Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli Nicole Y.L. Oei a,b,c, * , Stephanie Both c,d , Diana van Heemst a,e , Jeroen van der Grond b a Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands b Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands c Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands d Department of Gynaecology, Leiden University Medical Center, Leiden, The Netherlands e Netherlands Consortium of Healthy Ageing, The Netherlands Received 14 May 2013; received in revised form 8 October 2013; accepted 8 October 2013 Psychoneuroendocrinology (2014) 39, 111—120 KEYWORDS Cortisol; Social stress; Backward masking; Functional Imaging; Nucleus Accumbens; Reward Summary Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain’s ‘‘reward system’’, and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PET studies indicate that the stress hormone cortisol may be crucial in the interaction between stress and dopaminergic actions. In the present study we therefore investigated whether cortisol mediated the effect of stress on DA-related responses to -sublimi- nal-presentation of reward cues using the Trier Social Stress Test (TSST), which is known to reliably enhance cortisol levels. Young healthy males (n = 37) were randomly assigned to the TSST or control condition. After stress induction, brain activation was assessed using fMRI during a backward-masking paradigm in which potentially rewarding (sexual), emotionally negative and neutral stimuli were presented subliminally, masked by pictures of inanimate objects. A region of interest analysis showed that stress decreased activation in the NAcc in response to masked sexual cues (voxel-corrected, p < 05). Furthermore, with mediation analysis it was found that high cortisol levels were related to stronger NAcc activation, showing that cortisol acted as a suppressor variable in the negative relation between stress and NAcc activation. The present findings indicate that cortisol is crucially involved in the relation between stress and the responsiveness of the reward system. Although generally stress decreases activation in * Corresponding author at: Leiden Institute for Brain and Cognition (LIBC), Postzone C2-S, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Tel.: +31 71 526 4972; fax: +31 71 524 8256. E-mail address: noei@xs4all.nl (N.Y.L. Oei). Available online at www.sciencedirect.com ScienceDirect j our na l h omepa g e: www.e lse vie r.c om/l oca te/ psyne ue n 0306-4530/$ — see front matter # 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psyneuen.2013.10.005