Graf Heiko, Wiegers Maike, Metzger Coraline D, Walter Martin, Abler Birgit
Department of Psychiatry and Psychotherapy III, Ulm University, Ulm, Germany.
Department of Psychiatry, Otto von Guericke University, Magdeburg, Germany.
Front Psychiatry. 2018 Jul 31;9:346. doi: 10.3389/fpsyt.2018.00346. eCollection 2018.
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 ( < 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.
我们最近在健康受试者中,通过视觉色情刺激,研究了去甲肾上腺素能抗抑郁药瑞波西汀和抗精神病药阿立哌唑与安慰剂相比,对初级强化物神经相关性的影响。然而,阿立哌唑对主观性性功能和相应的神经激活没有影响,而在瑞波西汀作用下,伏隔核内的神经激活减弱,同时性行为功能也有所下降。然而,考虑到去甲肾上腺素能系统在由预测误差处理介导的奖励相关学习中对多巴胺系统的补充作用,瑞波西汀对奖励系统的整体抑制作用似乎并不直观。因此,我们再次通过功能磁共振成像(fMRI)对17名平均年龄为23.8岁的健康男性样本进行了研究,以探索去甲肾上腺素能系统对神经奖励预测误差信号的影响。参与者在随机、双盲、受试者内交叉设计中,分别服用瑞波西汀(4毫克/天)、阿立哌唑(200毫克/天)和安慰剂,各服用7天。在fMRI期间,我们使用既定的金钱激励任务,通过独立的感兴趣区域(ROI)分析解剖学掩膜,评估双侧伏隔核内的神经奖励期望和预测误差信号。还对色情图片范式的同一ROI内的激活进行了评估。与安慰剂相比,我们通过瑞波西汀作用下视觉性刺激期间伏隔核内显著(<0.05 FWE校正)减弱的激活,证实了我们之前对选定ROI进行全脑分析的结果。然而,与安慰剂相比,瑞波西汀作用下伏隔核内与预测误差处理和金钱奖励期望相关的激活未受影响,奖励任务中的反应时间也未受影响。与安慰剂相比,阿立哌唑对这两项任务的神经激活和行为处理均无改变。在视觉色情刺激期间伏隔核内观察到的神经激活减弱,以及神经预测误差和金钱奖励期望处理未受影响,这为去甲肾上腺素能药物瑞波西汀根据是否存在诸如色情刺激等初级强化物(与金钱奖励等次级强化物相比)对神经奖励系统进行差异调节提供了证据。