Relief learning is the association of environmental cues with the cessation of aversive events. While there is increasing knowledge about the neural circuitry mediating relief learning, the respective molecular pathways are not known. Therefore, the aim of the present study was to examine different putative molecular pathways underlying relief learning. To this purpose, male rats were subjected either to relief conditioning or to a pseudo conditioning procedure. Forty-five minutes or 6 h after conditioning, samples of five different brain regions, namely the prefrontal cortex, nucleus accumbens (NAC), dorsal striatum, dorsal hippocampus, and amygdala, were collected. Using quantitative Western blots, the expression level of CREB, pCREB, ERK1/2, pERK1/2, CaMKIIα, MAP2K, PKA, pPKA, Akt, pAkt, DARPP-32, pDARPP-32, 14-3-3, and neuroligin2 were studied. Our analyses revealed that relief conditioned rats had higher CREB phosphorylation in NAC 6 h after conditioning than pseudo conditioned rats. The data further revealed that this CREB phosphorylation was mainly induced by dopamine D1 receptor-mediated activation of PKA, however, other kinases, downstream of the NMDA receptor, may also contribute. Taken together, the present study suggests that CREB phosphorylation, induced by a combination of different molecular pathways downstream of dopamine D1 and NMDA receptors, is essential for the acquisition and consolidation of relief learning.

中文翻译：

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减压调理后伏核中 CREB ​​磷酸化的调节

救济学习是环境线索与厌恶事件停止的关联。虽然关于调节缓解学习的神经回路的知识越来越多，但各自的分子途径尚不清楚。因此，本研究的目的是检查缓解学习背后的不同假定分子途径。为此，对雄性大鼠进行缓解条件反射或伪条件反射程序。调节后 45 分钟或 6 小时，收集了五个不同大脑区域的样本，即前额叶皮层、伏隔核 (NAC)、背侧纹状体、背侧海马和杏仁核。使用定量蛋白质印迹，CREB、pCREB、ERK1/2、pERK1/2、CaMKIIα、MAP2K、PKA、pPKA、Akt、pAkt、DARPP-32、pDARPP-32、14-3-3 和neuroligin2 的表达水平分别为学习了。我们的分析表明，在调节后 6 小时，缓解条件的大鼠在 NAC 中的 CREB ​​磷酸化水平高于假条件大鼠。数据进一步显示，这种 CREB ​​磷酸化主要由多巴胺 D1 受体介导的 PKA 激活诱导，然而，NMDA 受体下游的其他激酶也可能起作用。综上所述，本研究表明，由多巴胺 D1 和 NMDA 受体下游不同分子途径组合诱导的 CREB ​​磷酸化对于获得和巩固缓解学习至关重要。数据进一步显示，这种 CREB ​​磷酸化主要由多巴胺 D1 受体介导的 PKA 激活诱导，然而，NMDA 受体下游的其他激酶也可能起作用。综上所述，本研究表明，由多巴胺 D1 和 NMDA 受体下游不同分子途径组合诱导的 CREB ​​磷酸化对于获得和巩固缓解学习至关重要。数据进一步显示，这种 CREB ​​磷酸化主要由多巴胺 D1 受体介导的 PKA 激活诱导，然而，NMDA 受体下游的其他激酶也可能起作用。综上所述，本研究表明，由多巴胺 D1 和 NMDA 受体下游不同分子途径组合诱导的 CREB ​​磷酸化对于获得和巩固缓解学习至关重要。