Nicotine addiction relies on brain receptors that have been difficult to fully study and characterize. Scientists at the University of Colorado in Boulder have demonstrated that an immunolabeling technique can effectively analyze receptor subunits.

Background: Nicotine’s effects on the brain are triggered upon its binding to nicotinic acetylcholine receptors, each of which consists of five subunits: two alphas, one beta, one delta and one gamma. Different combinations of these subunits produce different receptor subtypes, which may vary in their pharmacology, biophysical properties, and distribution. To more fully understand how to interfere with nicotine’s effects in the brain, scientists must first understand where these
different receptors are and how they work. Two of the most important subunits, a4 and b2, have been hard to study because current study methods can only locate the fully assembled receptor unit. Researchers wanted to know if an alternative strategy of immunolabeling (i.e., using antibodies to tag individual proteins), which has been fraught with
technical challenges, would be able to identify, map, and quantify separate subunits.

Study Design: Scientists at the University of Colorado worked with brain sections of mice genetically engineered to express particular a4 and b2 subunit combinations. Using a sensitive immunolabeling technique, they explored the
expression of the a4 and b2 subunits at both the gene and protein levels. Additional mice strains, missing the subunits under study, were used as controls.

What They Found: The two predominant nicotinic receptor subtypes (a4 and b2) were reliably detected using immunolabeling. Expression of the a4 subunit protein was almost universally dependent on b2, whereas most, but not all, b2 subunit protein expression was a4-dependent.

Comments from the Authors: Immunolabeling using specific antibodies offers a powerful approach for mapping the distribution of nicotine receptor subunits and can produce reliable quantitative results.

What’s Next: Similar studies can be designed to locate other nicotine receptor subtypes. In many cases, the antibody recognition sites are inside the cell membrane. It will likely take alternative biochemical approaches to uncover these less
accessible sites. A better understanding of receptor composition and function may eventually have important implications for developing interventions at the receptor level.

Publication: The study, led by Dr. Paul Whiteaker of the Institute for Behavioral Genetics at the University of Colorado, Boulder, with Dr. Jon Lindstrom of the University of Pennsylvania, was published in volume 499, number 6, pages 1016- 1038 (2006) of the Journal of Comparative Neurology.

NIDA NewsScan, August 22, 2007

Many smokers are reluctant to quit because of the perceived risk of gaining weight after smoking cessation. But new research from the first large, prospectively randomized dose-ranging study of naltrexone for smoking cessation suggests that low-dose naltrexone can reduce weight gain in smokers using nicotine patch therapy.

The 6-week study, conducted by researchers at Yale School of Medicine and the NIDA-supported Transdisciplinary Tobacco Use Research Center (TTURC), included 400 patients who smoked at least one pack of cigarettes daily. Patients were treated with a nicotine patch and were randomly assigned to receive placebo or one of three doses of naltrexone. The scientists found that continuously abstinent smokers who took the lowest dose of the drug—25 mg—gained significantly less weight (1.5 lbs.) than those who took placebo (4.2 lbs.). In comparison, smokers who took 50 mg of the drug gained 2.4 lbs., and those who took 100 mg of naltrexone gained 3.3 lbs. Of those who completed treatment, 48 percent of the placebo group achieved continuous abstinence, compared with 51 percent of the 25-mg group, 48 percent of the 50-mg group, and 72 percent of the 100-mg group. Given that there wasn’t one dose that was effective in both reducing weight gain and improving smoking abstinence over nicotine patch alone, the optimal naltrexone dose for an individual may depend on the greatest motivating factor.

Naltrexone is an opiate antagonist, meaning that it binds to the same receptors in the brain as natural chemicals that are part of the brain’s reward system. The Food and Drug Administration originally approved naltrexone for people who are trying to break their addiction to opiate drugs like heroin and morphine.

What it means: Many people who try to quit smoking are concerned about gaining weight. The study suggests that low-dose naltrexone in combination with the nicotine patch may be useful as a second-line treatment for weight-concerned smokers who are trying to quit. The scientists say the study results support further testing of the 100-mg dose of naltrexone for improving smoking cessation outcomes.

Dr. Stephanie O’Malley and her colleagues published their findings in the March 27, 2006 issue of the Archives of Internal Medicine.

NIDA NewsScan, May 19, 2006

Smokers with schizophrenia and related disorders take in more nicotine per cigarette than people without such mental illnesses, suggesting that such diseases have a neurobiological component that drives people to seek out the drug. This, in turn, indicates that effective treatment for tobacco addiction for people with schizophrenia might include nicotine replacement treatments that mimic smoking behavior.

