Department of Pathophysiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Behav Brain Res. 2012 Mar 17;228(2):388-91. doi: 10.1016/j.bbr.2011.12.022. Epub 2011 Dec 19.
MZ-4-71 is an antagonist of growth hormone-releasing hormone (GH-RH) which suppresses the secretion of GH-RH. It has been shown that MZ-4-71 has antidepressive-like effects in a modified forced swimming test (FST) in mice, exerts anxiolytic effects in an elevated plus maze test, improves memory consolidation in passive avoidance learning, and corrects the impairment of memory consolidation caused by β-amyloid 25-35 in mice. However, little is known about the mechanisms of action of MZ-4-71 on brain functions. The involvement of the adrenergic, serotonergic, cholinergic, dopaminergic or GABA-ergic receptors in the antidepressant-like action of MZ-4-71 (1.0 μg/2 μl, intracerebroventricular (i.c.v.)) was studied in a modified mouse forced swimming test (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, a non-selective muscarinic acetylcholine receptor antagonist, atropine, a D2, D3, D4 dopamine receptor antagonist, haloperidol or a γ-aminobutyric acid subunit A (GABA-A) receptor antagonist bicuculline. Phenoxybenzamine, prazosin, methysergide, cyproheptadine and atropine prevented the effects of MZ-4-71 on the immobility, the climbing and the swimming times. Yohimbine, propranolol, haloperidol and bicuculline did not change the effects of MZ-4-71. The results demonstrated that the antidepressant-like effects of MZ-4-71 in this modified mouse FST are mediated, at least in part, by the an interaction of the α1-adrenergic, 5-HT1/5-HT2 serotonergic, and muscarinic acetylcholine receptors.
MZ-4-71 是生长激素释放激素 (GH-RH) 的拮抗剂，可抑制 GH-RH 的分泌。研究表明，MZ-4-71 在改良的强迫游泳试验 (FST) 中具有抗抑郁样作用，在高架十字迷宫试验中具有抗焦虑作用，在被动回避学习中改善记忆巩固，纠正β-淀粉样蛋白 25-35 在小鼠中引起的记忆巩固障碍。然而，关于 MZ-4-71 对大脑功能的作用机制知之甚少。在改良的小鼠强迫游泳试验 (FST) 中研究了 MZ-4-71（1.0 μg/2 μl，侧脑室注射 (i.c.v.)) 的抗抑郁样作用涉及肾上腺素能、5-羟色胺能、胆碱能、多巴胺能或 GABA-ergic 受体。小鼠用非选择性α-肾上腺素能受体拮抗剂苯氧苄胺、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 混合 5-羟色胺能受体拮抗剂甲硫哒嗪、非选择性 5-HT2 5-羟色胺能受体拮抗剂赛庚啶、非选择性毒蕈碱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-氨基丁酸亚基 A(GABA-A) 受体拮抗剂印防己毒素预处理。苯氧苄胺、哌唑嗪、甲硫哒嗪、赛庚啶和阿托品阻止了 MZ-4-71 对不动性、攀爬和游泳时间的影响。育亨宾、普萘洛尔、氟哌啶醇和印防己毒素未改变 MZ-4-71 的作用。结果表明，MZ-4-71 在这种改良的小鼠 FST 中的抗抑郁样作用至少部分通过与α1-肾上腺素能、5-HT1/5-HT2 5-羟色胺能和毒蕈碱乙酰胆碱受体的相互作用介导。
