Functional Imaging of Craving : Part 6

by National Institute of Health

(Page 6 of 6)

Studies of the activities of individual dopamine neurons in the monkey brain in response to certain stimuli have helped generate a framework for understanding the neurophysiology of craving and may provide suggestions for the design of future imaging studies. In those studies, animals repeatedly were exposed to arbitrary stimuli (colored lights) that predicted the opportunity to gain a reward. When the stimulus initially was paired with a reward, it rapidly elicited a burst of activity in the dopamine-releasing neurons of the midbrain. Thus, it appears that dopamine-releasing neurons provide a signal indicating the presence of an important new association to be learned between a stimulus and a subsequent reward. With continued pairings of the stimulus and the reward, however, the dopamine-releasing neurons stop responding, indicating that those neurons do not react to stimuli with a well-established, consistent relationship to a reward. In other words, once an association is learned, no further dopamine activity is required to maintain that connection. In fact, if dopamine activity indicates that the organism must learn a new association between a stimulus, a behavior, and a reward, then responses of dopamine-releasing neurons in familiar, unchanging situations might even be counterproductive.

Both alcohol and cocaine increase dopamine concentrations throughout the various basal ganglia-thalamocortical circuits that have been implicated in craving in the studies reviewed in this article. Consequently, both drugs should put a person's brain into a state similar to the state that occurs when a person makes the initial connection between a stimulus or behavior and a desired reward. Such a state may be both pleasant and arousing and therefore may encourage further drug consumption (is reinforcing). In addition, the elevated dopamine concentrations should prime the person to associate the stimuli preceding alcohol or cocaine use (certain objects, places, people, thoughts, or feelings) with the pleasure experienced when the drug is taken. Thus, when those stimuli are encountered again, they should initially elicit a burst of activity in the dopaminereleasing neurons, thereby leading to anticipation of the reward and AODseeking behavior. This scenario corresponds to appetitively motivated craving. What happens, however, when an alcoholic encounters stimuli associated with alcohol use in a situation in which he or she cannot drink? The experiments in monkeys mentioned earlier also demonstrated that when a stimulus which previously had been paired with a reward stopped predicting that reward, appearance of that stimulus soon began to elicit a decrease in dopamine activity. This observation leads to two questions. First, if a burst of dopamine neuron activity signals the organism to learn an association, does a decrease in dopamine neuron activity indicate that a connection must be "unlearned"? Second, if a burst of dopamine neuron activity leads to a pleasant or arousing state, does a decrease in dopamine neuron activity lead to a dysphoric state, perhaps akin to frustration? Although the answers to those questions are unknown, the questions themselves suggest that the model of craving underlying the design of the studies reviewed here is too simplistic.

To date, all functional imaging studies have treated craving as a state characterized by only one pattern of behaviors or emotions. The studies by Schultz and the resulting questions, however, indicate that the desire to drink elicited by a cue or low alcohol dose in a situation in which the subject knows that more alcohol is available likely differs from the desire to drink elicited in a situation in which further alcohol consumption is impossible. Although subjects in one of the studies reviewed here were allowed to use cocaine after the cue exposure and scanning were completed, no study has systematically examined the effect of the perceived availability of the drug on brain states associated with craving.

The Future of Functional Imaging of Craving

Although the imaging studies discussed in this article have begun to shed light on the brain regions involved in craving, future studies should address several additional issues. First, researchers should design studies that can distinguish the effects of appetitive and aversive motivation. For example, experiments could compare the effects of craving on brain activity under conditions in which the subject knows that AODs will or will not be available.

Second, imaging studies in healthy people without AOD addiction should attempt to identify patterns of brain activity generally associated with appetitive and aversive motivation (not associated with AODs). The results of such studies could be compared with the patterns of brain activation found during craving for AODs, thereby enabling researchers to understand craving in the context of how the brain deals with motivation in general.

Third, although this review has focused on dopamine, researchers know that many other neurotransmitters are involved in motivational processes. Thus, the neurotransmitters gamma-aminobutyric acid (GABA), glutamate, and opiate peptides - and, perhaps, serotonin - all help mediate the reinforcing properties of alcohol. Once the nature of the brain states associated with craving has been characterized in more detail, it may be possible to explore systematically how drugs that selectively affect specific neurotransmitters can modify those brain states.

In summary, the concept of craving, which has its origin in popular psychology, may not correspond to unitary brain states observable with functional imaging techniques. By carefully designing and analyzing functional imaging studies, however, researchers may be able to determine whether it would be more useful for researchers to divide the process of craving into two or more components. If functional imaging is to be more than colored pictures that humans use to convince themselves that psychological constructs have a physical reality in the brain, researchers must be able to use this approach to test hypotheses and change their models of how the mind works.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.