Nicotine increases neural response to unpleasant stimuli and anxiety in non-smokers.

Studies in smokers suggest that nicotine might exert anxiolytic, stress-dampening and mood-enhancing effects and beneficially influences neural processing of affective information. Regarding non-smokers, results are inconsistent, and no data exist on the effect of nicotine on neural emotion processing. We applied functional magnetic resonance imaging (fMRI) to assess the influence of nicotine on brain activation during processing of emotional stimuli in 31 non-smokers with a maximum lifetime cigarette consumption of 20 cigarettes. Participants were subjected to two fMRI scans with event-related presentations of images taken from the International Affective Picture System, receiving nicotine (2 mg) and placebo gums in a double-blinded, randomized cross-over design. Furthermore, subjective affect was assessed. Nicotine increased brain activity in response to unpleasant stimuli in the amygdala, anterior cingulate cortex (ACC) and basal ganglia, whereas processing of pleasant stimuli was not altered. Psychophysiological interaction (PPI) analyses revealed that nicotine increased connectivity between the amygdala and the perigenual ACC (pACC) during processing of unpleasant stimuli and decreased connectivity between those structures during processing of pleasant stimuli. Participants reported higher state anxiety under nicotine than placebo. A single dose of nicotine acted as a stressor in non-smokers, leading to increased anxiety and neural activation elicited by unpleasant stimuli as well as altered connectivity within the amygdala-pACC circuit. Besides the possibility that reactions to nicotine may differ between non-smokers and smokers due to tolerance and neuroadaptive processes that occur during prolonged nicotine use, a priori differences in smokers and non-smokers might potentially explain diverse effects of nicotine on affect and emotional reactivity.