Bahi Amine, Schwed Johannes Stephan, Walter Miriam, Stark Holger, Sadek Bassem
Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Institut für Pharmazeutische Chemie, Biozentrum, Johann Wolfgang Goethe University, Frankfurt, Germany ; Heinrich Heine University Duesseldorf, Institut fuer Pharmazeutische and Medizinische Chemie, Düsseldorf, Germany.
Drug Des Devel Ther. 2014 May 28;8:627-37. doi: 10.2147/DDDT.S63088. eCollection 2014.
Previous studies have suggested a potential link between histamine H₃ receptors (H₃R) signaling and anxiolytic-like and antidepressant-like effects. The aim of this study was to investigate the acute effects of ST-1283, a novel H₃R antagonist, on anxiety-related and depression-related behaviors in comparison with those of diazepam and fluoxetine. The effects of ST-1283 were evaluated using the elevated plus maze test, open field test, marbles burying test, tail suspension test, novelty suppressed feeding test, and forced swim test in male C57BL/6 mice. The results showed that, like diazepam, ST-1283 (7.5 mg/kg) significantly modified all the parameters observed in the elevated plus maze test. In addition, ST-1283 significantly increased the amount of time spent in the center of the arena without altering general motor activity in the open field test. In the same vein, ST-1283 reduced the number of buried marbles as well as time spent digging in the marbles burying test. The tail suspension test and forced swim test showed that ST-1283 was able to reduce immobility time, like the recognized antidepressant drug fluoxetine. In the novelty suppressed feeding test, treatment with ST-1283 decreased latency to feed with no effect on food intake in the home cage. Importantly, pretreatment with the H₃R agonist R-α-methylhistamine abrogated the anxiolytic and antidepressant effects of ST-1283. Taken together, the present series of studies demonstrates the novel effects of this newly synthesized H₃R antagonist in a number of preclinical models of psychiatric disorders and highlights the histaminergic system as a potential therapeutic target for the treatment of anxiety-related and depression-related disorders.
先前的研究表明组胺H₃受体（H₃R）信号传导与抗焦虑样和抗抑郁样作用之间可能存在联系。本研究的目的是研究新型H₃R拮抗剂ST - 1283与地西泮和氟西汀相比，对焦虑相关行为和抑郁相关行为的急性影响。在雄性C57BL / 6小鼠中，使用高架十字迷宫试验、旷场试验、埋珠试验、悬尾试验、新奇抑制摄食试验和强迫游泳试验评估ST - 1283的作用。结果表明，与地西泮一样，ST - 1283（7.5毫克/千克）显著改变了高架十字迷宫试验中观察到的所有参数。此外，在旷场试验中，ST - 1283显著增加了在场地中心停留的时间，而没有改变一般运动活动。同样，在埋珠试验中，ST - 1283减少了埋珠的数量以及挖掘时间。悬尾试验和强迫游泳试验表明，ST - 1283能够减少不动时间，与公认的抗抑郁药氟西汀一样。在新奇抑制摄食试验中，用ST - 1283治疗可缩短摄食潜伏期，而对笼内食物摄入量没有影响。重要的是，用H₃R激动剂R-α-甲基组胺预处理可消除ST - 1283的抗焦虑和抗抑郁作用。综上所述，本系列研究证明了这种新合成的H₃R拮抗剂在许多精神疾病临床前模型中的新作用，并突出了组胺能系统作为治疗焦虑相关和抑郁相关疾病的潜在治疗靶点。
