Psychophysiological and fMRI investigations of tobacco cue reactivity.

Abstract

Development of new smoking-cessation therapies may be facilitated by identifying the neural basis of smoking-related emotional responses. In this dissertation, the affective consequences of cigarette smoking and abstinence were modeled in rats and humans using a potentiated-startle paradigm. In rats, repeated daily nicotine injections resulted in increased startle amplitude 2 h after nicotine exposure, which is consistent with the emergence of an anxiety-like withdrawal episode. In humans, startle responses to tobacco, pleasant, neutral, and unpleasant cues were measured in nonsmokers, nonabstinent smokers, and smokers who were 24 h into a 48 h abstinence period. Startle amplitude was potentiated during unpleasant cues in nonsmokers and abstinent smokers, but not in nonabstinent smokers, which suggests that smoking a cigarette reduced anxiety. Event-related brain potentials also suggested that abstinent smokers were more emotionally reactive than nonsmokers and nonabstinent smokers to both tobacco cues and unpleasant cues. An additional, functional magnetic resonance imaging study found that that two brain regions, the dorsal striatum and the anterior cingulate cortex, were involved in the expression of abstinent smokers' emotional responses to tobacco and unpleasant cues. These results suggest negative affect may be important in maintaining cigarette smoking and that the potentiated startle paradigm is an ideal model for preclinical and clinical studies of smoking-related emotional responses.