Dr. Jill Williams and her colleagues at the University of Medicine and Dentistry of New Jersey (UMDNJ)–Robert Wood Johnson Medical School, the UMDNJ–School of Public Health Tobacco Dependence Program, and the University of California–San Francisco compared blood levels of nicotine and its primary byproduct in 81 schizophrenic smokers and 55 smokers without the mental disorder.

They observed that blood levels of nicotine and cotinine (a breakdown product of nicotine from cigarette smoke) were 1.3 times higher in the mentally ill participants despite smoking a similar number of cigarettes per day. They also found that there were no differences between the groups in their ability to metabolize nicotine and cotinine, suggesting that the higher levels in schizophrenia were from differences in their cigarette intake patterns. The research supports anecdotal reports that smokers with schizophrenia seem to take more or deeper puffs than other smokers. Smokers with schizophrenia have death rates that exceed that of the general population. Such individuals are at greater risk for death from smoking-related illnesses, such as cardiovascular disease and respiratory disease.

What it means: Smoking in schizophrenics appears to be linked to the unique neurobiological abnormalities of the disorder. Recognizing the differences in nicotine intake by schizophrenic smokers is important not only for developing more effective smoking cessation tools for people with schizophrenia, such as a nicotine nasal spray that provides high, intermittent doses, but also for providing additional insight into the nature of the disease.

The scientists published these findings in the November 2005 issue of Schizophrenia Research.

NIDA NewsScan, May 19, 2006

Having parents or friends who smoke, dropping out of high school, and trying cigarettes at a young age are among the factors that are linked to adolescents being more likely to become chronic smokers, according to new research supported in part by NIDA.

An analysis of a national sample of more than 14,000 young adults of different racial and ethnic backgrounds found that a number of common factors contribute to daily smoking and nicotine addiction among youth. Depression, however, was uniquely associated with addiction.

Finding cigarettes pleasurable when first trying them and being a “novelty seeker” were other factors associated with youth becoming chronic smokers. However, the researchers found some differences across racial/ethnic groups. Overall, minority youth were less likely than white youth to try cigarettes, become daily smokers once they did try cigarettes, and become addicted to nicotine once becoming daily smokers. Having parents and peers who smoke was associated with chronic smoking among white and Hispanic adolescents, but not African-Americans in the study. African-American youth appeared to be less influenced than whites by the models for smoking in their close interpersonal network.

What it means: A number of social, psychological, and biological factors predispose youth to become daily smokers or addicted to nicotine. Primary prevention and interventions that address the commonalities could be uniform, irrespective of race and ethnicity.

Dr. Denise Kandel and her colleagues at Columbia University and the New York State Psychiatric Institute published these findings in the February 2006 issue of the American Journal of Public Health.

NIDA NewsScan, May 19, 2006

Results of a recently published study suggest that psychiatrists tend to significantly underreport patients who smoke and undertreat their smoking problem. This finding, say the scientists who conducted the research, is important because psychiatric patients who smoke are likely to have greater psychosocial needs than those who do not.

Psychiatrists provided information on 1,752 patients, 280 of whom were reported to have a nicotine problem. Of these, only 27 had received treatment from the psychiatrists for nicotine addiction.

The data show that psychiatric patients who smoke are more likely to be males who are single, divorced, or separated; have low levels of educational achievement compared with nonsmokers receiving psychiatric treatment; and have significantly more co-occurring psychiatric disorders, such as schizophrenia and alcohol or other substance abuse.

What it means: Psychiatrists who routinely treat people who are nicotine-addicted should be more alert to the relationship between smoking and increased medical and psychosocial needs. Educational programs to raise the awareness of psychiatrists to diagnose and treat smoking problems are needed to alleviate this public health problem.

The study, led by Dr. Ivan Montoya of NIDA’s Division of Pharmacotherapies and Medical Consequences of Drug Abuse, was published in the October-December 2005 issue of the American Journal on Addictions.

NIDA NewsScan, May 19, 2006

Each year nearly half of all smokers attempt to quit smoking, but less than 5 percent are successful beyond 3 months to a year. Results from a new study by Dr. Dorothy Hatsukami and colleagues from the University of Minnesota Medical School suggest a new nicotine vaccine may be safe and effective in helping smokers who want to quit.

