PET lights up brain circuitries of tobacco dependence

PET can identify the brain receptors most vulnerable to nicotine absorption, measuring how just a single cigarette puff can drive the desire for smoking, according to National Institute on Drug Abuse researchers. Resulting data may lead to more effective treatments to help smokers quit.

Smokers everywhere express a strong desire to quit the habit, but very few succeed. Data show that fewer than half can permanently stop smoking even after extensive treatment. Now study findings suggest that typical smokers need to have brain nicotine receptors almost completely saturated throughout the day, and this need creates an almost uncontrollable urge to keep smoking, said NIDA director Dr. Nora D. Volkow.

"This study illustrates the powerfully addictive impact of even small amounts of nicotine," she said.

Dr. Arthur Brody and colleagues at the University of California, Los Angeles David Geffen School of Medicine used PET to observe nicotine distribution in the brains of 11 smokers. Participants had to choose between not smoking, having one puff or three puffs, finishing one full cigarette, or smoking until their craving was satisfied.

The investigators measured craving using the Urge to Smoke scale, which assesses responses to 10 craving-related questions. They also used MRI to help localize brain regions on the PET scans.

The researchers found that the amount of nicotine contained in just one puff can occupy about 30% of the brain's most common type of nicotine receptors, while three puffs of a cigarette can occupy about 70% of them.

The smoker becomes temporarily satisfied when nearly all of the receptors are occupied, usually after smoking at least two and one-half cigarettes. Soon, however, this level of satiation wears off, driving the smoker to continue smoking throughout the day to satisfy the cravings. The study was published in the August 2006 issue of the Archives of General Psychiatry.

"We saw on our PET scans that the radiotracer 'disappeared' over time as the nicotine receptors became occupied by nicotine from cigarettes," Brody said.

The scientists found that the highest levels of nicotine binding occurred in the thalamus, brain stem, and cerebellum. Results of another recently published NIDA-supported study suggest that a portion of the cerebellum called the vermis may be a key factor in modulating the brain's dopamine and reward systems. The vermins may be more involved in drug abuse and addiction than previously thought.

"Although craving was reduced only with near-total occupancy of these receptors, there remains the question of whether other, less common types of nicotine receptors are equally important in tobacco dependence," Brody said. "This is an important area of focus for future research."

A more complete understanding of how nicotine affects the brain can help scientists develop better therapies for people looking to quit. Since even low levels of nicotine exposure result in substantial occupancy of these receptors, additional research needs to address the impact of secondhand, or environmental, tobacco smoke on nicotine craving, Volkow said.

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