School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
J Complement Integr Med. 2021 Sep 16;19(3):581-589. doi: 10.1515/jcim-2021-0159. eCollection 2022 Sep 1.
The effects of intra-ventral hippocampal memantine administration in male NMRI stressed mice were studied.
Two stainless steel gauge 23 guide cannulas were placed in the middle part of the mice ventral hippocampus using stereotaxic coordination. Seven days later, the animals were undergone to the stress protocol as follows: They experience four consecutive electro-foot shock stress sessions lasting for 10 min. Five or 30 min before each stress session, the animals received intra-ventral hippocampal (0.1, 1 and, 5 µg/mouse) or intraperitoneal (1, 5, and 10 mg/kg) memantine respectively. Eight days after stress termination, the animals were tested either for the maintenance of either anxiety (elevated plus maze) or depression (forced swimming test).
Animals show anxiety eight days after stress termination. Intra-ventral hippocampal infusion of memantine (5 µg/mouse) 5 min before stress inhibited the anxiety-like behaviors. However, other doses of the drug exacerbate the stress effect. The drug, when injected peripherally exacerbated the stress effect in all doses. The drug by itself had no effect. In addition, animals also show depression nine days after stress termination and memantine (0.1, 1, and 5 µg/mouse) reduced the stress effect. The drug (0.1 µg/mouse) by itself induced depression in the animals. However, the drug when injected peripherally reduced the stress effect in all doses.
It could be concluded that NMDA glutamate receptors in the ventral hippocampus may play a pivotal role in the mediation of maintenance of anxiety and depression induced by stress in the mice.
研究内侧海马给予美金刚对雄性 NMRI 应激小鼠的影响。
使用立体定位协调将两根不锈钢 23 号测量规引导管放置在小鼠海马中部。7 天后，动物进行应激程序如下：它们经历连续 4 次 10 分钟的电足电击应激。在每次应激前 5 或 30 分钟，动物分别接受内侧海马（0.1、1 和 5μg/只）或腹腔内（1、5 和 10mg/kg）美金刚。应激结束 8 天后，动物进行焦虑（高架十字迷宫）或抑郁（强迫游泳试验）的维持测试。
动物在应激结束 8 天后表现出焦虑。应激前 5 分钟内侧海马内注射美金刚（5μg/只）可抑制类焦虑行为。然而，其他剂量的药物则加剧了应激的影响。药物本身无作用。此外，动物在应激结束 9 天后也表现出抑郁，美金刚（0.1、1 和 5μg/只）减轻了应激的影响。药物（0.1μg/只）本身会导致动物抑郁。然而，药物经腹腔注射时在所有剂量下均减轻了应激的影响。
可以得出结论，内侧海马的 NMDA 谷氨酸受体可能在介导应激诱导的焦虑和抑郁的维持中发挥关键作用。