A total of 68 smokers randomly received a placebo or one of three doses of nicotine vaccine four times over 26 weeks. The researchers then observed the patients for an additional 38 weeks to monitor nicotine antibody levels, smoking behavior, and/or adverse side effects such as nausea, fatigue, or pain.

The scientists observed that nicotine antibodies (molecules that bind to nicotine, reducing its distribution to and its effects in the brain) increased in all nicotine vaccine groups. More patients who received the highest dose of vaccine achieved 30-day abstinence, and in a shorter amount of time, than those who received the other doses or placebo. Moreover, scientists found no evidence of withdrawal symptoms such as craving, irritability, or compensatory smoking (smoking more of a cigarette or puffing more often to increase nicotine intake). More than 90 percent of reported side effects were of mild or moderate severity. The most frequently reported events were upper respiratory tract infection, headache, cough, and inflammation of the nasal passages and throat. There were no observed differences in the frequency of these events among the four treatment groups.

What it means: Study participants who received the vaccine experienced none of the typical withdrawal symptoms commonly experienced by smokers. The nicotine vaccine may offer a promising new treatment alternative for smokers seeking to quit. Further research is needed to maximize the vaccine’s ability to diminish nicotine’s effects in humans.

Dr. Hatsukami and her colleagues published this study in the November 2005 issue of Clinical Pharmacology and Therapeutics.

NIDA NewsScan, May 19, 2006

New research suggests that different levels of sensitivity to drug cues may exist in the brains of smokers. These differences may be influenced by the degree to which smokers crave cigarettes.

Dr. Joseph McClernon and colleagues from the Duke University Medical Center in North Carolina examined brain activity in regions associated with attention, motivation, and reward. All of the 13 adult smokers completed two brain scan sessions (1 following a period of overnight abstinence, and the other following smoking as usual) while viewing a series of pictures, including smoking-related objects and people smoking cigarettes. Study participants provided self-reports of cravings before, during, and after each session.

Although all smokers reported cravings following both sessions, the researchers found that smokers who reported a greater urge to smoke following the period of abstinence also exhibited stronger brain activity after viewing smoking-related images. In contrast, smokers who reported fewer cravings displayed stable or decreased brain activity, despite viewing the same smoking-related images after a period of abstinence.

What it means: These findings suggest that important differences may exist in the brains of smokers. These differences may influence levels of cigarette craving following abstinence and may also affect the impact of smoking cues. Smokers who experience a greater sensitivity to smoking cues may have difficulty quitting smoking and may also be more prone to relapse.

The researchers published these study findings in the May 2005 issue of Neuropsychopharmacology.

NIDA NewsScan, February 1, 2006

Results of a study performed in mice show that naloxone was able to block activation of the brain’s molecular pathways that reinforce smoking behaviors and keep the mice from seeking out more nicotine. Naloxone belongs to a class of compounds known as opiate antagonists, which can prevent certain drugs, such as morphine and heroin, from latching onto receptors in the brain.

The scientists saw that when they gave nicotine to normal mice, activity of a particular protein known to play a role in the rewarding properties of many drugs of abuse increased in various brain regions. They again observed increased activity of this protein when normal mice previously given nicotine were placed in the environment they associated with receiving the drug. But when the scientists treated mice with naloxone before exposing them to the nicotine-associated environment, the activity of this protein was blocked, as was the behavioral response associated with reward.

The researchers suggest that future studies evaluating the efficacy of opiate antagonists or other drugs capable of blocking the activity of this protein would be useful in humans to see if they block the craving in quitters exposed to visual or olfactory stimuli that may rekindle the desire to smoke.

What it means: Environmental cues related to smoking activate some of the same molecular pathways in the brain as direct exposure to nicotine. However, this study shows that medications such as naloxone may help block this action in nicotine addiction, thereby offering promise for smokers who want to quit, and alternatives or additions to current smoking cessation therapies.

Dr. Julie Blendy and her colleagues at the University of Pennsylvania published their findings in the June 16, 2005 issue of the journal Neuron.

NIDA NewsScan, February 1, 2006

Recent research in rats suggests that nicotine mimics the effects of hypocretin, a protein thought to help regulate sleep and wakefulness, in the prefrontal cortex, a part of the brain important in tasks requiring attention.

In the study, 10 adult male rats were trained to pay attention to a visual stimulus, upon which they would poke a target and be rewarded with food. After learning the task, the prefrontal cortices of all 10 rats were successively infused with saline, nicotine, and a low or high dose of hypocretin.

The researchers found that infusions of both nicotine and hypocretin improved the ability of the rats to pay attention and follow through on a task, even when conditions were demanding. Further analyses showed that nicotine and the higher dose of hypocretin improved accuracy in the task under the most demanding condition.

What it means: This is the first study to suggest that hypocretin plays a role in attention, and further demonstrates that hypocretin and nicotine act similarly to enhance attention and performance. An implication is that the cognitive effects of nicotine—normally administered in intermittent bursts through smoking—need to be considered in smoking cessation treatments. The scientists suggest that a constant, low level of nicotine infused into the body from a patch may desensitize rather than activate nicotine receptors.

The study, led by Dr. Evelyn Lambe of Yale University School of Medicine, was published in the May 25, 2005 issue of the Journal of Neuroscience.

NIDA NewsScan, February 1, 2006

Despite declining trends in adolescent smoking, more than 25 percent of 12th-graders report smoking in the past month, and 17 percent report daily smoking. Now, a recent study indicates motivation is not enough by itself to keep teens away from cigarettes.

Dr. Suzanne Colby and colleagues from Brown University recruited 85 non-treatment-seeking adolescent smokers ages 14¨C19 who were randomly assigned to receive either one session of motivational interviewing (MI) or standardized brief advice (BA). At the beginning of the study, the teens were interviewed and completed questionnaires to determine their daily cigarette, marijuana, and alcohol use. Additional assessments were made at 1, 3, and 6 months postintervention. Trained interventionists presented the MI group with the pros and cons of smoking and quitting; and helped patients formulate detailed action plans, anticipate barriers, and develop strategies for overcoming them. Members of the BA group were advised to quit smoking and received a pamphlet on quitting and a list of local treatment referrals.

Overall, abstinence rates were low but consistent with findings from previous adolescent smoking cessation trials. Results showed reduced smoking for both groups at 6 months, but not at 1 month. At 3-month followup, only those in MI showed significant reductions compared to the beginning of the study.

What it means: Although teens who received MI fared better than those who received standardized BA, motivation alone did not sustain smoking cessation. Future research should examine the efficacy of MI paired with skills training and/or additional resources when helping teens quit smoking.

These NIDA-supported findings were published in the June 2005 issue of Addictive Behaviors.

NIDA NewsScan, September 7, 2005

Reductions in state-sponsored anti-tobacco advertisements may provide short-term savings, but increased smoking and smoking-related diseases may result in long-term costs for states.

Using national and state-based data sets, including Nielson media research, state tobacco control policy data, and Monitoring the Future surveys, to compile data for 51,085 students in grades 8, 10, and 12, a team of NIDAfunded researchers from the University of Illinois at Chicago examined the relationship between tobacco-related beliefs, attitudes, and behaviors and exposure to state-sponsored, televised, anti-tobacco advertising.

Researchers found that students living in states with at least one televised, state-sponsored ad held greater anti-smoking attitudes and beliefs and were less likely to smoke than students who were not exposed to anti-tobacco ads. In addition, higher Targeted Rating Points (TRPs)--a national rating system that estimates frequency and reach of advertising to 12- to 17-year-olds--were associated with significantly greater odds of holding antismoking attitudes, beliefs, and behaviors.

What it means: Televised, state-sponsored, anti-tobacco media campaigns positively influence antismoking attitudes, beliefs, and behaviors in U.S. youth, and may be an effective strategy for preventing and reducing smoking in youth.

This study, led by Dr. Sherry Emery of the University of Illinois at Chicago, was published in the July 2005 issue of Archives of Pediatric & Adolescent Medicine.

NIDA NewsScan, September 7, 2005

Research has indicated that women smokers have more difficulty quitting and maintaining abstinence from cigarettes than men. Several factors may contribute to gender differences in smoking cessation outcomes, including depression and fears of gaining weight. NIDA-funded scientists have found that the antidepressant medication bupropion may help women who are light smokers maintain abstinence at rates similar to those of men.

For the study, the researchers recruited 314 women and 241 men who smoked at least 10 cigarettes per day. Participants were assigned to receive bupropion, commonly known as Zyban or Wellbutrin, accompanied by behavioral counseling or counseling only. Behavioral counseling was designed to help participants reduce smoking, learn to cope with stress and situations that trigger their desire to smoke, and prevent relapse. Two weeks after participants began taking bupropion, or on the day of the third counseling session, they were instructed to stop smoking. Abstinence from smoking was evaluated at 8 weeks (end of treatment) and 6 months after the quit date, and was verified by saliva analysis for the presence of cotinine, an indicator of smoking.

At the end of treatment, 51 percent of the men and 40 percent of the women had remained abstinent from smoking. At the 6-month follow-up, about 32 percent of the men and 22 percent of the women were abstinent from smoking.

The researchers found that, overall, women receiving both bupropion and behavioral counseling had abstinence rates similar to those of the men. However, women receiving behavioral counseling alone were more likely to relapse to smoking than the men. At the end of treatment, about 55 percent of the women receiving bupropion were abstinent from smoking compared with 35 percent of those receiving behavioral counseling alone. Women who received bupropion and smoked fewer than 20 cigarettes per day were twice as likely to remain abstinent than those receiving behavioral counseling alone. However, bupropion had little effect on the abstinence rates of women who smoked more than 20 cigarettes per day. For men, however, bupropion was more effective for heavy smokers than light smokers.

What it means: These findings indicate that bupropion may be an effective treatment for women who are light smokers. Identifying gender-specific smoking cessation factors will aid in the development of more effective treatment programs targeted to women.

This study was published in the February 2004 issue of Nicotine and Tobacco Research by lead investigator Bradley Collins at the University of Pennsylvania.

NIDA NewsScan, April 30, 2004

NIDA-funded scientists have developed a new vaccine that successfully reduces the behavioral effects of nicotine in rats. Unlike previously developed vaccines, the new vaccine does not have to be administered with an adjuvant—a substance that enhances the production of antibodies and has been associated with side effects—to be effective.

Nicotine vaccines produce their effects by stimulating the production of antibodies that bind to nicotine and prevent it from reaching the brain. The researchers found that rats vaccinated with the new vaccine had a higher concentration of nicotine-specific antibodies in their blood compared with nonvaccinated rats. When exposed to nicotine, vaccinated rats exhibited a weaker behavioral response.

What it means: These findings indicate the new vaccine is effective in reducing the behavioral effects of nicotine. An appropriately designed nicotine vaccine would be beneficial to those who do not respond to conventional nicotine treatments or who cannot tolerate the side effects associated with current pharmacotherapies.

Dr. Rick A. Bevins at the University of Nebraska-Lincoln and colleagues at the University of Nebraska Medical Center-Omaha published the study in the March 2003 issue of the journal International Immunopharmacology.

NIDA NewsScan, July 30, 2003

Using the 1995-96 and 1998-99 Current Population Survey (CPS) Tobacco Use Supplements, researchers found that smoking prevalence was higher among people born in the United States than among their racial and ethnic counterparts who were foreign-born.

Furthermore, smoking prevalence varied by country of birth for immigrants. For example, smoking prevalence among Asian and Pacific Islander immigrants as a whole was 11.8 percent. Yet when country of origin was considered, smoking prevalence rates ranged from 4.6 percent among Indian immigrants to 21.4 percent among Japanese immigrants.

According to the CPS Tobacco Use Supplements, an estimated 21.6 percent of the American public smokes, but when desegregated by immigrant status, the figures show that native-born respondents had higher smoking rates than foreign born—22.6 percent versus 13.4 percent. Smoking prevalence statistics broken down without regard to immigrant status show that the highest smoking prevalence was reported among American Indians (33.2 percent), followed by Whites, non-Hispanic (22.7 percent), Blacks (20.9 percent), Hispanics (15.5 percent) and Asian and Pacific Islanders (12.7 percent).

What it means: By ignoring immigrant status, smoking prevalence statistics may hide segments within broadly defined racial and ethnic groups that have vastly different smoking behaviors than the aggregated group. Including findings about country of origin and immigrant status can greatly enhance the development of targeted and culturally sensitive smoking cessation programs.

Dr. Kaari Flagstad Baluja, Julie Park and Dr. Dowell Myers conducted the research under the auspices of the Transdisciplinary Tobacco Use Research Center at the University of Southern California. The study was published in the April 2003 issue of the American Journal of Public Health.

NIDA NewsScan, May 23, 2003

Surveys of more than 7,000 individuals questioned periodically from middle school through their mid-30’s about their beliefs concerning the risks from smoking cigarettes and the value they place on health reveal that these attitudes change with age.

