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Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected

Graf, Heikoa; Metzger, Coraline D.b,c; Walter, Martinb,d; Abler, Birgita

doi: 10.1097/WNR.0000000000000487

Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy.

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aDepartment of Psychiatry and Psychotherapy III, Ulm University, Ulm

bDepartment of Psychiatry, Otto von Guericke University Magdeburg

cGerman Center for Neurodegenerative Diseases (DZNE)

dLeibniz Institute for Neurobiology, Magdeburg, Germany

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Correspondence to Heiko Graf, MD, Department of Psychiatry and Psychotherapy III, University of Ulm, Leimgrubenweg 12-14, 89075 Ulm, Germany Tel: +49 0 731 500 61553; fax: +49 0 731 500 61402; e-mail:

Received September 13, 2015

Accepted October 6, 2015

© 2016 Wolters Kluwer Health | Lippincott Williams & Wilkins