Exploring the Role and Mechanism of Imatinib in Chronic Unpredictable Mild Stress-induced Depression Model of Rats

Indian Journal of Pharmaceutical Education and Research

  • Xiaohui Wang1Wenzhou Medical University, Major in Clinical Medicine, Wenzhou, Zhejiang, CHINA.
  • Yajing Li2Department of General, Community Health Service Center (District Hospital), Baoding, Hebei, CHINA.
  • Yinxue Shen3School of Applied Psychology, North China University of Technology, Tangshan, Hebei, CHINA.
  • Dongzi Zhang4Psychological Counseling Clinic, Affiliated Hospital of Hebei University, Baoding, Hebei, CHINA.

Volume 54 Issue 3 Pages 682-689

DOI: 10.5530/ijper.54.3.118

Abstract

Aim: The study was planned to examine the potential effect of imatinib in chronic unpredictable mild stress (CUMS)-induced depression model of rats. Materials and Methods: Male rats were subjected to the 6-week CUMS with unpredictable stressors to induce depression and the imatinib was started from the 4th week (for 21 days during 6 weeks of the protocol). Results: CUMS significantly increased immobility time and decreased consumption of sucrose in the swimming and sucrose preference test respectively. Furthermore, a considerable reduction in the Brain-derived neurotrophic factor (BDNF) levels and an increase in phosphorylated NF-kB levels (p-NF-kB) were noticed in the prefrontal cortex (PFC). However, imatinib (25 and 50 mg/kg) significantly reversed sucrose consumption as well as reduced immobility times in CUMS-subjected rats, suggesting the antidepressant potential of imatinib. Moreover, imatinib treatment significantly increases in the levels of BDNF and a decrease in the p-NF-kB levels in the PFC of the brain of stress-subjected rats. The co-administration of tropomyosin receptor kinase B (TrkB) antagonist, ANA-12 (0.25 and 0.5 mg/kg) with imatinib (50 mg/kg) considerably attenuated imatinib-mediated antidepressant effects in sucrose preference behavior and immobility period in CUMS subjected rats. ANA-12 abolished imatinibinduced effects in stress-subjected rats. Conclusion: The antidepressant actions of imatinib may be attributed to an increase in the BDNF levels and a decrease in the p-NFkB levels in the stress-susceptible PFC region of the CUMS subjected rats.

Keywords

  • CUMS
  • Depression
  • p-NF-kB
  • BDNF
  • Imatinib
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