Study Suggests Molecular Basis for Urge to Smoke

When cigarette smokers first stop smoking the number of nicotine receptors in the brain is significantly higher when compared to non-smokers, which may explain why it is so tough to quit, according to a study by Yale School of Medicine researchers published this week in the Journal of Neuroscience.

The study funded by the National Institutes of Health (NIH) is believed to provide the first direct evidence in living smokers that the densities of the most common nicotine brain receptors are higher during early smoking abstinence. It also suggests that the number of receptors is related to the urge to smoke to relieve withdrawal symptoms.

“Millions of Americans want to quit smoking, but few are successful,” said Nora Volkow, M.D., director of the National Institute on Drug Abuse, which is part of the NIH and helped support the study. “This study provides new evidence about the lingering impact of tobacco addiction that may help researchers develop more effective smoking cessation and relapse prevention therapies.”

Julie Staley, associate professor in the Departments of Psychiatry and Diagnostic Radiology and lead author of the study, said nicotine craving is an important factor associated with relapse. “This study paves the way for determining whether medications normalize the number of receptors and why some smokers, such as women and those with neuropsychiatric disorders, have more difficulty quitting smoking,” she said.

Nicotine acts like a key in the brain, inserting itself into the nicotinic acetylcholine receptors (nAChR) to initiate a cascade of chemical changes in the brain, all of which contribute to the effects of smoking a cigarette. Staley said the team measured nicotine receptors in the brain of living smokers to see how the receptors adapt in response to the repeated stimulation that occurs every time a smoker smokes a cigarette. The receptors were measured using a SPECT camera and a radiotracer that labeled the nicotine-binding site on nAChRs.

Sixteen smokers refrained from smoking for at least four days before undergoing imaging. The brain scans of the 16 smokers were then compared to scans of 16 nonsmokers of similar ages and gender. The scans showed that nicotine receptors were significantly higher in several brain areas, including the striatum, throughout the cerebral cortex, and the cerebellum.

“Among other studies, researchers are looking at how nicotine replacement therapy or low nicotine cigarettes relieve withdrawal symptoms, craving, and nicotine effects on attention, memory and concentration,” Staley said.

Staley is an investigator with the Transdisciplinary Tobacco Use Research Center at Yale (TTURC) and the Center for Nicotine and Tobacco Use Research at Yale (CENTURY). TTURC is one of seven research centers nationwide conducting a diverse spectrum of transdisciplinary tobacco-related research. The Yale TTURC was created with grants from the National Cancer Institute, the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and The Robert Wood Johnson Foundation.

Journal of Neuroscience 26(34): 8707-8714 (August 21, 2006)

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