For some people, one cigarette is all it takes to become hooked on nicotine, while others are repelled by it.
Researchers in Canada have found a region in the brains of rats that may be the key to these differences.
By manipulating specific molecular doorways into brain cells called receptors, they were able to control which rats in the study enjoyed their first exposure to nicotine and which were repelled by it.
“Our findings may explain an individual’s vulnerability to nicotine addiction and may point to new pharmacological treatments for the prevention of it and the treatment of nicotine withdrawal,” said Dr. Steven Laviolette of the University of Western Ontario, who reported his findings in the Journal of Neuroscience.
Several studies have found that certain people are especially responsive to the effects of nicotine.
To each his own
One, published last October in the journal Pediatrics, found teens who felt relaxed after their first drags on a cigarette were far more likely to become addicted to smoking.
“During the early phase of tobacco exposure, many individuals find nicotine highly unpleasant and aversive, whereas others may become rapidly dependent on nicotine and find it highly rewarding,” Laviolette said.
To explore the difference, Laviolette and colleagues did a series of experiments on rats, which have brain structures similar to humans.
They zeroed in on two areas in the reward circuit of the brain called nucleus accumbens. They found specific receptors of the message-carrying chemical dopamine in the core and shell of the nucleus accumbens controlled whether the rats enjoyed or were repelled by nicotine.
When the researchers blocked two types of dopamine receptors — D-1 and D-2 — with drugs delivered to these areas of the nucleus accumbens, the rats experienced nicotine as a positive, rewarding experience.
“We were able to switch nicotine’s aversive effects to rewarding effects,” Laviolette said in a telephone interview.
Laviolette said “naturally occurring differences” in these receptors may account for why some people are more susceptible to nicotine addiction.
Perhaps more importantly, the researchers also were able to reverse this process, making the nicotine unpleasant in rats that had the equivalent of a “pack-a-day” nicotine addiction.
And they discovered that these areas of the brain played an important role in nicotine withdrawal after an addiction had developed.
By manipulating these dopamine receptors, they were able to ease some of the withdrawal symptoms, a finding that could be important in helping people quit smoking.
Laviolette’s team is now studying the molecular changes underlying these mechanisms, which will be important for drug makers, who would need to target these specific dopamine receptors with chemicals.
“If we can develop pharmacological treatments to target those regions, we can basically affect the development of nicotine addiction by controlling the brain’s perception of nicotine’s rewarding effects,” Laviolette said.