abuse is hedonic dysregulation—the feeling that there is little pleasure in life. Activities that were once rewarding are no longer enjoyable (Koob and Le Moal, 1997). It is hypothesized that a relative deficiency in dopamine release after long-standing nicotine exposure accounts for many of the mood disorders and for the tobacco craving that may persist for long periods after quitting (Benowitz, 2009).

Conditioned Behavior and Nicotine Addiction

All drug-taking behavior is learned—a result of conditioning. It is reinforced by the consequences of the pharmacologic actions of the drug in question, as discussed above in relation to nicotine. At the same time, the user begins to associate specific moods, situations, or environmental factors with the rewarding effects of the drug. Respiratory-tract sensory cues associated with tobacco smoking are a type of conditioned reinforcer that has been shown to play an important role in the regulation of smoke intake, the craving to smoke, and the rewarding effects of smoking (Rose et al., 1993, 2000). The association between such cues and expected drug effects and the resulting urge to use the drug is a type of conditioning. Animal studies have found that repeated nicotine exposure increases the behavioral control of conditioned reinforcers (such as tobacco cues) contributing to the compulsivity of smoking behavior (Olausson et al., 2004).

Cigarette smoking is maintained, in part, by such conditioning. People habitually smoke cigarettes in specific situations, such as after a meal, with coffee or alcoholic beverages, or in the presence of other smokers. The repeated association between smoking and particular events causes specific environmental situations to become powerful smoking cues. Likewise, aspects of the drug-taking process, such as the manipulation of smoking materials, the taste or smell of smoke, or the feeling of it in the throat, become associated with the pleasurable effects of smoking. Even unpleasant moods can become conditioned cues for smoking. For example, a smoker may learn that not having a cigarette provokes irritability (a common symptom of the nicotine-abstinence syndrome) whereas smoking a cigarette provides relief. After such repeated experiences, a smoker may come to regard irritability from any source, such as stress or frustration, as an indicator to smoke (Benowitz, 2009).

Genetics of Nicotine Addiction

Twin studies have indicated a high degree of heritability (at least 50%) in the prevalence of cigarette-smoking, the ability to quit smoking, the number of cigarettes smoked per day (Lessov-Schlaggar et al., 2008),

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