Poncelet M, Perio A, Simiand J, Gout G, Soubrie P, Le Fur G
Sanofi Recherche, Montpellier, France.
J Neural Transm Gen Sect. 1995;102(2):83-90. doi: 10.1007/BF01276504.
We have investigated the effect of SR 57227A, a selective 5-HT3 receptor agonist which crosses the blood brain barrier, on three rodent models in which antidepressants are active. In the forced swimming test, SR 57227A dose-dependently reduced the duration of immobility in mice and rats after i.p. administration. (ED50 = 14.2 mg/kg i.p. in mice, and 7.6 mg/kg i.p. in rats.) The compound was also active in both species after oral administration. In a time-course study in mice, SR 57227A (20 mg/kg p.o.) produced a significant effect lasting 6 h. SR 57227A (1 and 3 mg/kg i.p.) reduced the elevation of the escape failures in the learned helplessness model in rats by 50-60% on the last two days of the avoidance task, and reduced isolation-induced aggressivity in mice by 50 to 85%, an effect which was antagonised by zacopride (1 mg/kg i.p.). These results suggest that the stimulation of 5-HT3 receptors can produce antidepressant-like effects in behavioral tests in rodents.
我们研究了可穿越血脑屏障的选择性5-羟色胺3（5-HT3）受体激动剂SR 57227A对三种抗抑郁药有效的啮齿动物模型的作用。在强迫游泳试验中，腹腔注射给药后，SR 57227A能剂量依赖性地缩短小鼠和大鼠的不动时间。（小鼠腹腔注射的半数有效剂量[ED50]为14.2毫克/千克，大鼠腹腔注射的ED50为7.6毫克/千克。）口服给药后，该化合物在这两个物种中也具有活性。在一项针对小鼠的时间进程研究中，SR 57227A（口服20毫克/千克）产生了持续6小时的显著效果。SR 57227A（腹腔注射1和3毫克/千克）在逃避任务的最后两天，使大鼠习得性无助模型中的逃避失败次数增加减少了50%至60%，并使小鼠隔离诱导的攻击性降低了50%至85%，扎考必利（腹腔注射1毫克/千克）可拮抗这一作用。这些结果表明，在啮齿动物的行为测试中，刺激5-HT3受体可产生抗抑郁样效应。
