Bergado Acosta Jorge R, Kahl Evelyn, Kogias Georgios, Uzuneser Taygun C, Fendt Markus
Institute for Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, Germany.
Institute for Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, Germany; Integrative Neuroscience Program, Otto-von-Guericke University Magdeburg, Germany.
Neuropharmacology. 2017 Mar 1;114:58-66. doi: 10.1016/j.neuropharm.2016.11.022. Epub 2016 Nov 26.
Relief learning is the association of a stimulus with the offset of an aversive event. Later, the now conditioned relief stimulus induces appetitive-like behavioral changes. We previously demonstrated that the NMDA receptors within the nucleus accumbens (NAC) are involved in relief learning. The NAC is also important for reward learning and it has been shown that reward learning is mediated by an interaction of accumbal dopamine and NMDA glutamate receptors. Since conditioned relief has reward-like properties, we hypothesized that (a) acquisition of relief learning requires the activation of dopamine D1 receptors in the NAC, and (b) if D1 receptors are involved in this process as expected, a concurrent dopamine D1 and NMDA receptor activation may mediate this learning. The present study tested these hypotheses. Therefore, rats received intra-NAC injections of the dopamine D1 receptor antagonist SCH23390 and the NMDA antagonist AP5, either separately or together, at different time points of a relief conditioning procedure. First, we showed that SCH23390 dose-dependently blocked acquisition and the expression of conditioned relief. Next, we demonstrated that co-injections of SCH23390 and AP5 into the NAC, at doses that were ineffective when applied separately, blocked acquisition but not consolidation or expression of relief learning. Notably, neither of the injections affected the locomotor response of the animals to the aversive stimuli suggesting that their perception is not changed. This data indicates that a co-activation of dopamine D1 and NMDA receptors in the NAC is required for acquisition of relief learning.
缓解学习是指将一种刺激与厌恶事件的终止联系起来。随后，这个现在已形成条件的缓解刺激会引发类似欲求的行为变化。我们之前证明伏隔核（NAC）内的NMDA受体参与了缓解学习。伏隔核对于奖赏学习也很重要，并且已经表明奖赏学习是由伏隔核多巴胺和NMDA谷氨酸受体的相互作用介导的。由于条件性缓解具有类似奖赏的特性，我们推测：（a）缓解学习的获得需要激活伏隔核中的多巴胺D1受体；（b）如果D1受体如预期那样参与这个过程，那么多巴胺D1受体和NMDA受体的同时激活可能介导这种学习。本研究对这些推测进行了验证。因此，在缓解条件化程序的不同时间点，大鼠接受了向伏隔核内单独或同时注射多巴胺D1受体拮抗剂SCH23390和NMDA拮抗剂AP5。首先，我们表明SCH23390剂量依赖性地阻断了条件性缓解的获得和表达。接下来，我们证明，将SCH23390和AP5共同注射到伏隔核中，在单独注射时无效的剂量下，会阻断条件性缓解的获得，但不会阻断巩固或表达。值得注意的是，两种注射都没有影响动物对厌恶刺激的运动反应，这表明它们的感知没有改变。这些数据表明，伏隔核中多巴胺D1受体和NMDA受体的共同激活是缓解学习获得所必需的。
