Mechanisms of Nicotine Addiction
In developed countries, it is estimated that tobacco use is the leading single cause of premature death (63). The irony of this statistic is that in developed countries, we are constantly being badgered about the dangers of tobacco use. In the end, the rewarding characteristics that tobacco and nicotine exert upon our neurochemistry are enough to overpower any voice of reason. So what's going on here?
Enhancement of dopaminergic activity is considered the universal trademark shared by addictive drugs. When dopamine transmission is impaired, animals will no longer self-administer addictive drugs, including nicotine (64). As we've already discussed, nicotine not only causes dopamine release but also increases the concentration of various dopamine receptors and induces glutamate release, sensitizing the dopaminergic response overtime. Add functional upregulation to the mix, and not only is the dopaminergic response to nicotine robust, it only gets better with continued use.
Putting dopamine aside for a minute, often overlooked is the role of serotonin in drug addiction. Serotonin is intimately involved with our ability to feel satiated as well as control impulsive behavior. Depletion of serotonin levels causes an increase in impulsive behavior as well as a tendency to prefer small immediate rewards to larger delayed rewards (65). It is hypothesized that nicotine may cause a shift in the "balance of power" by increasing dopamine function while simultaneously decreasing serotonin function (66). This hypothesis is supported by the observation that in the frontocortio and limbic areas of the brain, chronic nicotine exposure causes increased dopamine and reduced serotonin levels (67).
Related to impulsive behavior are nicotine's effects on the GABA system, which could theoretically lead to behavioral disinhibition, similar to alcohol. In context, "behavioral disinhibition" means that even when we know we shouldn't smoke, we reach for the cigarette anyway. The bottom line is that nicotine is so addictive not only because it effectively activates the reward centers of our brain (dopamine), it also partially impairs our decision-making ability through its actions on 5-HT and GABA.
Because the dynamics of nicotine addiction span across more than one receptor system, treatment for nicotine addiction should be just as complex. Despite the fact that SSRI's by themselves do little to aid in smoking cessation (80), there is some evidence that they might be of benefit when used in conjunction with transdermal nicotine (81). Thus, a complete "shotgun approach" to quitting nicotine (in whatever form) would include the use of proven effective dopaminergics such as bupropion and/or deprenyl (82,83) along with an SSRI.