Tan P P, Chen J C, Li J Y, Liang K W, Wong C H, Huang E Y
Department of Anesthesiology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Republic of China.
Peptides. 1999;20(10):1211-7. doi: 10.1016/s0196-9781(99)00125-4.
Neuropeptide FF (NPFF) has been reported to be an endogenous anti-opioid peptide that has significant effects on morphine tolerance and dependence. In the present study, we examined the chronic effects of NPFF and its synthetic analogs: the putative agonist, PFRFamide, and the putative antagonists, dansyl-PQRamide and PFR(Tic)amide on naloxone-precipitated morphine withdrawal syndromes in rats. After a 5-day co-administration with morphine [5 mg/kg, intraperitoneally (i.p.), twice per day (b.i.d.)] and the tested peptide [intracerebroventricularly (i.c.v.) or i.p., b.i.d.], naloxone (4 mg/kg, i.p.) was given systemically to evaluate the severity of the morphine withdrawal syndromes. Our results revealed that NPFF significantly potentiated the overall morphine withdrawal syndromes and, on the contrary, dansyl-PQRamide attenuated these syndromes. These results clearly indicate that modulation of the NPFF system in the mammalian central nervous system has significant effects on opiate dependence. In addition, morphine withdrawal syndromes could be practically applied as a valid parameter to functionally characterize the putative NPFF agonists and antagonists.
据报道，神经肽FF（NPFF）是一种内源性抗阿片肽，对吗啡耐受性和依赖性有显著影响。在本研究中，我们检测了NPFF及其合成类似物（假定激动剂PFRFamide、假定拮抗剂丹磺酰-PQRamide和PFR（Tic）amide）对大鼠纳洛酮诱发的吗啡戒断综合征的长期影响。在与吗啡[5毫克/千克，腹腔注射（i.p.），每天两次（b.i.d.）]和受试肽[脑室内（i.c.v.）或腹腔注射，每天两次]共同给药5天后，全身给予纳洛酮（4毫克/千克，腹腔注射）以评估吗啡戒断综合征的严重程度。我们的结果显示，NPFF显著增强了整体吗啡戒断综合征，相反，丹磺酰-PQRamide减轻了这些综合征。这些结果清楚地表明，调节哺乳动物中枢神经系统中的NPFF系统对阿片类药物依赖性有显著影响。此外，吗啡戒断综合征可实际用作有效参数，以从功能上表征假定的NPFF激动剂和拮抗剂。
