Selective serotonin reuptake inhibitor treatment retunes emotional valence in primate ventral striatum
Selective serotonin reuptake inhibitor treatment retunes emotional valence in primate ventral striatum
复制标题
选择性血清素再摄取抑制剂治疗可重新调整灵长类腹侧纹状体的情绪效价
作者：
B. Pasquereau;G. Drui;Y. Saga;Augustin Richard;Mathilde Millot;E. Météreau;V. Sgambato;P. Tobler;L. Tremblay
选择性5 -羟色胺再摄取抑制剂（SSRIs）被广泛用于治疗具有情感偏见的精神疾病，如抑郁和焦虑。ssri类药物如何对与生活事件相关的情绪发挥有益作用尚不清楚。在这里，我们询问SSRI氟西汀的有效性是否以及如何以腹侧纹状体的神经机制为基础。为了解决这些问题，我们研究了猴子在接近-回避任务中腹侧纹状体神经元的尖峰活动，在该任务中，分配给感觉刺激的价被操纵。在氟西汀治疗前和4周期间测量对阳性和阴性事件的神经反应。我们进行了PET扫描，以确认氟西汀在治疗剂量下与腹侧纹状体结合。在我们的猴子中，氟西汀促进了奖励和避免惩罚的方法。这些有益作用与纹状体神经元的强直和相位活动的变化有关。氟西汀增加纹状体神经元的自发放电率，并增加对奖励和惩罚作出反应的细胞数量，反映了药物引起的情绪价值信息处理的积极转变。这些发现揭示了SSRI治疗如何影响编码正、负效价的腹侧纹状体神经元和情绪信息的纹状体信号传导。除了在食欲加工中起关键作用外，我们的研究结果还揭示了腹侧纹状体在厌恶加工中的参与。综上所述，腹侧纹状体似乎在SSRIs对精神疾病中常见的情绪加工偏差的作用中起着核心作用。
Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat psychiatric disorders with affective biases such as depression and anxiety. How SSRIs exert a beneficial action on emotions associated with life events is still unknown. Here we ask whether and how the effectiveness of the SSRI fluoxetine is underpinned by neural mechanisms in the ventral striatum. To address these issues, we studied the spiking activity of neurons in the ventral striatum of monkeys during an approach-avoidance task in which the valence assigned to sensory stimuli was manipulated. Neural responses to positive and negative events were measured before and during a 4-week treatment with fluoxetine. We conducted PET scans to confirm that fluoxetine binds within the ventral striatum at a therapeutic dose. In our monkeys, fluoxetine facilitated approach of rewards and avoidance of punishments. These beneficial effects were associated with changes in tonic and phasic activities of striatal neurons. Fluoxetine increased the spontaneous firing rate of striatal neurons and amplified the number of cells responding to rewards versus punishments, reflecting a drug-induced positive shift in the processing of emotionally valenced information. These findings reveal how SSRI treatment affects ventral striatum neurons encoding positive and negative valence and striatal signaling of emotional information. In addition to a key role in appetitive processing, our results shed light on the involvement of the ventral striatum in aversive processing. Together, the ventral striatum appears to play a central role in the action of SSRIs on emotion processing biases commonly observed in psychiatric disorders.
DOI：
10.1176/appi.ajp.2012.12010014
发表时间：
2013-02
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Heller AS;Johnstone T;Light SN;Peterson MJ;Kolden GG;Kalin NH;Davidson RJ
通讯作者：
Davidson RJ
DOI：
10.1016/s2215-0366(17)30015-9
发表时间：
2017-05
期刊：
The lancet. Psychiatry
影响因子：
--
作者：
Harmer CJ;Duman RS;Cowen PJ
通讯作者：
Cowen PJ