Effects of sigma ligands on NMDA receptor function in the bulbectomy model of depression: a behavioural study in the rat
Effects of sigma ligands on NMDA receptor function in the bulbectomy model of depression: a behavioural study in the rat
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DOI：
10.1017/s1461145701002760
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发表时间：
2002-03-01
影响因子：
4.8
通讯作者：
Debonnel, G
中科院分区：
文献类型：
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作者：
Bermack, J;Lavoie, N;Debonnel, G
西格玛(Sigma)配体已被证明可以调节NMDA受体的活性。在本研究中，我们使用嗅球切开术(OBX)抑郁症动物模型来评估西格玛(1)配体伊格美辛对OBX诱导的行为的影响。行为学实验表明，与假手术大鼠(生理盐水处理)相比，OBX(生理盐水处理)大鼠增加了地佐西平诱导的行为改变，包括运动和转圈活动。短期(7d)服用小剂量异美辛(50-200 mg/kg)。(D.S.C.)对地佐西平诱导的行为没有影响，而长期(14d)给予小剂量异美辛逆转了去球部的作用，使处理的013X大鼠的行为与假生理盐水大鼠没有显着差异。短期服用大剂量异美辛(500-1000 mg/kg。D)也逆转了OBX大鼠(生理盐水处理)增加的运动和转圈行为，而同样高剂量的长期治疗不会。这些结果为Sigma配体逆转OBX诱导的一些行为提供了行为证据。此外，他们支持先前报道的配体的钟形剂量-反应曲线的概念。
Sigma (sigma) ligands have been shown to modulate NMDA receptor activity. In the present study we used the olfactory bulbectomy (OBX) animal model of depression to assess the effects of the sigma(1) ligand igmesine on OBX-induced behaviour. Behavioural experiments demonstrated OBX (saline-treated) rats to have increased dizocilpine-induced behavioural modifications, including locomotor and circling activity as compared to Sham rats (saline-treated). A short-term (7 d) treatment with low doses of igmesine (50-200 mug/kg. d s.c.) had no effect on dizocilpine-induced behaviour while long-term treatments (14 d) with low doses of igmesine reversed the effect of the bulbectomy such that the treated 013X rats' behaviour was not significantly different from Sham-saline rats. Short-term treatments with high doses of igmesine (500-1000 mug/kg. d) also reversed the increased locomotor and circling behaviour seen in OBX rats (saline-treated) while long-term treatments with the same high doses did not. These results provide behavioural evidence for sigma ligand's potential to reverse some OBX-induced behaviours. Moreover, they support the notion of a bell-shaped dose-response curve previously reported for a ligands.