Exploring the anti-stress effects of imatinib and tetrabenazine in cold-water immersion-induced acute stress in mice
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ORIGINAL ARTICLE
Exploring the anti-stress effects of imatinib and tetrabenazine in cold-water immersion-induced acute stress in mice Manish Kumar 1 & Nirmal Singh 1 & Amteshwar Singh Jaggi 1 Received: 4 December 2019 / Accepted: 24 March 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Imatinib . Tetrabenazine . Acute stress . Behavioural changes . Corticosterone
Introduction Stress is defined as the non-specific response of the body to any demand (Selye, 1998). It is the state of threatened homeostasis that disturbs the normal physiological equilibrium of body and endangers the survival of an individual (Joseph & Whirledge, 2017). An acute as well as chronic exposure to a given stress stimulus induces changes in the behaviour, hypothalamic-pituitary-adrenal axis (HPA-axis) and autonomic functions (Tsigos & Chrousos, 2002). Stress response is mainly influenced by the duration and intensity of different stressors (Armario et al., 1990). Acute stress has also been reported to play a vital role in the development of various brain diseases and their related symptoms including Parkinson’s disease (Mitsumoto & Mori, 2018), hyperthermia (Miyamoto et al., 2017), depression (Mancuso et al., 2010)
* Amteshwar Singh Jaggi [email protected] 1
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India
and neuroinflamation (Munhoz et al., 2008). Apart from the role of stress in the pathogenesis of brain disorders, it has also been documented as a risk factor for the induction of cardiovascular diseases (Lagraauw et al., 2
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