1. Academic Validation
  2. SMIP004: A compound with antidepressant-like activities in mouse models

SMIP004: A compound with antidepressant-like activities in mouse models

  • Eur J Pharmacol. 2019 Jan 15;843:260-267. doi: 10.1016/j.ejphar.2018.11.039.
Dan Wang 1 Xing Xu 1 Yue Wu 1 Yong Lin 1 Minhui Gao 1 Peili Hu 1 Dongjian Chen 2 Xu Lu 1 Zhuo Chen 2 Hui Wang 3 Chao Huang 4
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong, Jiangsu 226001, China.
  • 2 Invasive Technology Department, Nantong First People's Hospital, The Second Affiliated Hospital of Nantong University, #6 North Road Hai'er Xiang, Nantong, Jiangsu 226001, China.
  • 3 Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong, Jiangsu 226001, China. Electronic address: wangh4@rwjms.rugers.edu.
  • 4 Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong, Jiangsu 226001, China. Electronic address: huachao@ntu.edu.cn.
Abstract

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.

Keywords

Chronic unpredictable stress; Depression; Fluoxetine; S-phase kinase-associated protein 2; SMIP004.

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