Acute and chronic nicotine effects on behaviour and brain activation during intertemporal decision making.

Previous studies demonstrated higher discount rates for delayed rewards in smokers than non-smokers. We performed this study to determine whether those differences in intertemporal choice are due to pharmacological effects of nicotine and to track related brain regions. Thirty-three non-smokers and 27 nicotine-dependent smokers underwent functional magnetic resonance imaging while performing an intertemporal choice task consisting of 40 sets of monetary reward options that varied by delay to delivery. Smokers were investigated in a state of nicotine satiation. Non-smokers were investigated twice, receiving nicotine (2 mg) and placebo gums in a double-blinded, randomized cross-over design. Smokers displayed steeper temporal discounting than non-smokers. Those behavioural differences were reflected in the brain response during the decision between two alternative money/time pairs: smokers showed less activation in parietal and occipital areas (e.g. precuneus) than non-smokers under placebo. A single dose of nicotine in non-smokers led to a similar effect on brain activation but did not impact behaviour. Processing of the reward magnitude of money/time pairs differed between smokers and non-smokers: smokers showed decreased reactivity of the ventral striatum. Moreover, there was an acute nicotine effect in non-smokers on processing of the reward magnitude: nicotine increased the correlation of blood oxygen level-dependent response and mean amount in the left hippocampus, amygdala and anterior insula. We conclude that cross-sectional differences between smokers and non-smokers are only, in part, due to the acute pharmacological effects of nicotine. Longitudinal studies are needed to investigate pre-drug group characteristics as well as consequences of smoking on discounting behaviour and its neural correlates.

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.