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

Abstract

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.

Differential Noradrenergic Modulation of Monetary Reward and Visual Erotic Stimulus Processing

“…Though, in this study, attenuated neural activations under REB were also found within the medial orbitofrontal cortex, previously related to the coding of pleasantness or received reward ( 37 ). Evidence supporting the interpretation of a differential modulation of primary erotic and secondary monetary rewards within the Nacc ( 11 ) highly similar to the current study was also found in our previous study with the SSRI paroxetine. The similarity of the findings under the noradrenergic agent REB as found in this study may be plausible considering some anatomical overlap of these two neuromodulatory pathways ( 21 ).…”

“…Thus, we now examined neural correlates of secondary reward and prediction error processing under reboxetine and amisulpride compared to placebo within the same healthy study sample in which we recently investigated the hedonic aspects of primary rewards by visual erotic picture stimulation ( 14 ). Paralleling our previous investigations on serotonergic agents ( 11 ), we focused on the Nacc as core region of the mesolimbic dopaminergic system ( 4 , 5 ) and expected unimpaired neural prediction error signals under the noradrenergic antidepressant reboxetine. The hypothesis was guided by findings of some anatomical overlap of the serotonergic and noradrenergic system ( 21 ) and the clinical observation that successful outcomes in environments requiring learning and adaptation of behavior such as behavioral psychotherapy, are even facilitated by antidepressants ( 22 ).…”

“…Specifically, neural activations within the Nacc were diminished under the serotonergic agent ( 9 ), potentially due to increased reciprocal interactions with the orbitofrontal cortex ( 10 ). Investigations in the same sample of healthy subjects under these two agents, bupropion and paroxetine ( 11 ), however, revealed that the serotonergic dampening of the neural reward system is potentially restricted to primary reinforcers, i.e., rewards with an intrinsic, not learned reward value such as visual erotic stimuli ( 12 ), and was not evident in a monetary incentive task. For the secondary rewards, signals related to prediction error processing were even more pronounced.…”

Dopamine Transporter and Reward Anticipation in a Dimensional Perspective: A Multimodal Brain Imaging Study

“…Regarding reward processing, whether SSRI treatment influences functional activity during reward tasks in patients with depression remains unclear. In healthy controls, SSRI treatment was shown to reduce the responsiveness to reward in fMRI (Macoveanu et al, 2014;Graf et al, 2016). However, Stoy et al (2012) evidenced a hyporeactivity to reward in unmedicated depressed patients, which is normalized after successful SSRI treatment.…”

Belohnung und das Opioidsystem

“…Darüber hinaus wird das dopaminerge Belohnungssystem durch weitere Neuromodulatoren beeinflusst. So konnten wir in unserer Abteilung die Beeinflussung des dopaminergen Belohnungssystems durch das Serotonin-und Noradrenalinsystem mittels funktioneller Magnetresonanztomografie (fMRT) bildgebend darstellen (12)(13)(14)(15)(16)(17). In diesem Artikel sollen grundlegende Mechanismen und klinische Aspekte zur Beeinflussung des dopaminergen Belohnungssystems durch das Opioidsystem vorgestellt werden.…”