Activations of muscarinic M(1) receptors in the anterior cingulate cortex contribute to the antinociceptive effect via GABAergic transmission.
Activations of muscarinic M(1) receptors in the anterior cingulate cortex contribute to the antinociceptive effect via GABAergic transmission.
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DOI：
10.1177/1744806917692330
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发表时间：
2017-01
期刊：
影响因子：
3.3
通讯作者：
Ueno S
中科院分区：
文献类型：
--
作者：
Koga K;Matsuzaki Y;Honda K;Eto F;Furukawa T;Migita K;Irie K;Mishima K;Ueno S
胆碱能系统调节突触传递，导致伤害性行为的发生。前扣带皮层是参与伤害性感受和慢性疼痛的关键皮层区域。然而，胆碱能系统的激活对皮层区的伤害性感受的影响仍然是未知的。本研究采用行为学、免疫组织化学和电生理学等综合方法，探讨了成年大鼠前扣带皮层胆碱能受体的激活对伤害性行为的调节作用。我们发现，毒蕈碱M1受体在前扣带皮层中明确表达。使用行为测试，我们确定，微量注射选择性毒蕈碱M1受体激动剂McN-A-343到前扣带回皮质剂量依赖性地增加机械阈值。相比之下，将McN-A-343局部注射到前扣带皮层中显示出正常的运动功能。微量注射M1受体拮抗剂哌仑西平可阻断McN-A-343的抗伤害效应。哌仑西平单独进入前扣带回皮质降低了机械阈值。前扣带皮层局部注射GABAA受体拮抗剂荷包牡丹碱也可抑制McN-A-343诱导的抗伤害效应，降低机械阈值。最后，我们使用全细胞膜片钳记录进一步测试M1受体的激活是否可以调节GABA能传递。M1受体的激活增强自发和微型抑制性突触后电流的频率以及自发抑制性突触后电流的振幅在前扣带皮层。这些结果表明，毒蕈碱M1受体的激活部分增加了机械阈值，通过增加GABA能递质的释放，促进GABA能在前扣带皮层的传输。
Cholinergic systems regulate the synaptic transmission resulting in the contribution of the nociceptive behaviors. Anterior cingulate cortex is a key cortical area to play roles in nociception and chronic pain. However, the effect of the activation of cholinergic system for nociception is still unknown in the cortical area. Here, we tested whether the activation of cholinergic receptors can regulate nociceptive behaviors in adult rat anterior cingulate cortex by integrative methods including behavior, immunohistochemical, and electrophysiological methods. We found that muscarinic M1 receptors were clearly expressed in the anterior cingulate cortex. Using behavioral tests, we identified that microinjection of a selective muscarinic M1 receptors agonist McN-A-343 into the anterior cingulate cortex dose dependently increased the mechanical threshold. In contrast, the local injection of McN-A-343 into the anterior cingulate cortex showed normal motor function. The microinjection of a selective M1 receptors antagonist pirenzepine blocked the McN-A-343-induced antinociceptive effect. Pirenzepine alone into the anterior cingulate cortex decreased the mechanical thresholds. The local injection of the GABAA receptors antagonist bicuculline into the anterior cingulate cortex also inhibited the McN-A-343-induced antinociceptive effect and decreased the mechanical threshold. Finally, we further tested whether the activation of M1 receptors could regulate GABAergic transmission using whole-cell patch-clamp recordings. The activation of M1 receptors enhanced the frequency of spontaneous and miniature inhibitory postsynaptic currents as well as the amplitude of spontaneous inhibitory postsynaptic currents in the anterior cingulate cortex. These results suggest that the activation of muscarinic M1 receptors in part increased the mechanical threshold by increasing GABAergic transmitter release and facilitating GABAergic transmission in the anterior cingulate cortex.