A research team from Arizona State University and Indiana University drew participants for the study from a large, Midwestern community. At the most recent assessment, 26 percent smoked cigarettes. The researchers found that:

• Between the ages of 11 and 14, the perception that smoking would harm one’s own health decreased. However, between the ages of 15 and 18 and continuing to age 24, there was an increased belief that smoking can be harmful to one’s personal health.

• Throughout adolescence and young adulthood, there was a small but statistically significant increase in the belief that cigarette smoking is harmful to people’s health in general.

• Between the ages of 15 and 18, the value that adolescents placed on health decreased. However, the value placed on health increased starting at age 19 and continued to increase up to age 29.

• Between ages 11 and 14, belief in the positive

psychological consequences of smoking increased; however this trend reversed between ages 15 and 18.

• Between 11 and 14, the belief that cigarettes are addicting decreased, but between the ages of 15 and 18 and between ages 19 and 24, both smokers and nonsmokers increased their belief that cigarettes are addicting.

• Across all age groups, those who smoked were significantly less likely to believe that smoking is harmful to either health in general or to their own personal health, and smokers placed significantly less value on health than did nonsmokers.

What it means: Smoking interventions aimed at adolescents must counter the perception among middle school students that cigarette smoking does not pose a risk of addiction or a risk to one’s own health, and must counter the declining values placed on health by high school students.

The research team led by Drs. Laurie Chassin and Clark Presson from Arizona State University and Dr. Steven J. Sherman from Indiana University published the study in the September, 2001 issue of Health Psychology.

NIDA NewsScan, January 30, 2002

Researchers at the Brown University School of Medicine have found that smokers with a history of recurrent major depressive disorder (MDD) who received standard treatment for smoking cessation – combined with behavioral coping therapy for depression – were more likely to be successful in quitting than those receiving standardtreatment alone.

Interestingly, heavy smokers also benefited from the inclusion of therapy for depression in their stop-smoking treatment regimen, regardless of their history of depression.The researchers recruited 179 smokers, more than half of whom were women, between the ages of 18 and 70. All had a history of MDD; some had experienced a single episode, while others had experienced recurrent bouts of depression.

Participants were currently smoking an average of 27 cigarettes per day and on average had been smokers for more than 27 years.

A year after a 6-week treatment program, 24.7 percent of the standard therapy group – compared to 32.5 percent of the combination therapy group – had stopped smoking. The study found that individuals with a history of recurrent episodes of depression had poorer treatment outcomes than did those with only a single episode of depression.

What it means: This study indicates that incorporating treatment for depression into standard smoking cessation therapy may be beneficial for smokers with a history of recurrent MDD and for those who smoke heavily.

The study, led by Dr. Richard Brown of the Brown University School of Medicine, appears in the May 2001 issue of Journal of Clinical and Consulting Psychology.

NIDA NewsScan, October 16, 2001

To better understand the brain mechanisms through which nicotine influences thinking, motor skills, and behavior, researchers in NIDA's Brain Imaging Center in Baltimore, Maryland used positron-emissiontomography (PET) assays to measure changes in cerebral blood flow during a memory test.

A total of 11 smokers and 11 ex-smokers completed the study. Smokers were asked to abstain from cigarettes for 12 hours prior to the memory test. Each subject participated in two PET assays. In one PET session, subjects received nicotine gum; in the other, they received a placebo gum. The subjects were asked to remember the sequence of a series of three letters that were being changed constantly. The percentage of correct and incorrect responses, reaction times, and reaction time variability were analyzed. Abstinent smokers, but not ex-smokers, showed significantly improved performance on the memory test after being given nicotine gum, compared with their performance after taking placebo gum. Thedecreased blood flow in certain regions of the smokers' brains compared with increased cerebral blood flow in ex-smokers after

chewing nicotine gum is the first evidence of tolerance to nicotine measured directly in the human brain. The PET assays showed that in ex-smokers given the placebo gum, the percentage of correct responses was correlated with increased blood flow in the left hemisphere of the brain. For smokers given the placebo gum, the percentage of correct responses was correlated with increased blood flow in the right hemisphere.

What it means: The differences in cerebral blood flow were seen as a function of nicotine addiction, suggesting that chronic exposure to nicotine or withdrawal from nicotine affects cognitive strategiesused to perform memory tasks. The lack of increased blood flow after nicotine administration in smokers likely reflects tolerance.

The paper was published by lead investigator Dr. Monique Ernst in the April 10, 2001 issue of the Proceedings of the National Academy of Sciences and is available online at www.pnas.org.

NIDA NewsScan, July 24, 2001