Nicotine becomes habit-forming by hijacking the brain’s pleasure pathways. But to better treat nicotine addicts, scientists need to figure out precisely how it does so. University of Chicago researchers led by postdoctoral student Huibert Mansvelder appear to have unlocked much of the mystery.

One way most drugs cause addiction when they hit the brain is by stimulating certain cells to make dopamine, the biochemical most crucial to the experience of pleasure. But according to the researchers, smoking does a good deal more than that. Using rats, they discovered that the first time a brain is subjected to nicotine, the substance not only stimulates brain cells to make more dopamine, but also interferes with the brain’s ability to regulate the chemical. Consequently, a smoker’s high lingers as long as 45 minutes after the nicotine has disappeared from the bloodstream. The smoker experiences a runaway feel-good sensation that the brain records in its reward center and craves again and again.

Novice smokers, however, rarely become addicted after only the first few puffs. It’s repeated exposure to the substance that causes cravings. So the next step, say researchers, is to study how persistent smoking alters the brain’s ability to rein in dopamine and how that ultimately contributes to nicotine addiction-a find that will offer new targets for antiaddiction drugs.