Tanaka Masaru, Telegdy Gyula
Department of Pathophysiology, MTA-SZTE Neuroscience Research Group, Faculty of Medicine, University of Szeged, Semmelweis 1, 6701 Szeged, Hungary.
Department of Pathophysiology, MTA-SZTE Neuroscience Research Group, Faculty of Medicine, University of Szeged, Semmelweis 1, 6701 Szeged, Hungary.
Behav Brain Res. 2014 Feb 1;259:196-9. doi: 10.1016/j.bbr.2013.11.005. Epub 2013 Nov 13.
Neuromedin U (NmU) is a widely distributed and multifunctional peptide in the central nervous system and the peripheral tissues. Little is know about the mechanisms of NmU on brain functions. The rodent isoform of the NmU, NmU-23, has been shown to have anxiolytic effects involved in the β-adrenergic and cholinergic nervous systems in elevated plus maze test. NmU-23 was tested for antidepressant-like effects in modified forced swimming test (FST) in mice and furthermore, the involvement of the adrenergic, serotonergic, cholinergic, dopaminergic or gaba-ergic receptors in the antidepressant-like effect of NmU-23 was studied in modified mice FST. Mice were pretreated with a non-selective α-adrenergic receptor antagonist phenoxybenzamine, an α1/α2β-adrenergic receptor antagonist, prazosin, an α2-adrenergic receptor antagonist, yohimbine, a β-adrenergic receptor antagonist, propranolol, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, nonselective muscarinic acetylcholine receptor antagonist, atropine, D2,D3,D4 dopamine receptor antagonist, haloperidol or γ-aminobutyric acid subunit A (GABAA) receptor antagonist, bicuculline. NmU-23 showed the antidepressant-like effects by decreasing the immobility time and increasing the climbing and swimming time. Prazosin, haloperidol, and bicuculline prevented the effects of NmU-23 on the climbing and swimming time. Methysergide and cyproheptadine prevented the effects of NmU-23 on the immobility, swimming and climbing time. Atropine prevented the effects of NmU-23 on the climbing time. Phenoxybenzamine, yohimbine and propranolol did not change the effects of NmU-23. The results demonstrated that the antidepressant-like effect of NmU-23 is mediated, at least in part, by an interaction of the α2-adrenergic, 5-HT1-2 serotonergic, D2,D3,D4 dopamine receptor, muscarinic acetylcholine receptors and γ-aminobutyric acid subunit A (GABAA) receptor in a modified mouse FST.
神经介素U（NmU）是一种在中枢神经系统和外周组织中广泛分布且具有多种功能的肽。关于NmU对脑功能的作用机制知之甚少。在高架十字迷宫试验中，已证实啮齿动物的NmU同工型NmU - 23具有涉及β - 肾上腺素能和胆碱能神经系统的抗焦虑作用。在改良强迫游泳试验（FST）中对小鼠测试了NmU - 23的抗抑郁样作用，此外，还在改良小鼠FST中研究了肾上腺素能、血清素能、胆碱能、多巴胺能或γ - 氨基丁酸能受体在NmU - 23抗抑郁样作用中的参与情况。用非选择性α - 肾上腺素能受体拮抗剂酚苄明、α1/α2β - 肾上腺素能受体拮抗剂哌唑嗪、α2 - 肾上腺素能受体拮抗剂育亨宾、β - 肾上腺素能受体拮抗剂普萘洛尔、5 - HT1/5 - HT2血清素能混合受体拮抗剂麦角新碱、非选择性5 - HT2血清素能受体拮抗剂赛庚啶、非选择性毒蕈碱型乙酰胆碱受体拮抗剂阿托品、D2、D3、D4多巴胺受体拮抗剂氟哌啶醇或γ - 氨基丁酸A亚基（GABAA）受体拮抗剂荷包牡丹碱对小鼠进行预处理。NmU - 23通过减少不动时间并增加攀爬和游泳时间显示出抗抑郁样作用。哌唑嗪、氟哌啶醇和荷包牡丹碱可阻止NmU - 23对攀爬和游泳时间的影响。麦角新碱和赛庚啶可阻止NmU - 23对不动、游泳和攀爬时间的影响。阿托品可阻止NmU - 23对攀爬时间的影响。酚苄明、育亨宾和普萘洛尔不改变NmU - 23的作用。结果表明，在改良小鼠FST中，NmU - 23的抗抑郁样作用至少部分是由α2 - 肾上腺素能、5 - HT1 - 2血清素能、D2、D3、D4多巴胺受体、毒蕈碱型乙酰胆碱受体和γ - 氨基丁酸A亚基（GABAA）受体的相互作用介导的。
