the dorsal striatum, a response that was correlated with drug-seeking behaviors in the animals.
The finding is also consistent with earlier Brookhaven research documenting dopamine increases in the dorsal striatum induced by exposure to food. In that study, healthy subjects were allowed to observe and smell their favorite foods, but not eat them; the more the subjects desired the foods, the higher their dopamine levels went.
Finding this same association between dorsal striatum dopamine levels and cravings for food and drugs suggests that, in the human brain, drug addiction engages the same neurobiological processes that motivate food-seeking behaviors triggered by food-conditioned cues.
This research suggests that compounds that could inhibit cue-induced striatal dopamine increases would be logical targets for medication development to treat cocaine addiction.
Abstract of presentation at BNL Addiction Symposium at the AAAS Annual Meeting, February 16, 2007
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