Role of glutamatergic receptors located in the nucleus raphe magnus on antinociceptive effect of morphine microinjected into the nucleus cuneiformis of rat
Role of glutamatergic receptors located in the nucleus raphe magnus on antinociceptive effect of morphine microinjected into the nucleus cuneiformis of rat
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DOI：
10.1016/j.neulet.2007.09.003
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发表时间：
2007-10-29
影响因子：
2.5
通讯作者：
Komaki, Alireza
中科院分区：
文献类型：
--
作者：
Haghparast, Abbas;Soltani-Hekmat, Ava;Komaki, Alireza
楔状核（CnF）中的神经元位于导水管周围灰质的腹外侧，投射到中缝大核（NRM），这是下行疼痛调节的关键髓质中继，并且与阿片类药物诱导的镇痛密切相关。先前的研究表明，CnF 显微注射吗啡的镇痛反应可以通过 CnF 内谷氨酸能受体的特定亚型来调节。在本研究中，我们评估了 NRM 内广泛分布的 NMDA 和红藻氨酸/AMPA 受体对 CnF 引起的吗啡诱导的镇痛作用的作用。使用105只体重250-300g的雄性Wistar大鼠。将0.5μl盐水中的吗啡（10、20和40μg）和NMDA受体拮抗剂MK-801（10μg）或红藻氨酸/AMPA受体拮抗剂DNQX（0.5μg）分别立体定位显微注射到CnF和NRM中。使用自动甩尾镇痛仪以设定的时间间隔（显微注射后 2、7、12、17、22、27 分钟）测量甩尾反应的潜伏期。结果表明，将吗啡显微注射到 CnF 中会导致甩尾潜伏期 (TFL) 的增加，剂量依赖性。在吗啡注射到 CnF 前一分钟，将 MK-801 显微注射到 NRM 中，显着减弱吗啡的镇痛作用。另一方面，将 DNQX 显微注射到 NRM 中，在将吗啡局部应用到 CnF 中后，TFL 显着增加。我们认为，CnF 引起的吗啡相关的镇痛作用部分是由 NRM 水平的 NMDA 受体介导的，而红藻氨酸/AMPA 受体在同一途径中具有净抑制影响。 (c) 2007 Elsevier Ireland Ltd. 保留所有权利。
Neurons in the nucleus cuneiformis (CnF), located just ventrolateral to the periaqueductal gray, project to medullary nucleus raphe magnus (NRM), which is a key medullary relay for descending pain modulation and is critically involved in opioid-induced analgesia. Previous studies have shown that antinociceptive response of CnF-microinjected morphine can be modulated by the specific subtypes of glutamatergic receptors within the CnF. In this study, we evaluated the role of NMDA and kainate/AMPA receptors that are widely distributed within the NRM on morphine-induced antinociception elicited from the CnF. Hundred and five male Wistar rats weighing 250-300 g were used. Morphine (10, 20 and 40 mu g) and NMDA receptor antagonist, MK-801 (10 mu g) or kainate/AMPA receptor antagonist, DNQX (0.5 mu g) in 0.5 mu l saline were stereotaxically microinjected into the CnF and NRM, respectively. The latency of tail-flick response was measured at set intervals (2, 7, 12, 17, 22, 27 min after microinjection) by using an automated tail-flick analgesiometer. The results showed that morphine microinjection into the CnF dose-dependently causes increase in tail-flick latency (TFL). MK-801 microinjected into the NRM, just I min before morphine injection into the CnF, significantly attenuated antinociceptive effects of morphine. On the other hand, DNQX microinjected into the NRM, significantly increased TFL after local application of morphine into the CnF. We suggest that morphine related antinociceptive effect elicited from the CnF is mediated, in part, by NMDA receptor at the level of the NRM whereas kainite/AMPA receptor has a net inhibitory influence at the same pathway. (c) 2007 Elsevier Ireland Ltd. All rights reserved.