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.

中文翻译：

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中脑边缘多巴胺系统在缓解学习中的作用。


从令人厌恶的事件中解脱出来是有益的。由于生物体能够了解哪些环境线索可以阻止厌恶事件，因此缓解学习有助于更好地应对未来的厌恶事件。文献数据表明，缓解学习会受到各种精神病理状况的影响，例如焦虑症。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。我们在 Sprague Dawley 大鼠中采用缓解学习程序，将行为实验与解剖追踪、c-Fos 免疫组织化学以及局部化学遗传学和药理学干预相结合，以广泛表征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，即从后内侧腹侧被盖区（pmVTA）到伏隔核壳（AcbSh）的投影，被厌恶性电刺激激活。 pmVTA 的 6-OHDA 损伤阻碍了缓解学习，但恐惧学习和安全学习不受影响。使用 DREADD 方法对 pmVTA-AcbSh 投射进行化学遗传学沉默，以及在 AcbSh 内注射多巴胺 D2/3 受体拮抗剂雷氯必利抑制缓解学习。综上所述，目前的数据表明，多巴胺能 pmVTA-AcbSh 投影对于缓解学习至关重要，但对于类似的学习现象则不然。这一新发现可能具有临床意义，因为患有焦虑症的患者预测缓解和安全的信号处理通常会受到损害。此外，它可能有助于更好地了解非自杀性自伤等心理状况，这些状况与疼痛抵消缓解有关。