Study exploring gender differences in smoking could have bigger implications

A new gender-based study of smoking that offers the first practical application of a technological advance for documenting dopamine response appears to have several potentially compelling implications for future addiction research. The Yale University study, which lends further insight to why men and women respond differently to smoking and to cessation treatments, could reinvigorate development of cessation therapies while also having applicability to other substance addictions.

“We're hoping that these patterns of dopamine release that we weren't able to see before are relevant to all types of addiction,” says Evan D. Morris, PhD, associate professor of diagnostic radiology, biomedical engineering and psychiatry at the university and senior author of the study.

The study's origins lie in some truths about smoking that nevertheless have lacked a deeper understanding. Men and women appear to smoke for different reasons, with men generally more reinforced by nicotine. Current favored treatments for smoking cessation, such as nicotine replacement therapies, tend to be less effective for women. Yet because researchers have not been able to grasp the neurobiological reasons for these observed differences, treatment advances for smoking cessation have largely been stuck in neutral.

Yet for the past several years, Morris and colleagues have been studying a way to more precisely identify patterns of neurotransmitter release through PET (positron emission tomography) scans. Morris says his interest in this area grew out of his experience working at the National Institute on Drug Abuse (NIDA), where he was exposed to discussions about the speed at which neurotransmitter activity peaks in the brain. “I started to think, 'Is there any speed information embedded in PET images?'” he says.

The technology that was practically applied for the first time in this smoking study essentially allowed for the stripping away of all other contributors to the PET image, thus isolating the effect of dopamine. The technology creates dynamic images that for the first time allow researchers to observe timing information about neurotransmitter activation. This can prove to be an especially important factor in smoking research because the brain's response to a smoked cigarette is rapid and brief. “The response to smoking doesn't even last for the duration of the scan,” Morris says.

Yale researchers were able to use this new method of PET analysis to characterize the effects of smoking on the mesolimbic dopamine system, in a group of eight male and eight female smokers.

Study results

In the study, published Dec. 10 in The Journal of Neuroscience, researchers created “movies” that depicted the effects of changes in neurotransmitter concentration in the 16 nicotine-dependent subjects; each smoked cigarettes during the PET scan. The researchers examined response in areas of the striatum.

They primarily found significantly more and faster smoking-induced dopamine activation in the ventral striatum among the male smokers. This finding is in line with the theory that men smoke for the reinforcing effect of nicotine, as the ventral striatum governs reward processing and drug response.

Activation in the ventral striatum was largely absent in the female smokers, but a secondary finding of the study concluded that rapid dopamine response in women occurred in an area of the dorsal striatum, a region that has been associated with habit formation. This reinforces the notion that women in general smoke not for the reinforcing effects of nicotine, but for reasons such as relieving negative mood and stress. These findings also offer more concrete evidence behind why nicotine patches and other replacement therapies don't work as well for women, and this can possibly help identify alternative targets for therapies.

“We hope to see if we can get medications to modulate the dopamine response,” says Kelly Cosgrove, PhD, associate professor of psychiatry, diagnostic radiology and neurobiology at Yale and lead author of the study. “Maybe we can garner additional interest in the industry in developing medications.”

Morris says he sees numerous other potential applications of the new technology to inform the treatment of addictions. “There are a number of natural ways to go with this,” he says. “For example, what would the movies look like if a person is being successfully treated for addiction? This ultimately could be a way of testing for the efficacy of certain medications.”