The ability of (1DMe)Y8Fa (D.Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2), a selective neuropeptide FF analog resistant to enzymatic degradation, to control morphine-induced analgesia was investigated in rat after microinfusion into the dorsal raphe nucleus and the nucleus parafascicularis of the thalamus. Infusion of (1DMe)Y8Fa (2.5 nmol) in the nucleus raphe dorsalis did not modify the animal response in the tail-immersion test but significantly reversed analgesia induced by coinjected morphine (27 nmol). Similarly, (1DMe)Y8Fa (5 nmol) inhibited morphine effects in the hot-plate test after co-injection into the parafascicular nucleus. Furthermore, (1DMe)Y8Fa injected into the parafascicular nucleus attenuated analgesia induced by morphine injected into the nucleus raphe dorsalis and similarly, the neuropeptide FF analog in the nucleus raphe dorsalis decreased the effects of 27 nmol morphine injected in the parafascicular nucleus. The density of neuropeptide FF receptors did not decrease in the nucleus raphe dorsalis after lesion of serotonergic neurons by 5,7-dihydroxytryptamine. However, after this lesion, (1DMe)Y8Fa injected in the nucleus raphe dorsalis was no longer able to modify analgesic effects of morphine in hot-plate and tail-immersion tests. Similarly, the serotonin (5-HT) depletion induced by a systemic administration of para-chlorophenylalanine did not modify morphine analgesia microinjected into the nucleus raphe dorsalis and the parafascicular nucleus but blocked the ability of (1DMe)Y8Fa to reverse morphine effects in both nuclei. These data show that neuropeptide FF exerts anti-opioid effects directly into both the nucleus raphe dorsalis and the parafascicular nucleus and acts also at distance on opioid functions. Furthermore, anti-opioid effects of neuropeptide FF require functional serotonergic neurons although neuropeptide FF receptors are not carried on these neurons.

中文翻译：

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神经肽FF受体控制吗啡诱导的束旁核和背ra核的镇痛作用。

研究了（1DMe）Y8Fa（D.Tyr-Leu-（NMe）Phe-Gln-Pro-Gln-Arg-Phe-NH2）（一种对酶促降解具有抗性的选择性神经肽FF类似物）控制吗啡诱导的镇痛的能力。在大鼠中，将其微注入丘脑背侧核和丘脑旁束状核。在尾核内注入（1DMe）Y8Fa（2.5 nmol）不会改变动物在尾部浸入试验中的反应，但会显着逆转共注射吗啡（27 nmol）引起的镇痛作用。同样，在共注射到束旁核中后，（1DMe）Y8Fa（5 nmol）在热板试验中抑制了吗啡作用。此外，注射到束旁核中的（1DMe）Y8Fa减弱了由注入吗啡核中的吗啡引起的镇痛作用，并且类似地，背核中的神经肽FF类似物降低了束旁核中注射的27 nmol吗啡的作用。在5,7-二羟基色胺引起的血清素能神经元损伤后，背核中神经肽FF受体的密度没有降低。然而，在此病灶之后，在热板和尾部浸入试验中，注入背心核中的（1DMe）Y8Fa不再能够改变吗啡的止痛效果。同样，对氯苯丙氨酸全身给药引起的5-羟色胺（5-HT）耗竭并没有改变注入到背核和束旁核中的吗啡镇痛作用，但阻止了（1DMe）Y8Fa逆转两个核中吗啡作用的能力。 。这些数据表明，神经肽FF直接在背核和束旁核中发挥抗阿片类药物的作用，并在一定距离上对阿片类药物的功能起作用。此外，神经肽FF的抗阿片样物质作用需要功能性血清素能神经元，尽管这些神经元上不携带神经肽FF受体。