Department of Psychiatry, University of Ulm, 89075 Ulm, Germany.
J Neurosci. 2012 Jan 25;32(4):1329-35. doi: 10.1523/JNEUROSCI.5826-11.2012.
Recently, functional interactions between anteroventral prefrontal cortex and nucleus accumbens (NAcc) have been shown to relate to behavior counteracting reward-desiring (Diekhof and Gruber, 2010). Downregulation of the reward system by serotonin has also been suggested as the mode of action accounting for unsatisfactory effects of serotonin reuptake inhibitors (SSRIs) such as insufficient alleviation or even increase of anhedonia, and loss of interest. However, understanding of the in vivo mechanisms of SSRI-related alteration of the human reward system is still incomplete. Using functional magnetic resonance imaging (fMRI) within a double-blind cross-over within-subjects study design and administering the SSRI paroxetine, the dopamine/norepinephrine reuptake inhibitor bupropione, and placebo for 7 d each, we investigated a group of 18 healthy male subjects. Under paroxetine, subjects showed significantly decreased activation of the bilateral NAcc during processing of primary rewards (erotic videos), but not under bupropion. Similar to the previous study, analysis of psychophysiological interactions revealed that this downregulation relied on negative interactions between left and right NAcc fMRI signals and the bilateral anteroventral prefrontal cortex that now were significantly enhanced under paroxetine and reduced under bupropion. Individual drug-dependent modulations of interacting brain regions were significantly associated with individual expressions of impulsivity as a personality trait. Our results corroborate and extend previous insights on interregional crosstalk from secondary to primary rewards and demonstrate parallels between active inhibitory control of and serotonergic effects on the dopaminergic reward system's activity.
最近，研究表明腹侧前额叶皮层和伏隔核（NAcc）之间的功能相互作用与对抗奖励欲望的行为有关（Diekhof 和 Gruber，2010）。也有人认为，血清素对奖励系统的下调是解释 5-羟色胺再摄取抑制剂（SSRIs）如舍曲林等效果不理想的作用模式，这些药物的效果表现为快感缺失的缓解不足，甚至增加，以及兴趣丧失。然而，对 SSRI 相关的人类奖励系统改变的体内机制的理解仍然不完整。在一项双盲交叉自身对照研究设计中，使用功能磁共振成像（fMRI），并在 7 天内分别给予 SSRI 帕罗西汀、多巴胺/去甲肾上腺素再摄取抑制剂安非他酮和安慰剂，我们研究了 18 名健康男性受试者。在帕罗西汀治疗下，受试者在处理初级奖励（色情视频）时双侧 NAcc 的激活明显降低，但在安非他酮治疗下则没有。与之前的研究相似，心理生理交互分析表明，这种下调依赖于左、右 NAcc fMRI 信号与双侧腹侧前额叶皮层之间的负交互作用，而现在这些负交互作用在帕罗西汀治疗下显著增强，在安非他酮治疗下显著减弱。个体药物依赖性地调节相互作用的大脑区域与个体冲动性人格特质的表达显著相关。我们的结果证实并扩展了之前关于从二级奖励到一级奖励的区域间串扰的研究结果，并证明了主动抑制控制与 5-羟色胺对多巴胺奖励系统活动的影响之间的相似性。
