Nociceptin/orphanin FQ decreases serotonin efflux in the rat brain but in contrast to a kappa-opioid has no antagonistic effect on mu-opioid-induced increases in serotonin efflux.
Nociceptin/orphanin FQ decreases serotonin efflux in the rat brain but in contrast to a kappa-opioid has no antagonistic effect on mu-opioid-induced increases in serotonin efflux.
复制标题
伤害感受肽/孤啡肽 FQ 减少大鼠大脑中的血清素流出，但与 kappa-阿片类药物相反，对 mu-阿片类药物诱导的血清素流出增加没有拮抗作用。
DOI：
10.1016/j.neuroscience.2007.02.011
复制
发表时间：
2007
期刊：
影响因子：
3.3
通讯作者：
Auerbach,SB
中科院分区：
文献类型：
--
作者：
Tao,R;Ma,Z;Thakkar,MM;McCarley,RW;Auerbach,SB
与 κ-阿片类药物类似，痛敏肽/孤啡肽 FQ (OFQ) 具有抗 μ-阿片类药物作用。这可能涉及控制中缝背核 (DRN) 中投射到伏隔核 (NAcc) 的 5-HT 神经元的电路内部的相互作用。为了检验这一假设，我们比较了 OFQ 和 κ-阿片类药物对自由行为大鼠中枢神经系统 5-HT 流出的影响。首先，将 OFQ (30–300 μM) 注入 DRN 120 分钟，剂量依赖性地减少 DRN 中的 5-HT 流出。阿片受体样 1 (ORL-1) 拮抗剂 [Nphe1]nociceptin(1–13)NH2 可阻断这种作用。使用双探针微透析，我们观察到将 OFQ (300 μM) 注入 DRN 120 分钟，导致 DRN 和 NAcc 中 5-HT 流出量平行减少，表明 DRN 中的 ORL-1 受体抑制投射到 NAcc 的血清素能神经元。此外，在 OFQ（30-300 μM）输注至 NAcc 期间，NAcc 中的 5-HT 流出量呈剂量依赖性减少。这表明 OFQ 可以通过抑制 DRN 中的血清素能神经元和刺激 NAcc 中的 ORL-1 受体来减少 NAcc 中的 5-HT 外流。与 OFQ 类似，将 κ-阿片类药物 U-50,488 (300 μM) 和强啡肽 A(1–13) (300 μM) 注入 DRN 120 分钟，减少 DRN 中的 5-HT 外流。这种作用只能被κ-阿片受体拮抗剂nor-BNI 阻断。最后，我们比较了 OFQ 和 U-50,488 阻止 μ-阿片类药物诱导的 5-HT 增加的能力。 κ-阿片类药物 U-50,488 (1000 μM) 减弱了 DRN 中 μ-阿片类药物激动剂内吗啡肽-1 (300 μM) 诱导的 5-HT 增加。相比之下，OFQ (300–1000 μM) 不会改变 μ-阿片类药物诱导的 5-HT 外流增加。总之，κ-阿片类药物和 OFQ 均减少 CNS 中的 5-HT 流出。然而，与κ-阿片类药物相反，κ-阿片类药物可逆转μ-阿片类药物诱导的5-HT外流增加，OFQ的抗μ-阿片类药物作用显然不涉及在我们的实验条件下5-HT传输的变化。
Similar to κ-opioids, nociceptin/orphanin FQ (OFQ) exerts anti-μ-opioid actions. This may involve interactions within the circuitry controlling 5-HT neurons in the dorsal raphe nucleus (DRN) that project to the nucleus accumbens (NAcc). To test this hypothesis, we compared the effects of OFQ and κ-opioids on 5-HT efflux in the CNS of freely behaving rats. First, OFQ (30–300 μM) infused into the DRN for 120 min dose-dependently decreased 5-HT efflux in the DRN. The opioid receptor-like 1 (ORL-1) antagonist [Nphe1]nociceptin(1–13)NH2blocked this effect. Using dual-probe microdialysis we observed that OFQ (300 μM) infused into the DRN for 120 min produced parallel decreases in 5-HT efflux in the DRN and NAcc, suggesting that ORL-1 receptors in the DRN inhibit serotonergic neurons projecting to the NAcc. Also, 5-HT efflux in the NAcc was dose-dependently decreased during OFQ (30–300 μM) infusion into the NAcc. This suggests that OFQ can reduce 5-HT efflux in the NAcc both by inhibiting serotonergic neurons in the DRN and by stimulating ORL-1 receptors in the NAcc. Similar to OFQ, the κ-opioids U-50,488 (300 μM) and dynorphin A(1–13) (300 μM) infused into the DRN for 120 min decreased 5-HT efflux in the DRN. This effect was blocked only by the κ-opioid receptor antagonist nor-BNI. Lastly, we compared the ability of OFQ and U-50,488 to block μ-opioid-induced increases in 5-HT. The κ-opioid U-50,488 (1000 μM) attenuated the increase in 5-HT induced by the μ-opioid agonist endomorphin-1 (300 μM) in the DRN. In contrast, OFQ (300–1000 μM) did not alter μ-opioid-induced increases in 5-HT efflux. In summary, κ-opioids and OFQ both decreased 5-HT efflux in the CNS. However, in contrast to κ-opioids, which reversed μ-opioid-induced increases in 5-HT efflux, the anti-μ-opioid effects of OFQ apparently do not involve changes in 5-HT transmission under our experimental conditions.