Noradrenergic modulation of neural erotic stimulus perception
Introduction
The investigation of human sexual activity and its modulation by central neurotransmission has been emphasized in recent years due to the increasing evidence of sexual dysfunction under psychopharmacological treatment, e.g. with selective serotonin reuptake inhibitors (SSRIs). Early insights into neuromodulatory effects of various neurotransmitters on different phases and components of the human sexual response cycle arose from clinical observations in patients with psychiatric disorders (La Torre et al., 2013a, La Torre et al., 2013b) that may, however, be confounded by the disorder itself (Angst, 1998, Kennedy and Rizvi, 2009, Soldati, 2016).
We previously investigated the effects of various monoaminergic agents on neural correlates of visual erotic stimulus processing in healthy male subjects by functional magnetic resonance tomography (fMRI). Administration of serotonergic antidepressants was accompanied by a decrease of subjective sexual functions along with attenuated neural activations within brain regions corresponding to emotional and motivational aspects of the sexual response cycle (Abler et al., 2011). As revealed by psychophysiological interaction analyses, downregulation of the human reward system, particularly the nucleus accumbens, under serotonergic agents was mediated by serotonergic enhancement of prefrontal cortex activation (Abler et al., 2012). By contrast, neural activations and subjective sexual functions were unimpaired or even enhanced under bupropion, an antidepressant with a dopaminergic component (Abler et al., 2011). Beside these diverging effects on emotional and motivational aspects of the sexual response cycle, both, serotonergic and dopaminergic antidepressants decreased neural activations corresponding to cognitive components of the sexual response cycle along with diminished behavioral attentional functions (Graf et al., 2013, Graf et al., 2014). To further disentangle monoaminergic modes of action on sexual functioning we recently investigated the effects of the selective noradrenalin reuptake inhibitor (SNRI) reboxetine and the dopamine receptor affine drug amisulpride on neural correlates of visual erotic video stimulus processing in healthy subjects compared to placebo (Graf et al., 2015). In contrast to clinical observations, we found no significant alterations of subjective sexual functions or neural activations under amisulpride compared to placebo presumably due to its pharmacodynamic properties with dopamine agonistic effects under lower dosages as observed in animal studies (Schoemaker et al., 1997) as compared to antidopaminergic effects under higher doses. However, reboxetine was accompanied by a decrease in subjective sexual functioning along with attenuated neural activations upon visual erotic stimulation within the right caudate nucleus indicating disadvantageous effects on motivational components of sexual behavior.
We now examined the effects of the noradrenergic antidepressant reboxetine and the dopamine receptor affine amisulpride compared to placebo on visual static erotic picture stimulation in contrast to former dynamic video stimulation. As this study was conducted within the same study sample as described in Graf et al. (2015), we expected that this investigation would corroborate our previous results and further expand information on the networks involved. We hypothesized that differences in stimulus induced brain activities arising due to presentation mode (Bühler et al., 2008) would allow to complement current results and allow for linking diminished subjective sexual functions in the various domains with distinct neural network components (Graf et al., 2015). Through the application of an established erotic picture paradigm with preceding expectancy periods (Graf et al., 2013), the design also allowed the investigation of neuromodulatory effects of these two agents on attentional components of the sexual response cycle that have not been investigated so far.
Section snippets
Subjects
20 healthy heterosexual male subjects were investigated under sub-chronic administration of amisulpride (AMS), reboxetine (REB) and placebo (PLA) for seven days each in counterbalanced order. One subject was excluded due to newly observed cerebral gliotic lesions resulting in a final sample size of 19 participants (mean age 24.0 years, SD 3.1; range 20–32) in further analyses. Each participant received a full medical evaluation including a medical history, a physical examination and a
Questionnaires, neuropsychological data and subjective ratings
An average CES-D sum-score of 8.0 (SD 6.04) indicated no relevant depressive symptoms in the participants. None of the subjects suffered from severe side-effects under study medication assessed by the UKU side effect scale. An ANOVA for repeated measures revealed no significant treatment effect on sedation or sleepiness immediately after fMRI-scanning (SSS; F(2,36) = 1.47; p = 0.244; for further details see Graf et al. (2015)).
Ratings regarding subjective sexual arousal for erotic pictures (PLA
Discussion
Our previous investigation conducted with dynamic visual erotic stimulation by video-clips (Graf et al., 2015) revealed detrimental effects of the noradrenergic agent REB on subjective sexual functions along with attenuated neural activations in brain regions corresponding to motivational aspects of sexual behavior. In contrast, AMS left subjective sexual functions and neural responses unimpaired. Within the same study sample, we now focused on the effects of these two monoaminergic agents
Role of funding source
CDM was supported by Deutsche Forschungsgemeinschaft, DFG-SFB 779 grant. The DFG had no role in this study, neither in study design or in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. All authors declare that there are no competing financial interests or funding in relation to the work described.
Contributors
The authors Heiko Graf, Martin Walter and Birgit Abler designed the study and wrote the protocol. Authors Heiko Graf and Maike Wiegers managed the literature and the authors Heiko Graf and Georg Grön undertook the statistical analysis. The authors Heiko Graf, Birgit Abler, Coraline D. Metzger and Martin Walter wrote the draft of the manuscript. All authors contributed to and have approved the final manuscript.
Conflict of interest
All authors declare that there are no competing financial interests or funding in relation to the work described.
Acknowledgements
We thank Prof. Dr. C. Hiemke and his staff at the University of Mainz (Germany), Department of Psychiatry and Psychotherapy, for measurements of drug blood serum levels.
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