Chicago ? Working to unravel a long-standing puzzle of cigarette addiction, University of Chicago researchers have discovered why smoking is uniquely pleasurable and why nicotine has such ferociously addictive powers.

Published today in the scientific journal Neuron, the research shows that nicotine not only stimulates pleasure in the brain’s reward center but has the unique ability to neutralize the “off-switch” that usually throttles down good feelings quickly.

The finding provides major clues to understanding the complex process by which the brain becomes addicted to nicotine and opens new approaches to developing drugs to block nicotine’s power to hijack the brain.

For the 2,000 teen-agers a day who become regular smokers, the new evidence helps to explain how a single cigarette quickly teaches the brain cells to crave nicotine.

And for the more than 30 million American smokers who try to quit smoking each year and fail, the finding shows why breaking the habit is so hard.

The University of Chicago’s Daniel S. McGehee and his colleagues showed how nicotine from a cigarette produces a high that can last up to an hour.

It does so first by quickly turning on the pleasure chemical dopamine in the brain’s reward center, something scientists have known for several years. But the dopamine surge ends quickly, and researchers couldn’t figure out what caused nicotine’s long-lasting high and its subsequent ability to induce addiction.

McGehee’s finding shows for the first time that nicotine also acts on a group of regulatory cells whose job is to stop the dopamine high. With this control mechanism temporarily disabled, the reward system continues to operate out of control long after it should have been shut down.

The result is a runaway feel-good sensation that the brain commits to its memory bank as something it wants more of.

“This gives an explanation for why the long high happens,” said Dr. Glen Hanson, acting director of the National Institute on Drug Abuse. “It’s a combination of tolerance happening to several systems at the same time. When you sum everything up, you get an enhancement of the dopamine pleasure pathway.”

“Nicotine acts as if it’s reinforcing a behavior that should be rewarded,” said John Dani, a Baylor College of Medicine neuroscientist who was one of the first to show nicotine’s effect on dopamine. “The brain is fooled into thinking that nicotine is a proper participant in life.”

An estimated 57 million Americans smoke, which is linked to more than 400,000 deaths annually from cancer, heart attacks, strokes and emphysema. Smoking is the nation’s most preventable cause of death and disease.

A cigarette contains about 10 milligrams of nicotine. About 1 to 2 milligrams get into the blood stream and hit the brain’s reward center within 10 seconds after inhalation.

An average smoker takes 10 puffs per cigarette over a five-minute period. In a person who smokes a pack a day, the brain gets 200 hits of nicotine.