Martin P, Soubrié P, Puech A J
Département de Pharmacologie, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Psychopharmacology (Berl). 1990;101(3):403-7. doi: 10.1007/BF02244061.
Serotonergic systems are thought to be involved in the mechanisms of action of antidepressants in humans. There is little evidence, however, to suggest that serotonin uptake blockers are efficacious in animal models of depression. To further explore the antidepressant activity of these drugs, four compounds from this class (citalopram, fluvoxamine, indalpine or zimelidine) were tested in rats subjected to helplessness training. Rats were first exposed to inescapable shocks and 48 h later, shuttle-box training was initiated to evaluate escape learning. Twice-daily IP injections of citalopram (1 mg/kg), fluvoxamine (4 mg/kg), indalpine (1 and 2 mg/kg) and zimelidine (1 and 2 mg/kg) reduced escape deficits in a manner similar to that produced by the tricyclic antidepressants desipramine and clomipramine. Reversal of escape deficit by serotonin uptake blockers was observed only when the drugs were administered after the shuttlebox sessions. At higher doses, the four serotonin uptake blockers were without effect. These data suggest that serotonin uptake blockers exert antidepressant-like effects in animals but only when they produce a moderate stimulation of serotonin neurotransmission.
血清素能系统被认为参与了抗抑郁药在人体中的作用机制。然而，几乎没有证据表明血清素摄取阻滞剂在动物抑郁模型中有效。为了进一步探索这些药物的抗抑郁活性，对该类中的四种化合物（西酞普兰、氟伏沙明、茚达品或齐美利定）在接受无助训练的大鼠中进行了测试。大鼠首先暴露于不可逃避的电击下，48小时后开始穿梭箱训练以评估逃避学习。每天两次腹腔注射西酞普兰（1毫克/千克）、氟伏沙明（4毫克/千克）、茚达品（1和2毫克/千克）和齐美利定（1和2毫克/千克），其减轻逃避缺陷的方式与三环类抗抑郁药地昔帕明和氯米帕明相似。仅当在穿梭箱训练后给药时，才观察到血清素摄取阻滞剂对逃避缺陷的逆转作用。在较高剂量时，这四种血清素摄取阻滞剂没有效果。这些数据表明，血清素摄取阻滞剂在动物中发挥类似抗抑郁的作用，但仅当它们对血清素神经传递产生适度刺激时才起作用。
