ANTIDEPRESSANT ACTIVITY OF NONCOMPETITIVE AND COMPETITIVE NMDA RECEPTOR ANTAGONISTS IN A CHRONIC MILD STRESS MODEL OF DEPRESSION
ANTIDEPRESSANT ACTIVITY OF NONCOMPETITIVE AND COMPETITIVE NMDA RECEPTOR ANTAGONISTS IN A CHRONIC MILD STRESS MODEL OF DEPRESSION
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DOI：
10.1016/0014-2999(94)90516-9
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发表时间：
1994-09-22
影响因子：
5
通讯作者：
MORYL, E
中科院分区：
文献类型：
--
作者：
PAPP, M;MORYL, E
在慢性轻度应激抑郁模型中，研究了非竞争性NMDA受体拮抗剂MK-801（地佐环平）和竞争性NMDA受体拮抗剂CGP 37849（DL-（E）-2-氨基-4-甲基-5-膦酰基-3-戊酮酸）及其（R）-对映体CGP 40116的抗抑郁特性。在该模型中，动物经受各种轻度应激源持续延长的时间段，显示出可口蔗糖溶液的消耗量显著降低（快感缺乏）。先前已证明，慢性轻度应激诱导的快感缺失可通过各种抗抑郁药物的慢性治疗来逆转。在本研究中，我们发现MK-801（0.3 mg/kg i. p.）长期（4-5周）给药可逐渐逆转应激诱导的蔗糖摄入不足，CGP 37849（5 mg/kg i.p.）和CGP（25 mg/kg p.o.）。该效应的大小及其时间过程与丙咪嗪类似给药（10 mg/kg i. p.或p.o.）后观察到的结果相当。长期给予丙咪嗪和NMDA受体拮抗剂后蔗糖摄入量的增加是特定于应激动物的;非应激对照组的行为不受任何测试药物的影响。这些结果证实了以前在“正常”动物上进行的研究，表明NMDA受体拮抗剂可能具有抗抑郁特性。
The antidepressant properties of the non-competitive NMDA receptor antagonist, MK-801 (dizocilpine), and the competitive NMDA receptor antagonist, CGP 37849 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentonoic acid) and its (R)-enantiomer CGP 40116, were studied in a chronic mild stress model of depression. In this model animals subjected to a variety of mild stressors for a prolonged period of time show a substantial decrease in the consumption of palatable sucrose solution (anhedonia). It was previously demonstrated that the chronic mild stress-induced anhedonia can be reversed by chronic treatment with various antidepressant drugs. In this study we found that the stress-induced deficit in sucrose intake was gradually reversed by chronic (4-5 weeks) treatment with MK-801 (0.3 mg/kg i.p.), CGP 37849 (5 mg/kg i.p.) and CGP (25 mg/kg p.o.). The magnitude of this effect and its time course were comparable to those observed following similar administration of imipramine (10 mg/kg i.p. or p.o.). The increase in sucrose intake following chronic administration of imipramine and NMDA receptor antagonists was specific to stressed animals; the behaviour of non-stressed controls was unchanged by any of the drugs tested. These results confirm those of previous studies, carried out on 'normal' animals, suggesting that antagonists of NMDA receptors may have antidepressant properties.