Findings suggest important differences among smokers in brain responses that underlie the smoking habit

Not all smokers are alike when it comes to cravings, and a new study conducted by researchers at Duke University Medical Center suggests the difference may lie in their brains' sensitivity to drug cues.

The researchers found that smokers who report a greater urge to smoke after a period of abstinence also exhibit stronger brain activity after viewing smoking-related images, such as others smoking or a pack of cigarettes.

Smokers who noted fewer cravings showed stable brain responses to the same drug cues, despite hours of deprivation.

The findings suggest important differences among smokers in brain responses that underlie the smoking habit, the researchers said. What's more, they added, such brain scans may yield diagnostic tests for predicting which smokers will benefit most from particular quitting methods.

The team reported its results in an article in the journal Neuropsychopharmacology that is now online and which will be published in print in a forthcoming issue. The research was supported by the National Institute on Drug Abuse.

"Our results suggest that not all smokers are the same; they don't all respond to drug cues in the same way," said Joe McClernon, Ph.D., a clinical psychologist at the Duke Center for Nicotine and Smoking Cessation Research and lead author of the study. "Furthermore, how they respond depends on the degree to which deprivation leads them to crave cigarettes.

"Smokers' responses to drug cues are important in maintaining the smoking habit and also serve as strong triggers to return to smoking for those who have quit," McClernon added. "As we begin to understand the underlying brain processes, we may discover new methods for manipulating those responses to better help smokers quit."

While scientists have thought that nicotine is the primary agent responsible for cigarette addiction, recent evidence suggests that conditioned responses to sensory cues also play an important role, McClernon said. Brain imaging studies of smokers have found increases in brain activity in response to smoking-related images in areas associated with attention, motivation and reward. However, those studies examined smokers only after a period of overnight deprivation from smoking.

To further explore this phenomenon, the researchers examined smokers' brain responses in attention, motivation and reward regions after a period of overnight abstinence from smoking and after smoking as usual. While their brains were scanned, smokers saw smoking-related pictures and pictures of everyday people and objects, such as a stapler or door knob. The researchers also asked participants to rate the intensity of their craving for cigarettes. The researchers scanned the subjects' brains using functional magnetic resonance imaging, in which harmless magnetic fields and radio waves are used to produce images depicting blood flow in brain regions. That blood flow reflects brain activity in those regions.

As a group, smokers' brain responses to drug cues remained stable regardless of the duration of time since their last cigarette, found the researchers. However, further analysis revealed that those smokers who reported more intense cravings after deprivation also exhibited heightened sensitivity to smoking-related images compared to those who craved cigarettes less.

"These findings are exciting because we are beginning to find out which brain regions may be involved in cigarette craving," said Jed Rose, Ph.D., director of the Duke Center for Nicotine and Smoking Cessation Research.

Smokers who exhibit greater sensitivity to environmental cues might have particular difficulty quitting smoking and may also be particularly prone to relapse, McClernon said. While experts advise that all people attempting to quit avoid situations or objects that remind them of smoking, the new results suggest that such measures may be particularly important for some smokers, he said.

The Duke team is now examining methods that may help break the connection between cigarette cues and brain activity as a means of boosting quitting success rates. For example, methods in which people switch to nicotine-free cigarettes prior to smoking cessation may help extinguish the connection between smoking and the rewarding affects of nicotine, thereby easing the brain's sensitivity to drug cues.

Collaborators on the study included F. Berry Hiott and Scott Huettel, both of Duke.