Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box, 13145-784 Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Eur J Pharmacol. 2014 Jul 15;735:26-31. doi: 10.1016/j.ejphar.2014.03.053. Epub 2014 Apr 13.
Opioid and glutamatergic receptors have a key role in depression following stress. In this study, we assessed opioid and glutamatergic receptors interaction with the depressant-like behavior of acute foot-shock stress in the mouse forced swimming test. Stress was induced by intermittent foot shock stimulation during 30min and swim periods were afterwards conducted by placing mice in separated glass cylinders filled with water for 6min. The immobility time during the last 4min of the test was considered. Acute foot-shock stress significantly increased the immobility time of mice compared to non-stressed control group (P≤0.01). Administration of non-selective opioid receptors antagonist, naltrexone (1 and 2mg/kg, i.p.), and the selective non-competitive NMDA receptor antagonist, MK-801 (0.05mg/kg, i.p.), and the selective serotonin reuptake inhibitor, fluoxetine (5mg/kg), significantly reduced the immobility time in stressed animals (P≤0.01). Lower doses of MK-801 (0.01mg/kg), naltrexone (0.3mg/kg), NMDA (75mg/kg) and morphine(5mg/kg) had no effect on foot-shock stressed mice. Combined treatment of sub-effective doses of naltrexone and MK-801 significantly showed an antidepressant-like effect (P≤0.001). On the other hand, co-administration of non-effective doses of NMDA and morphine with effective doses of naltrexone and MK-801 reversed the anti-immobility effect of these drugs. Taken together, we have for the first time demonstrated the possible role of opioid/NMDA receptors signaling in the depressant-like effect of foot-shock stress, and proposed the use of drugs that act like standard anti-depressants in stress-induced depression.
阿片类和谷氨酸能受体在应激后抑郁中起关键作用。在这项研究中，我们评估了阿片类和谷氨酸能受体与小鼠强迫游泳试验中急性足底电击应激致抑郁样行为的相互作用。应激通过 30 分钟的间歇性足底电击刺激诱导，然后将小鼠放入单独的玻璃圆柱形容器中，在其中装满水进行 6 分钟游泳。测试的最后 4 分钟内记录不动时间。与非应激对照组相比，急性足底电击应激显著增加了小鼠的不动时间（P≤0.01）。非选择性阿片受体拮抗剂纳曲酮（1 和 2mg/kg，ip）和选择性非竞争性 NMDA 受体拮抗剂 MK-801（0.05mg/kg，ip）和选择性 5-羟色胺再摄取抑制剂氟西汀（5mg/kg）的给药显著减少了应激动物的不动时间（P≤0.01）。较低剂量的 MK-801（0.01mg/kg）、纳曲酮（0.3mg/kg）、NMDA（75mg/kg）和吗啡（5mg/kg）对足底电击应激的小鼠没有影响。纳曲酮和 MK-801 的亚有效剂量联合治疗显著表现出抗抑郁样作用（P≤0.001）。另一方面，纳曲酮和 MK-801 的有效剂量与 NMDA 和吗啡的非有效剂量共同给药逆转了这些药物的抗不动作用。总之，我们首次证明了阿片类/NMDA 受体信号在足底电击应激致抑郁样效应中的可能作用，并提出了使用类似标准抗抑郁药的药物治疗应激诱导的抑郁。
