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选择性5-羟色胺7受体拮抗剂SB 269970在焦虑和抑郁动物模型中的作用

Effect of the selective 5-HT7 receptor antagonist SB 269970 in animal models of anxiety and depression.

作者信息

Wesołowska Anna, Nikiforuk Agnieszka, Stachowicz Katarzyna, Tatarczyńska Ewa

机构信息

Department of New Drugs Research, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Kraków PL 31-343, Poland.

出版信息

Neuropharmacology. 2006 Sep;51(3):578-86. doi: 10.1016/j.neuropharm.2006.04.017. Epub 2006 Jul 7.

Abstract

The aim of the present study was to examine the effect of the selective 5-HT7 receptor antagonist SB 269970 (0.25-20 mg/kg) in the behavioral tests commonly used for predicting anxiolytic- and antidepressant-like activity. Diazepam and imipramine were used as standard drugs. SB 269970 (in one medium dose of 0.5 or 1 mg/kg) exerted a specific antianxiety-like effect in the Vogel drinking test in rats, in the elevated plus-maze test in rats and in the four-plate test in mice. Moreover, SB 269970 (in one medium dose of 5 or 10 mg/kg) showed antidepressant-like activity in the forced swimming and the tail suspension tests in mice. At the same time, the tested compound at doses of 1-20 mg/kg did not change the spontaneous locomotor activity of mice. The potential anxiolytic and antidepressant effects produced by SB 269970 were weaker than those of the reference drugs employed. It is noteworthy that the active doses of SB 269970 were devoid of any visible motor side-effects. In conclusion, the results of our studies indicate that 5-HT7 receptor antagonists may play a role in the therapy of both anxiety and depression.

摘要

本研究的目的是在常用于预测抗焦虑和抗抑郁样活性的行为测试中,考察选择性5-HT7受体拮抗剂SB 269970(0.25 - 20 mg/kg)的作用。地西泮和丙咪嗪用作标准药物。SB 269970(中等剂量为0.5或1 mg/kg)在大鼠的Vogel饮水试验、大鼠高架十字迷宫试验和小鼠四板试验中发挥了特异性抗焦虑样作用。此外,SB 269970(中等剂量为5或10 mg/kg)在小鼠强迫游泳试验和悬尾试验中表现出抗抑郁样活性。同时,1 - 20 mg/kg剂量的受试化合物未改变小鼠的自发运动活性。SB 269970产生的潜在抗焦虑和抗抑郁作用比所用参比药物的作用弱。值得注意的是,SB 269970的有效剂量没有任何明显的运动副作用。总之,我们的研究结果表明,5-HT7受体拮抗剂可能在焦虑症和抑郁症的治疗中发挥作用。

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