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Abstract

Introduction:
We recently investigated the effects of the noradrenergic antidepressant reboxetine (REB) and the antipsychotic amisulpride (AMS) compared to placebo (PLA) on neural correlates of primary reinforcers by visual erotic stimulation in healthy subjects (Graf et al. 2017). Whereas AMS left subjective sexual function and corresponding neural activations unimpaired, attenuated neural activations were observed within the nucleus accumbens (Nacc) along with diminished behavioural sexual functioning under REB. However, a global dampening of the reward system under REB seems not intuitive considering the complementary role of the noradrenergic to the dopamine system in reinforced learning as coded in prediction error processing.
Methods:
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 prediction error signalling. Participants took REB (4mg/d), AMS (200mg/d) and PLA 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 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.
Results:
We could confirm our previous results from the whole brain analysis for the selected ROI by significant (p<0.05 FWE-corrected) attenuated Nacc-activations during visual sexual stimulation under REB compared to PLA. However, neural activations concerning prediction error processing and monetary reward expectation were unimpaired or even increased under REB compared to PLA along with unimpaired reaction times in the reward task. For both tasks, neural activations and behavioural processing were not altered by AMS compared to PLA.
Conclusions:
With attenuated neural activations within the Nacc during visual erotic stimulation and otherwise unimpaired or even increased neural prediction error and monetary reward expectancy processing, our results provide evidence regarding a differential modulation of the neural reward system by the noradrenergic agent REB according to the presence of primary reinforcers such as erotic stimuli in contrast to secondary such as monetary rewards.