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Indian Journal of Pharmaceutical Education and ResearchNOW IN
Article

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

Xiaohui Wang1, Yajing Li2, Yinxue Shen3, Dongzi Zhang4★★ Corresponding author

  1. 1Wenzhou Medical University, Major in Clinical Medicine, Wenzhou, Zhejiang, CHINA.
  2. 2Department of General, Community Health Service Center (District Hospital), Baoding, Hebei, CHINA.
  3. 3School of Applied Psychology, North China University of Technology, Tangshan, Hebei, CHINA.
  4. 4Psychological Counseling Clinic, Affiliated Hospital of Hebei University, Baoding, Hebei, CHINA.

CORRESPONDENCE

Dongzi Zhang

Psychological Counseling Clinic, Affiliated Hospital of Hebei University, Baoding, Hebei, CHINA.

zhangdongzi6688@sina.com

Received: 04-01-2020; Revised: 27-04-2020; Accepted: 19-05-2020.

Volume 54, Issue 3 · pp. 682–689 · PUBLISHED 2020 · DOI: 10.5530/ijper.54.3.118

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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.

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    Wang, X., Li, Y., Shen, Y., & Zhang, D. (2020). Exploring the Role and Mechanism of Imatinib in Chronic Unpredictable Mild Stress-induced Depression Model of Rats. Indian Journal of Pharmaceutical Education and Research, 54(3), 682–689. https://doi.org/10.5530/ijper.54.3.118