SMIP004: A compound with antidepressant-like activities in mouse models
SMIP004: A compound with antidepressant-like activities in mouse models
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SMIP004：一种在小鼠模型中具有抗抑郁样活性的化合物
DOI：
10.1016/j.ejphar.2018.11.039
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Chao Huang
中科院分区：
文献类型：
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作者：
Dan Wang;Xing Xu;Yue Wu;Yong Ling;Minhui Gao;Peili Hu;Dongjian Chen;Xu Lu;Zhuo Chen;Hui Wang;Chao Huang
本研究旨在检查SMIP 004（S期激酶相关蛋白2（Skp 2）抑制剂）在C57 BL 6/J小鼠急性或慢性给药后在小鼠模型中发挥抗抑郁药样特性的效力。为此，利用悬尾试验（TST）、强迫游泳试验（FST）和蔗糖偏好试验（SPT），并在有或没有慢性不可预测的应激（CUS）处理的小鼠中评价SMIP 004在不同浓度或时间点的抗抑郁样活性。结果表明，在时间和剂量依赖性实验中，SMIP 004在未处理小鼠中的抗抑郁样活性发生在第11天，剂量为2和4 mg/kg。SMIP 004（2 mg/kg）在24小时给药方案中（试验前24、5和1小时）给药3次后，在未处理小鼠中也产生抗抑郁样活性，但在急性给药后（试验前1小时）则没有。在TST和FST中，发现SMIP 004-氟西汀联合给药可在未处理小鼠中诱导协同抗抑郁样作用。这些结果似乎是特异性的，因为不同实验组中的小鼠在旷场测试中没有显示出运动活动增加。此外，以2 mg/kg但不是1 mg/kg的剂量长期SMIP 004处理逆转了TST和FST中的不动时间的增加以及SPT中的蔗糖偏好的减少，这表明SMIP 004可以在应激条件下产生抗抑郁样活性。这些结果表明，SMIP 004在所有实验中都表现出明显的抗抑郁样活性，提示SMIP 004可能是一种新型的抗抑郁药。
This study was designed to examine the potency of SMIP004, an inhibitor of S-phase kinase-associated protein 2 (Skp2), to exert antidepressant-like properties in mouse models following acute or chronic administration to C57BL6/J mice. To this end, the tail suspension test (TST), forced swim test (FST), and sucrose preference test (SPT) were utilized and the antidepressant-like activity of SMIP004 at different concentrations or time points in mice with or without chronic unpredictable stress (CUS) treatment were evaluated. Results showed that in the time- and dose-dependent experiment the antidepressant-like activity of SMIP004 in naïve mice occurred at day 11 and at the dosage of 2 and 4 mg/kg. SMIP004 (2 mg/kg) also produces antidepressant-like activities in naïve mice after three times in a 24-h administration scheme (24, 5, and 1 h before the test) but not after acute treatment (1 h before the test). Combined SMIP004-fluoxetine administration was found to induce coordinated antidepressant-like effects in naïve mice in the TST and FST. These results seem to be specific because the mice in different experimental groups showed no increased locomotor activity in the open field test. Further, long-term SMIP004 treatment at the dosage of 2 but not 1 mg/kg reversed CUS-induced increase in immobility time in the TST and FST as well as CUS-induced decrease in sucrose preference in the SPT, suggesting that SMIP004 can produce antidepressant-like activities at stressed conditions. These results show that SMIP004 displays obvious antidepressant-like activities in all conducted tests, and suggest that SMIP004 might be a novel antidepressant.