Institute for Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Integrative Neuroscience Program, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Neuropsychopharmacology. 2018 Jul;43(8):1651-1659. doi: 10.1038/s41386-018-0020-1. Epub 2018 Feb 5.
The relief from an aversive event is rewarding. Since organisms are able to learn which environmental cues can cease an aversive event, relief learning helps to better cope with future aversive events. Literature data suggest that relief learning is affected in various psychopathological conditions, such as anxiety disorders. Here, we investigated the role of the mesolimbic dopamine system in relief learning. Using a relief learning procedure in Sprague Dawley rats, we applied a combination of behavioral experiments with anatomical tracing, c-Fos immunohistochemistry, and local chemogenetic and pharmacological interventions to broadly characterize the role of the mesolimbic dopamine system. The present study shows that a specific part of the mesolimbic dopamine system, the projection from the posterior medial ventral tegmental area (pmVTA) to the nucleus accumbens shell (AcbSh), is activated by aversive electric stimuli. 6-OHDA lesions of the pmVTA blocked relief learning but fear learning and safety learning were not affected. Chemogenetic silencing of the pmVTA-AcbSh projection using the DREADD approach, as well as intra-AcbSh injections of the dopamine D2/3 receptor antagonist raclopride inhibited relief learning. Taken together, the present data demonstrate that the dopaminergic pmVTA-AcbSh projection is critical for relief learning but not for similar learning phenomena. This novel finding may have clinical implications since the processing of signals predicting relief and safety is often impaired in patients suffering from anxiety disorders. Furthermore, it may help to better understand psychological conditions like non-suicidal self-injury, which are associated with pain offset relief.
回避性事件带来的缓解是一种奖赏。由于生物体能够学习哪些环境线索可以终止不愉快的事件，因此缓解学习有助于更好地应对未来的不愉快事件。文献数据表明，缓解学习在各种精神病理学状况中受到影响，如焦虑障碍。在这里，我们研究了中脑边缘多巴胺系统在缓解学习中的作用。使用 Sprague Dawley 大鼠的缓解学习程序，我们结合行为实验、解剖追踪、c-Fos 免疫组织化学以及局部化学遗传和药理学干预，广泛表征了中脑边缘多巴胺系统的作用。本研究表明，中脑边缘多巴胺系统的一个特定部分，即来自后内侧腹侧被盖区（pmVTA）到伏隔核壳（AcbSh）的投射，被不愉快的电刺激激活。pmVTA 的 6-OHDA 损伤阻断了缓解学习，但恐惧学习和安全学习不受影响。使用 DREADD 方法对 pmVTA-AcbSh 投射进行化学遗传沉默，以及在 AcbSh 内注射多巴胺 D2/3 受体拮抗剂 raclopride，均抑制了缓解学习。总之，这些数据表明，多巴胺能的 pmVTA-AcbSh 投射对缓解学习至关重要，但对类似的学习现象则不重要。这一新颖的发现可能具有临床意义，因为预测缓解和安全的信号处理在患有焦虑障碍的患者中经常受损。此外，它可能有助于更好地理解与疼痛缓解相关的非自杀性自我伤害等心理状况。
