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

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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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References

  • Selye H (1998) A syndrome produced by diverse nocuous agents. J Neuropsychiatr Clin Neurosci 10(2):230–231

    CAS  Google Scholar 

  • Joseph DN, Whirledge S (2017 Oct 24) Stress and the HPA Axis: balancing homeostasis and fertility. Int J Mol Sci 18(10):E2224

    PubMed  Google Scholar 

  • Tsigos C, Chrousos GP (2002) Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res 53(4):865–871

    PubMed  Google Scholar 

  • Armario A, Marti J, Gil M (1990) The serum glucose response to acute stress is sensitive to the intensity of the stressor and to habituation. Psychoneuroendocrinology. 15:341–347

    CAS  PubMed  Google Scholar 

  • Mitsumoto Y, Mori A (2018) Acute restraint stress augments 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity via increased toxin uptake into the brain in C57BL/6 mice. Neurosci Bull 34(5):849–853

    CAS  PubMed  PubMed Central  Google Scholar 

  • Miyamoto T, Funakami Y, Kawashita E, Nomura A, Sugimoto N, Saeki H, Tsubota M, Ichida S, Kawabata A (2017) Repeated cold stress enhances the acute restraint stress-induced hyperthermia in mice. Biol Pharm Bull 40(1):11–16

    CAS  PubMed  Google Scholar 

  • Mancuso C, Navarra P, Preziosi P (2010) Roles of nitric oxide, carbon monoxide, and hydrogen sulfide in the regulation of the hypothalamic-pituitary-adrenal axis. J Neurochem 113(3):563–575

    CAS  PubMed  Google Scholar 

  • Munhoz CD, Garcia-Bueno B, Madrigal JL, Lepsch LB, Scavone C, Leza JC (2008) Stress-induced neuroinflammation: mechanisms and new pharmacological targets. Braz J Med Biol Res 41(12):1037–1046

    CAS  PubMed  Google Scholar 

  • Lagraauw HM, Kuiper J, Bot I (2015) Acute and chronic psychological stress as risk factors for cardiovascular disease: insights gained from epidemiological, clinical and experimental studies. Brain Behav Immun 50:18–30

    PubMed  Google Scholar 

  • Zhang X, Yu M, Yu W, Weinberg J, Shapiro J, McElwee KJ (2009) Development of alopecia areata is associated with higher central and peripheral hypothalamic-pituitary-adrenal tone in the skin graft induced C3H/HeJ mouse model. J Invest Dermatol 129(6):1527–1538

    CAS  PubMed  Google Scholar 

  • Caso JR, Leza JC, Menchen L (2008) The effects of physical and psychological stress on the gastro-intestinal tract: lessons from animal models. Curr Mol Med 8(4):299–312

    CAS  PubMed  Google Scholar 

  • Steptoe A, Hamer M, Chida Y (2007) The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun 21(7):901–912

    CAS  PubMed  Google Scholar 

  • Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, Apperley J, Cervantes F, Cortes J, Deininger M, Gratwohl A, Guilhot F, Horowitz M, Hughes T, Kantarjian H, Larson R, Niederwieser D, Silver R, Hehlmann R (2006) European LeukemiaNet. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 108(6):1809–1820

    CAS  PubMed  Google Scholar 

  • Ben AE, Demetri GD (2016) A safety evaluation of imatinib mesylate in the treatment of gastrointestinal stromal tumor. Expert Opin Drug Saf 15(4):571–578

    Google Scholar 

  • Paul MK, Mukhopadhyay AK (2004) Tyrosine kinase-role and significance in cancer. Int J Med Sci 1(2):101–115

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hirano AA, Greengard P, Huganir RL (1988) Protein tyrosine kinase activity and its endogenous substrates in rat brain: a subcellular and regional survey. J Neurochem 50(5):1447–1455

    CAS  PubMed  PubMed Central  Google Scholar 

  • Savage DG, Antman KH (2002) Imatinib mesylate-a new oral targeted therapy. N Engl J Med 346(9):683–693

    CAS  PubMed  Google Scholar 

  • Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344(14):1031–1037

    CAS  PubMed  Google Scholar 

  • Wu R, Chen H, Ma J, He Q, Huang Q, Liu Q, Li M, Yuan Z (2016) c-Abl–p38α signaling plays an important role in MPTP-induced neuronal death. Cell Death Differ 23(3):542–552

    CAS  PubMed  Google Scholar 

  • Cancino GI, Perez AK, Castro PU, Toledo EM, von Bernhardi R, Alvarez AR (2011) c-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice. Neurobiol Aging 32(7):1249–1261

    CAS  PubMed  Google Scholar 

  • Kumar M, Kulshrestha R, Singh N, Jaggi AS (2019) Expanding spectrum of anticancer drug, imatinib, in the disorders affecting brain and spinal cord. Pharmacol Res 143:86–96

    CAS  PubMed  Google Scholar 

  • Sogawa R, Kimura S, Yakabe R, Mizokami Y, Tasaki M, Sueoka-Aragane N, Narisawa Y, Kimura S (2018) Anxiety and depression associated with tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia. Int J Clin Oncol 23:974–979

    CAS  PubMed  Google Scholar 

  • Boxall AR, Lancaster B, Garthwaite J (1996) Tyrosine kinase is required for long-term depression in the cerebellum. Neuron. 16:805–813

    CAS  PubMed  Google Scholar 

  • Kutlu MG, Cole RD, Connor DA, Natwora B, Gould TJ (2018) Tyrosine receptor kinase B receptor activation reverses the impairing effects of acute nicotine on contextual fear extinction. J Psychopharmacol 32:367–372

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kenney CJ, Hunter CB, Mejia NI, Jankovic J (2007) Tetrabenazine in the treatment of Tourette syndrome. J Pediatr Neurol 5(1):9–13

    CAS  Google Scholar 

  • Yero T, Rey JA (2008) Tetrabenazine (Xenazine), an FDA-approved treatment option for Huntington’s disease-related chorea. P T 33(12):690–694

    PubMed  PubMed Central  Google Scholar 

  • Harriott ND, Williams JP, Smith EB, Bozigian HP, Grigoriadis DE (2018) VMAT2 inhibitors and the path to ingrezza (Valbenazine). Prog Med Chem 57(1):87–111

    PubMed  Google Scholar 

  • Schafer MK, Weihe E, Eiden LE (2013) Localization and expression of VMAT2 across mammalian species: a translational guide for its visualization and targeting in health and disease. Adv Pharmacol 68:319–334

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eiden LE, Weihe E (2011) VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse. Ann N Y Acad Sci 1216:86–98

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tillinger A, Sollas A, Serova LI, Kvetnansky R, Sabban EL (2010) Vesicular monoamine transporters (VMATs) in adrenal chromaffin cells: stress-triggered induction of VMAT2 and expression in epinephrine synthesizing cells. Cell Mol Neurobiol 30(8):1459–1465

    CAS  PubMed  Google Scholar 

  • Kondo Y, To M, Saruta J, Hayashi T, Sugiyama H, Tsukinoki K (2013) Role of TrkB expression in rat adrenal gland during acute immobilization stress. J Neurochem 124:224–232

    CAS  PubMed  Google Scholar 

  • Zucker M, Aviv A, Shelef A, