Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Endocrine signals such as ghrelin and leptin are known to modulate the mesocorticolimbic dopaminergic system and, consequently, show associations with food and drug reward. In animal models, nicotine was demonstrated to reduce body weight by attenuating food intake and effects of leptin and ghrelin are partly modulated by nicotinic acetylcholine receptors which hint at potential interactions. However, the neuropharmacological modulation of endocrine signals by nicotine in healthy humans remains to be tested experimentally. We used functional magnetic resonance imaging to investigate food‐cue reactivity after an overnight fast and following a caloric load (oral glucose tolerance test, <jats:styled-content style="fixed-case">OGTT</jats:styled-content>) in 26 healthy normal‐weight never‐smokers. Moreover, we administered either nicotine (2 mg) or placebo gums using a randomized cross‐over design and assessed blood plasma levels of ghrelin and leptin. During fasting, nicotine administration decreased correlations with ghrelin levels in the mesocorticolimbic system whereas correlations with leptin were increased. After the <jats:styled-content style="fixed-case">OGTT</jats:styled-content>, nicotine increased the modulatory effects of ghrelin and leptin on food‐cue reactivity, particularly in the ventromedial prefrontal cortex (<jats:styled-content style="fixed-case">vmPFC</jats:styled-content>) and the amygdala. Critically, this led to an indirect modulation of the behavioral ‘appetizer effect’ (i.e. cue‐induced increases in subjective appetite) by homeostatic feedback signals via food‐cue reactivity in <jats:styled-content style="fixed-case">vmPFC</jats:styled-content>. We conclude that nicotine enhances the effect of ghrelin and leptin in the valuation and relevance network which might, in turn, reduce appetite. This highlights that amplifying the impact of homeostatic signals such as ghrelin and leptin in normal‐weight individuals might hint at a mechanism contributing to nicotine's anorexic potential.</jats:p>