## INTRODUCTION

In the United States approximately 443,000 deaths in 2007 were attributable to cigarette smoking, according to the Centers for Disease Control and Prevention (CDC). This number makes cigarette smoking the principal cause of premature death and disability in the country.1 In addition, the average annual smoking-attributable health care expenditures nationwide were approximately $96 billion during 2001–2004. Then when combined with productivity losses of$97 billion, the total economic burden of smoking was approximately \$193 billion per year.2 Furthermore, the International Agency for Research on Cancer has reported that tobacco smoking is causally linked to 13 types of neoplastic disease.3 Unfortunately, despite tobacco control efforts, including public education about the health hazards of smoking, many smokers continue to encounter extreme difficulty quitting and maintaining long-term abstinence from tobacco.

According to the 2007 National Health Interview Survey, one fifth of the US population consisted of current smokers, smoking rates were substantially higher among those with less than a high school education than those with more education, and 40% of the current smokers had made at least one quit attempt of at least 24 hours in the previous year.1 According to the National Survey on Drug Use and Health performed that same year, nearly 42% of adults 18 to 25 years old reported using cigarettes in the previous month, whereas only 8% reported using an illicit drug and 7% were classified as heavy alcohol users.4 Finally, in the most recent Monitoring the Future (MTF) survey conducted in 2009, 20%, 33%, and 43% of 8th-, 10th-, and 12th-grade students, respectively, reported that they had smoked cigarettes in their lifetime, as well as 9%, 15%, and 16%, respectively, reported they have used smokeless tobacco in their lifetime.5

Although most smokers (~70%) report an interest in quitting, if not receiving assistance in smoking cessation, fewer than 6% are abstinent at 1 month after their quit date and fewer than 2% are abstinent at 1 year.6 Difficulty in maintaining abstinence is strongly related to affective and cognitive dysfunction, which may persist for some time after the initial cessation in addition to postcessation cigarette cravings.7

The health consequences associated with smoking tobacco are substantial and life-threatening. Smoking is the primary causal factor for 30% of deaths due to cancer and 80% of deaths related to chronic obstructive pulmonary disease.8 The three leading causes of smoking-attributable deaths are lung cancer, ischemic heart disease, and chronic obstructive pulmonary disease. In the last half century the number of smoking-related deaths has remained relatively unchanged even though cigarette use has declined substantially.2

## BIOLOGICAL, BEHAVIORAL, AND COGNITIVE ASPECTS OF NICOTINE DEPENDENCE

### The Reward Pathway

Like most drugs associated with abuse and dependence, nicotine stimulates a rapid increase in dopamine release in the nucleus accumbens and the ventral tegmental area. The stimulation typically occurs within 10 ...

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