Abstract
We recently investigated the effects of the noradrenergic antidepressant reboxetine and the antipsychotic amisulpride compared to placebo on neural correlates of primary reinforcers by visual erotic stimulation in healthy subjects. Whereas, amisulpride left subjective sexual functions and corresponding neural activations unimpaired, attenuated neural activations were observed under reboxetine within the nucleus accumbens (Nacc) along with diminished behavioral sexual functioning. However, a global dampening of the reward system under reboxetine seemed not intuitive considering the complementary role of the noradrenergic to the dopamine system in reward-related learning mediated by prediction error processing. We therefore investigated the sample of 17 healthy males in a mean age of 23.8 years again by functional magnetic resonance imaging (fMRI), to explore the noradrenergic effects on neural reward prediction error signaling. Participants took reboxetine (4 mg/d), amisulpride (200 mg/d), and placebo each for 7 days within a randomized, double-blind, within-subject cross-over design. During fMRI, we used an established monetary incentive task to assess neural reward expectation and prediction error signals within the bilateral Nacc using an independent anatomical mask for a region of interest (ROI) analysis. Activations within the same ROI were also assessed for the erotic picture paradigm. We confirmed our previous results from the whole brain analysis for the selected ROI by significant (p < 0.05 FWE-corrected) attenuated activations within the Nacc during visual sexual stimulation under reboxetine compared to placebo. However, activations in the Nacc concerning prediction error processing and monetary reward expectation were unimpaired under reboxetine compared to placebo, along with unimpaired reaction times in the reward task. For both tasks, neural activations and behavioral processing were not altered by amisulpride compared to placebo. The observed attenuated neural activations within the Nacc during visual erotic stimulation along with unimpaired neural prediction error and monetary reward expectation processing provide evidence for a differential modulation of the neural reward system by the noradrenergic agent reboxetine depending on the presence of primary reinforcers such as erotic stimuli in contrast to secondary such as monetary rewards.
Highlights
The prospect of rewards is fundamental for human motivation, goal-directed behavior and learning [1]
We previously investigated the neural correlates of primary reinforcers by functional magnetic imaging and visual erotic video clip stimulation under the selective serotoninreuptake inhibitor (SSRI) paroxetine and the selective dopamine and noradrenaline reuptake inhibitor (SDNRI) bupropion compared to placebo in healthy subjects [9]
To complement our findings on serotonergic and dopaminergic/noradrenergic agents, we further investigated neural correlates of primary rewards by functional magnetic resonance imaging (fMRI) and visual erotic stimulation under the antipsychotic amisulpride and the selective noradrenaline reuptake inhibitor (SNRI) reboxetine compared to placebo in healthy subjects [13, 14]
Summary
The prospect of rewards is fundamental for human motivation, goal-directed behavior and learning [1]. Considering the reinforcement learning model [3], learning about reward-predictive cues, and the acquisition of secondary rewards, is regulated by prediction error coding. Receipts of unpredicted rewards are related to increased neural activations and phasic dopaminergic responses within the Nacc and led to behavioral learning with the occurrence of reward [4]. The omission of predicted rewards is accompanied by an attenuated neural signaling [6] and extinction of the corresponding behavior with the loss of incentive value. Whereas the pivotal role of the neuromodulator dopamine (DA) has been extensively investigated regarding reinforcement learning and prediction error processing [5, 7, 8], evidence regarding the modulation of the Nacc-activations by other neurotransmitters and under presence of various reinforces is scarce
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