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  Research
Smoking alters brain's 'feel good' chemistry


Smokers often say that lighting up a cigarette can calm their nerves, satisfy their craving and help them relax.

Now, a team of scientists from U-M is reporting evidence of why that might be: Smoking produces major changes in the flow of "feel good" chemicals between brain cells, both temporarily and long-term. And those changes in flow match up with changes in how smokers say they feel before and after smoking.

It's the first time smoking has been shown by positron emission tomography (PET) imaging to affect the human brain's natural system of chemicals called endogenous opioids, which are known to play a role in quelling painful sensations, heightening positive emotions and creating a sense of reward. It's the same system that is stimulated by heroin and morphine.

The research team from the Medical School presented the results Oct. 26 at the annual meeting of the Society for Neuroscience.

The results come from a pilot study involving a small group of young male pack-a-day smokers and non-smoking comparison subjects. Despite their study's small size, the researchers say the surprisingly large effect on opioid levels they found suggests a promising road for further discovery. That may lead to better understanding of why smoking affects people the way it does—including the mystery of why it often is so hard to quit, despite tobacco's many health dangers.

"It appears that smokers have an altered opioid flow all the time, when compared with non-smokers, and that smoking a cigarette further alters that flow by 20 to 30 percent in regions of the brain important to emotions and craving," says David J. Scott, a graduate student in the Neuroscience Program who presented the results. "This change in flow as seen on a brain scan correlated with changes in how the smokers themselves reported feeling before and after smoking."

Scott, his professors and his colleagues made the findings using a type of brain scanning called PET imaging. This allowed them to literally see activity in the endogenous opioid system when the study participants first smoked a special cigarette with almost no nicotine, and then smoked a regular cigarette. Before, during and after the scans, the participants rated how relaxed, alert, sick and nervous they felt, and how much they were craving tobacco.

Now the team is studying the interaction of dopamine and opioids in the brains of smokers and non-smokers. They also hope to look at underlying genetic differences that might explain variations between people in response to nicotine—and perhaps differences in how easily people become addicted to cigarettes or quit smoking.

"The interaction of tobacco, and especially nicotine, with brain chemistry is a fascinating area that we're just beginning to understand, especially when it comes to correlating neurochemistry with behavior," says study leader Dr. Jon-Kar Zubieta, a psychiatrist and neuroscientist at U-M. "Just as with the 'hard' drugs of abuse, such as heroin and cocaine, the phenomena of pleasure, addiction, increased tolerance and craving from tobacco are firmly rooted in neurochemistry."

Adds veteran tobacco researcher and U-M active emeritus pharmacology professor Ed Domino, "Nicotine is necessary, but not sufficient, to maintain smoking behavior. Pure nicotine is a weak reinforcer compared to other drugs of abuse such as alcohol, amphetamines, cocaine and opiates such as heroin. One can buy over-the-counter nicotine gum and nicotine patches from a pharmacy and not become addicted. Tobacco addiction also involves many other complex non-pharmacological factors such as psychological conditioning and social interactions. Pharmacology is only part of the complex story."

The research was funded by the National Institute on Drug Abuse, part of the National Institutes of Health. In addition to Scott, Zubieta and Domino, the research team included Lisong Ni, a research associate in Pharmacology, and Mary Heitzeg, a research fellow in the Department of Psychiatry and U-M Addiction Research Center. Zubieta is a member of the U-M Mental Health Research Institute and a director of the U-M Depression Center.

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