Erotic Stimulus Processing under Amisulpride and Reboxetine: A Placebo-Controlled fMRI Study in Healthy Subjects

Abstract

Background:Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects.Methods:Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire.Results:Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged.Conclusions:In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents.

Local and Global Resting State Activity in the Noradrenergic and Dopaminergic Pathway Modulated by Reboxetine and Amisulpride in Healthy Subjects

“…Resting state fMRI data were acquired as part of the protocol, including a separate functional task–related MRI experiment and resting state perfusion data, which are reported elsewhere ( Viviani et al, 2013 ; Graf et al, 2015 ).…”

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.…”

Differential Noradrenergic Modulation of Monetary Reward and Visual Erotic Stimulus Processing

“…The Massachusetts General Hospital Sexual Functioning Questionnaire [MGH-SFQ; ( 23 )] was administered to evaluate baseline sexual interest, sexual arousal, the ability to achieve orgasm, ability to achieve and maintain an erection, and overall sexual satisfaction prior to the study. According to the study protocol, the questionnaire was modified to assess changes in subjective sexual functioning only over the past week of medication ( 9 , 13 ). The study was approved by the local ethical committee of Ulm University and all participants gave written informed consent according to the Declaration of Helsinki.…”

“…We used an established monetary reward paradigm ( 6 ) with a parametric variation of probabilities (0, 25, 50, 75, and 100%) to win 1 Euro (€) (see Figure 1 ). Taking into account that this investigation was conducted within a broader study design ( 13 , 14 ), the monetary reward paradigm had to be shortened to reduce total scanner time. In contrast to 120 trials applied in previous studies conducted with the same task ( 6 , 27 , 28 ), each subject completed 60 trials (6,250 ms each), 12 per each probability in a randomized order.…”

“…To complement our findings on serotonergic and dopaminergic/noradrenergic agents, we further investigated neural correlates of primary rewards by 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 ). Here, subjective sexual behavior along with corresponding neural activations were not altered by amisulpride compared to placebo, presumably due to its prodopaminergic properties under low dosages (200 mg/d) ( 15 , 16 ) as used in this study.…”