首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Behavioral effects of saredutant, a tachykinin NK2 receptor antagonist, in experimental models of mood disorders under basal and stress-related conditions.
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Behavioral effects of saredutant, a tachykinin NK2 receptor antagonist, in experimental models of mood disorders under basal and stress-related conditions.

机译:速激肽NK2受体拮抗剂saredutant在基础和压力相关条件下的情绪障碍实验模型中的行为效应。

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摘要

The present study was made to investigate the role of tachykinin NK2 receptors in the expression of stress-related behaviors in animals. Under basal conditions, intraperitoneal (i.p.) administration of the selective tachykinin NK2 receptor antagonist, saredutant (1 and 3 mg/kg) or diazepam (1 mg/kg) exerted anxiolytic-like effects in rodents, as they reduced grooming score of Wistar male rats tested in the novelty-induced grooming sampling test (NGT) and increased percentage of time and entries in open arms of Swiss male mice tested in the elevated plus maze (EPM) test. After previous exposure to stress-related conditions, as induced by a 2-min forced swim made 5 min prior to the EPM test, saredutant but not diazepam, exhibited anxiolytic-like effects in mice. To study the antidepressant-like activity of tachykinin NK2 receptor antagonist under basal conditions, different groups of rats were injected i.p. with saredutant (2.5, 5 and 10 mg/kg) or the tricyclic antidepressant, clomipramine (50 mg/kg) andtested in the forced swim test (FST), a widely used antidepressant-responsive test. The influence of stress-related conditions was studied in rats subjected to electric foot-shocks (1 mA, 1 s) 24, 5 and 1 h prior to FST, after drugs injection. In the FST, clomipramine decreased the immobility time only under basal conditions, but not after application of acute foot-shocks. To the contrary, saredutant-treated rats also exhibited more active behavior in FST after previous exposure to stressors. These results give further support to the hypothesis that tachykinin NK2 receptors may be a therapeutic target for pharmacological treatment of stress-related diseases, such as anxiety and depression.
机译:本研究旨在研究速激肽NK2受体在动物应激相关行为表达中的作用。在基础条件下,腹膜内(ip)施用选择性速激肽NK2受体拮抗剂,鼠尾草(1和3 mg / kg)或地西epa(1 mg / kg)在啮齿动物中表现出抗焦虑样作用,因为它们降低了Wistar雄性的修饰得分在新颖性诱导美容取样测试(NGT)中测试的雌性大鼠,在高架迷宫(EPM)测试中测试的瑞士雄性小鼠张开双臂的时间和进入百分比增加。在先前暴露于与压力相关的条件下(如在EPM测试前5分钟进行的2分钟强迫游泳所引起的),芥兰而不是地西epa在小鼠中表现出抗焦虑作用。为了研究速激肽NK2受体拮抗剂在基础条件下的抗抑郁样活性,对不同组的大鼠进行了腹腔注射。含有芥末(2.5、5和10 mg / kg)或三环抗抑郁药氯米帕明(50 mg / kg),并在广泛使用的抗抑郁药反应性试验(FST)中进行了测试。在药物注射后24、5和1小时,在FST前,电击脚(1 mA,1 s)的大鼠中研究了应激相关条件的影响。在FST中,氯米帕明只能在基础条件下减少不动时间,而在应用急性足部冲击后则不会减少。相反,在先前暴露于应激源后,使用药敏的大鼠在FST中也表现出更活跃的行为。这些结果进一步支持了速激肽NK2受体可能是应激相关疾病(如焦虑症和抑郁症)药理治疗的治疗靶点的假设。

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