WASHINGTON, D.C. — The minty flavor added to menthol cigarettes might make it even harder for smokers to quit, new research shows.

Most smokers know they should quit. Unfortunately, the nicotine in tobacco is addictive. That makes quitting really hard. Scientists have known that it’s even harder for people who light up menthol cigarettes.

The question has been why, notes Brandon Henderson. He’s a neuroscientist in Pasadena at the California Institute of Technology, or Caltech.

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The answer, his team now finds, may have a lot to do with how menthol boosts the effect of nicotine on the brain. Repeated exposure to nicotine leads the brain to make more nicotine receptors — docking stations for the chemical on cells. These nicotinic receptors are proteins. And their role is to impact the brain’s pathways for a chemical known as dopamine (DOPE-uh-meen). Dopamine transmits signals in the brain. Some of those signals turn on centers that convey feelings of pleasure and rewards. Indeed, this feel-good chemical helps make smoking rewarding — and addictive.

To see how menthol might affect this system, Henderson and his Caltech teammates worked with special lab mice. One type of nicotinic receptor in the mice glows cherry red under fluorescent light. Another type glows bright green.

The researchers exposed these mice to menthol. (This chemical occurs naturally in spearmint and peppermint.) Then the experts focused in on a part of the midbrain. It’s known as the ventral tegmental area, or VTA. The VTA plays a role in emotion, motivation and addiction.

Mice exposed to menthol had more of both types of nicotinic receptors than did unexposed mice. The increase was similar to that produced by nicotine, the scientists found.

“This goes to show that menthol is not simply an inert flavoring in cigarettes,” says Henderson. “It has some effects in the brain.” Henderson presented his team’s results here on November 16 at the annual meeting of the Society for Neuroscience.

“The most significant finding from Dr. Henderson’s study is that chronic exposure to menthol can change the number of receptors for nicotine in the brain to a similar extent that nicotine can,” says Marina Picciotto. A neuroscientist at Yale University in New Haven, Conn., she did not work on the new study.

“Menthol may increase the addictive properties of nicotine at the molecular level,” Picciotto concludes. Still, she cautions, scientists need to see if that molecular action affects behavior. And to be sure menthol works the same way in people, she says, “We need more information from human subjects.”

Yolks yoke in folks who smoke

Results from a second study presented at the meeting suggest that adding a foul odor to cigarette smoke could help people cut back on smoking. But the idea may work best if people sleep through the stinky experience.

Anat Arzi is a neuroscientist at the Weizmann Institute of Science in Rehovot, Israel. Earlier, she and other researchers had shown that people can learn to link some experiences as they sleep.

Arzi now wondered whether that type of learning might influence waking behaviors, such as smoking. To find out, she and other scientists exposed groups of smokers to different odors. One stinky stew mixed together the stench of cigarette smoke and rotten eggs. Another paired the smells of smoke and rotten fish.

Researchers told everyone participating in the study that the experience might help them stop or cut back on smoking. But only those smokers who smelled the foul combos while awake knew what just what the experiment involved.

Other smokers smelled those odors only while they slept. Unlike loud noises or bright lights, odors seldom wake people up.

Some volunteers in a study in Israel were exposed to a mix of foul odors and cigarette smoke during different stages of sleep. These tests showed that stinky sleep smells might help people cut back on smoking. Courtesy of Michael Cooper.

One group smelled the nasty smells during Stage 2 sleep. That’s the type that occurs most of the night. Others experienced it during rapid eye movement (REM) sleep. Most dreams occur during REM sleep. The study also included control groups — people who slept while no smells scented the air.

Over the following week, people in each group tracked how much they smoked. People exposed to noxious smells during Stage 2 sleep smoked significantly less than before.

“The reduction was around 30 percent,” Arzi reported. That group smoked significantly fewer cigarettes on each day during the week, too.

In contrast, people treated during REM sleep smoked significantly less on only two of the next seven days. So here, the effect did not seem to last all week. And the group that had been awake when exposed to the odors? They showed no change in their smoking habits.

“In other words, sleep learning can influence later awake behavior,” Arzi concludes. The Journal of Neuroscience published the study by Arzi and her colleagues in November.

“The most significant finding of Dr. Arzi’s study is that pairing a nasty odor with the smell of a cigarette can reduce the amount of smoking for several days — and that this only happens during sleep,” says Picciotto, the Yale neuroscientist.

Arzi’s study paired odors for just one night. It then tracked smoking for only one week afterward. A next step, says Picciotto. “would be to see how long the effect lasts.”

That’s important, because tobacco addiction is a major health problem. In the United States alone, cigarette smoking leads to roughly one in five early deaths each year. That statistic comes from the National Institute on Drug Abuse in Rockville, Md. What’s more, it notes, roughly 85 percent of smokers fail when they try to stop on their own.

For that reason, scientists need to learn all they can about causes and treatments for tobacco addiction. The new studies on smoking and smelly substances could one day help all of us breathe easier.

Power Words

addiction The uncontrolled use of a habit-forming drug or uncontrolled and unhealthy habit (such as video game playing or phone texting). It results from an illness triggered by brain changes that occur after using some drugs or engaging in some extremely pleasurable activities. Persons with an addiction will feel a compelling need to use a drug (which can be alcohol, the nicotine in tobacco, a prescription drug or an illegal chemical such as cocaine or heroin), even when the user knows that doing so risks severe health or legal consequences. (For instance, even though 35 million Americans try to quit smoking each year, fewer than 15 out of 100 succeed. Most begin smoking again within a week, according to the National Institute on Drug Abuse.)

chronic A condition, such as an illness (or its symptoms, including pain), that lasts for a long time.

control A part of an experiment where nothing changes. The control is essential to scientific experiments. It shows that any new effect must be due to only the part of the test that a researcher has altered. For example, if scientists were testing different types of fertilizer in a garden, they would want one section of to remain unfertilized, as the control. Its area would show how plants in this garden grow under normal conditions. And that give scientists something against which they can compare their experimental data.

dopamine A neurotransmitter, this chemical helps transmit signals in the brain.

fluorescent Capable of absorbing and reemitting light. That reemitted light is known as a fluorescence.

inert Inactive or having no chemical or physical effects.

neuroscience Science that deals with the structure or function of the brain and other parts of the nervous system. Researchers in this field are known as neuroscientists.

neurotransmitter A chemical substance that is released at the end of a nerve fiber. It transfers an impulse to another nerve, a muscle cell or some other structure.

nicotine A colorless, oily chemical produced in tobacco and certain other plants. It creates the ‘buzz’ effect associated with smoking. It also is highly addictive, making it hard for smokers to give us their use of cigarettes. The chemical is also a poison, sometimes used as a pesticide to kill insects and even some invasive snakes or frogs.

nicotinic receptors A group of brain proteins that affects the signaling of dopamine. Repeated exposure to nicotine leads to more of these receptors in particular areas of the brain.

REM sleep A period of sleep that takes its name for the rapid eye movement, or REM, that occurs. People dream during REM sleep, but their bodies can’t move. In non-REM sleep, breathing and brain activity slow, but people can still move about.

ventral tegmental area Part of the midbrain. It plays an important role in thinking, motivation, emotions and addiction.