Genetic modulation of nicotine effects on emotional on reward processing
Final Report Abstract
Nicotine acts on the mesocorticolimbic system and affects motivational processes, which might be critical for tobacco use and the risk to relapse. The overarching goal of the project was to improve our understanding of acute and chronic effects of nicotine and smoking on essential aspects of motivated behavior and the neural correlates subserving the processing of reward. Using functional magnetic resonance imaging (fMRI), we investigated acute effects of nicotine as well as changes due mid-term nicotine abstinence after smokers underwent a cessation program. In the 1st funding period we showed that during anticipation of monetary rewards dependent compared to occasional smokers showed less motivation to work for monetary reward and a blunted activation in the ventral striatum which is a key structure of the brain reward system. In the 2nd funding period, we could replicate this differences, and additionally showed that occasional smoker’s reactivity to reward is higher than in non-smokers, which in turn did not differ from the dependent smokers. Moreover, mid-term abstinence of 2-5 weeks did not significantly change reward reactivity in smokers. Interestingly, smokers with increased risk for relapse showed attenuated tracking of reward values in nucleus accumbens, ventromedial prefrontal cortex, and the lateral orbitofrontal cortex in the first session before cessation and were less capable to optimize their task behavior during the second session after midterm abstinence. Effects of acute nicotine on reward anticipation and task behavior were generally modest. The most pronounced effect of nicotine was that it generally increased motor response speed. Regarding inter-temporal decision-making, we showed that smokers discounted delayed rewards to a greater extent than non-smokers (i.e. they more often preferred earlier and smaller rewards over later and larger rewards). They additionally showed reduced activation in parietal and occipital brain regions during inter-temporal choices. Interestingly, discounting behavior in smokers undergoing a smoking cessation program did neither differ from the controls, nor was it significantly affected by abstinence. However, both intra- and inter-individual variability of intertemporal choices were associated with a higher risk for relapse. Contrary to our hypotheses, nicotine did not significantly affect discounting behavior. Our data thus indicate that differences in behavioral and neural responses to delayed rewards between smokers and non-smokers are not primarily due to nicotine. We hypothesize that these differences are preexisting and might contribute to liability for tobacco dependence and relapse. Regarding decision-making under risk, we found that nicotine did neither affect behavior nor brain activation. On the one hand, smokers compared to non-smokers showed a stronger tendency to avoid gambles when they were advantageous, but they gambled more often when they were disadvantageous. Furthermore, smokers displayed a stronger preference for negatively skewed gambles that incur a small chance of a very bad outcome. Both distortions in decision-making would lead to a lower return in the long run. Taken together the effects of acute nicotine as well as those of mid-term nicotine abstinence on reward related behavior and brain activity were less pronounced than expected. Differences between dependent smokers, occasional smokers and non-smokers reported by others or observed by us seem to arise after chronic nicotine use and then to be stable over at least 2 to 5 weeks of abstinence. Alternatively, these group differences might be mostly preexistent and presumably predispose subjects to develop and maintain nicotine addiction. Thereby, such trait markers might be targeted by future interventions to prevent or treat tobacco dependence.
Publications
- (2013) Fasting levels of ghrelin covary with the brain response to food pictures. Addict Biol, 18(5), 855-62
Kroemer, N.B., Krebs, L., Kobiella, A., Grimm, O., Pilhatsch, M., Bidlingmaier, M., Zimmermann, U.S. & Smolka, M.N.
(See online at https://doi.org/10.1111/j.1369-1600.2012.00489.x) - (2013) Nicotine alters food-cue reactivity via networks extending from the hypothalamus. Neuropsychopharmacology, 38(11), 2307-14
Kroemer, N.B., Guevara, A., Vollstädt-Klein, S. & Smolka, M.N.
(See online at https://doi.org/10.1038/npp.2013.133) - (2013). Altered reward processing in adolescents with prenatal exposure to maternal cigarette smoking. JAMA Psychiatry, 70(8), 847-856
Müller, K.U., Mennigen, E., Ripke, S., … Smolka, M.N.
(See online at https://doi.org/10.1001/jamapsychiatry.2013.44) - (2014) Acute and chronic nicotine effects on behaviour and brain activation during intertemporal decision making. Addict Biol, 19(5), 918-30
Kobiella, A., Ripke, S., Kroemer, N.B., Vollmert, C., Vollstädt-Klein, S., Ulshöfer, D.E. & Smolka, M.N.
(See online at https://doi.org/10.1111/adb.12057) - (2014) Balancing reward and work: Anticipatory brain activation in NAcc and VTA predict effort differentially. Neuroimage, 102 Pt 2, 510-9
Kroemer, N.B., Guevara, A., Ciocanea Teodorescu, I., Wuttig, F., Kobiella, A. & Smolka, M.N.
(See online at https://doi.org/10.1016/j.neuroimage.2014.07.060) - (2015) Nicotine enhances modulation of food-cue reactivity by leptin and ghrelin in the ventromedial prefrontal cortex. Addict Biol, 20(4), 832-44
Kroemer, N.B., Wuttig, F., Bidlingmaier, M., Zimmermann, U.S. & Smolka, M.N.
(See online at https://doi.org/10.1111/adb.12167)
