Gibula-Bruzda Ewa, Marszalek-Grabska Marta, Gawel Kinga, Trzcinska Roza, Silberring Jerzy, Kotlinska Jolanta H
Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
Alcohol. 2017 Nov;64:45-53. doi: 10.1016/j.alcohol.2017.04.005. Epub 2017 Aug 24.
Kissorphin (KSO) is a new peptide derived from kisspeptin-10. This peptide possesses neuropeptide FF (NPFF)-like biological activity in vitro; NPFF, in many cases, inhibits opioid and ethanol effects in rodents. Therefore, the current study explored the influence of KSO on acute ethanol- and morphine-induced hyperactivity, and on the development and expression of locomotor sensitization induced by these drugs. In the present study, sensitization to locomotor effects was induced by repeated exposure to ethanol (2.4 g/kg, intraperitoneally [i.p.], 1 × 4 days) or morphine (10 mg/kg, subcutaneously [s.c.], 1 × 7 days). We found that KSO (1-10 nmol/300 μL, intravenously [i.v.]) did not have an impact on locomotor activity of naïve mice. However, it reduced both acute ethanol- (10 nmol/300 μL) and morphine-induced hyperactivity (3 and 10 nmol/300 μL). Pretreatment of animals with KSO (10 nmol/300 μL), before every ethanol or morphine injection during development of sensitization or before the ethanol or morphine challenge, attenuated the development, as well as the expression of locomotor sensitization to both substances. Moreover, prior administration of the NPFF receptor antagonist RF9 (10 nmol/300 μL, i.v.) inhibited the ability of KSO (10 nmol/300 μL) to reduce the expression of ethanol and morphine sensitization. KSO given alone, at all used doses, did not influence the motor coordination measured via the rotarod test. The results from this study show that KSO effectively attenuated acute and repeated effects of ethanol and morphine. Thus, KSO possesses NPFF-like anti-opioid activity in these behavioral studies.
亲吻素（KSO）是一种源自亲吻素-10的新肽。这种肽在体外具有类似神经肽FF（NPFF）的生物活性；在许多情况下，NPFF可抑制啮齿动物体内的阿片类药物和乙醇效应。因此，本研究探讨了KSO对急性乙醇和吗啡诱导的多动的影响，以及对这些药物诱导的运动敏化的发展和表达的影响。在本研究中，通过重复给予乙醇（2.4 g/kg，腹腔注射[i.p.]，1×4天）或吗啡（10 mg/kg，皮下注射[s.c.]，1×7天）诱导对运动效应的敏化。我们发现，KSO（1-10 nmol/300 μL，静脉注射[i.v.]）对未用药小鼠的运动活动没有影响。然而，它降低了急性乙醇（1,0 nmol/300 μL）和吗啡诱导的多动（3和10 nmol/300 μL）。在敏化发展过程中每次乙醇或吗啡注射前或乙醇或吗啡激发前，用KSO（10 nmol/300 μL）预处理动物，可减弱对这两种物质的运动敏化的发展以及表达。此外，预先给予NPFF受体拮抗剂RF9（10 nmol/300 μL，静脉注射）可抑制KSO（10 nmol/300 μL）降低乙醇和吗啡敏化表达的能力。单独给予KSO，在所有使用剂量下，均不影响通过转棒试验测量的运动协调性。本研究结果表明，KSO有效减弱了乙醇和吗啡的急性和重复效应。因此，在这些行为学研究中，KSO具有类似NPFF的抗阿片类活性。
