Exploring the anti-stress effects of imatinib and tetrabenazine in cold-water immersion-induced acute stress in mice

Abstract

The aim of the present study was to explore the ameliorative role of imatinib and tetrabenazine in acute stress–induced behavioural and biochemical changes in mice. Cold-water immersion (5 min duration) was employed to induce acute stress and the resulting changes in the locomotor activity, exploratory behaviour, motor activity and social behaviour were assessed using the actophotometer, the hole board, the open field and the social interaction tests. The biochemical alterations were assessed by measuring the plasma corticosterone levels using ELISA kit. Cold-water immersion-induced acute stress diminished the locomotor activity, exploratory behaviour, motor activity and social behaviour along with increase in the plasma corticosterone levels. Administration of imatinib (50 and 100 mg/kg, i.p.), a tyrosine kinase inhibitor, significantly attenuated the cold-water immersion-induced behavioural alterations with normalization of the plasma corticosterone levels in a dose-dependent manner. Moreover, administration of tetrabenazine (1 and 2 mg/kg, i.p.), a vesicular monoamine transporter 2 (VMAT2) inhibitor, also abolished the acute stress–induced behavioural and biochemical changes in a dose-dependent manner. The beneficial effects of imatinib and tetrabenazine in normalizing acute stress–induced biochemical and behavioural changes make them promising therapeutic agents in the treatment of acute stress–related problems.

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Acknowledgements

The authors are thankful to the Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India for providing facilities for this research work. The authors are grateful to Laurus Labs Limited, Visakhapatnam, Andhra Pradesh, India, for giving us the gift sample of imatinib for this work. The authors are also grateful to Inke, S.A., Barcelona, Spain, for providing us the gift sample of tetrabenazine for this work.

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MK contributed in the experimental work related to the study and drafted the manuscript. NS contributed in designing the study and critically revised the manuscript. ASJ contributed in designing the study, gave guidance related to the experimental work, revised the manuscript carefully and gave final approval.

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Correspondence to Amteshwar Singh Jaggi.

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Kumar, M., Singh, N. & Jaggi, A.S. Exploring the anti-stress effects of imatinib and tetrabenazine in cold-water immersion-induced acute stress in mice. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1625–1634 (2020). https://doi.org/10.1007/s00210-020-01862-w

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Keywords

  • Imatinib
  • Tetrabenazine
  • Acute stress
  • Behavioural changes
  • Corticosterone