example, each puff of a cigarette delivers a bolus dose of nicotine, resulting in a rapid peak, which then falls to a trough level. The time between these bolus doses allows for resensitization of brain nAchRs, so that each delivery can remain reinforcing (Benowitz, 1999). In addition, this route of administration allows the delivery of a greater number or frequency of reinforcements. Other delivery routes result in a slow and persistent absorption of nicotine. Subjective effects, the desire to use more of a drug, and the actual self-administration of a drug are functions of absorption rate (Henningfield and Keenan, 1993). Therefore, whereas cigarettes have high abuse potential, nicotine patches have lower abuse potential.
It is also important to note that addiction to nicotine is not just a biological phenomenon, but also one in which learning or conditioning has taken place. Nicotine self-administration comes under the control of stimuli that have been associated with smoking or tobacco use. These stimuli can precipitate a strong desire for nicotine, withdrawal symptoms, or drug effects. Exposure to these stimuli may lead to the same biological effect on neural substrates as observed from the direct actions of the drug (Childress et al., 1999). Furthermore, stimuli associated with tobacco use, such as the sensory aspects of smoking, can become reinforcing as well; that is, they become secondary reinforcers. In addition a tobacco user develops expectancies regarding the use and effects of the substance, leading to a psychological reliance on the drug.
The susceptibility to nicotine addiction is thus a result of both the biological effects of the drug and learning history. In addition, environmental factors (e.g., access to tobacco, restrictions on tobacco, social modeling) and genetic or organismic factors (e.g., rate of nicotine metabolism, psychiatric disorders, personality factors) may play a significant role. Specific populations might be more vulnerable to nicotine addiction. Genetic twin studies have shown heritability estimates that range from 28 to 84%, with a mean estimate of 53% (Hughes, 1986). Genetic heritability has been associated with the onset as well as the persistence of smoking (Heath et al., 1998, 1999). Examples of what is inherited may be differences in sensitivity to nicotine (Pomerleau, 1995), the rate of nicotine metabolism (Tyndale et al., 1999), or other mechanisms such as genetic polymorphisms in the dopamine transporter and subtypes of dopamine receptors (Lerman et al., 1999; Shields et al., 1998). In addition, individuals with comorbid disorders tend to have a high prevalence of smoking. For example, high prevalence of smoking is found in individuals with depressive disorders, schizophrenia, and alcohol or drug abuse disorders (Breslau, 1995; Hughes et al., 1986a). The mechanisms responsible for susceptibility to smoking may differ across disorders. The nicotine-associated release of neurotransmitters is similar to those found with antidepressants and may be responsible for the association between smoking and depression and