Altered amygdala function in nicotine addiction: insights from human neuroimaging studies

More than 5 million deaths a year are attributable to tobacco smoking, making it the largest single cause of preventable death worldwide. The primary addictive component in tobacco is nicotine. Its addictive power is exemplified by the fact that by far most attempts to quit smoking fail. It is therefore mandatory to understand the biological mechanisms by which nicotine leads to continued smoking despite its harmful consequences. While current research perspectives on nicotine addiction emphasize the contribution of reward-related mesocorticolimbic dopamine (DA) systems, the role of the amygdala remains less well characterized, although it is crucially engaged in the emotional and motivational modulation of cognition and behavior. Consequently, we here review brain imaging studies reporting altered neural responses of the amygdala in nicotine addiction. A major focus is placed upon resting-state and cue-induction studies documenting that nicotine addiction is associated with aberrant amygdala activity. Importantly, unprovoked abstinence-induced nicotine cravings have been shown to interfere with the amygdala's ability to detect and adequately respond to harm signals. In light of this empirical evidence, we propose that impaired amygdala-guided harm avoidance and executive functions may be instrumental in maintaining nicotine addiction despite serious health consequences.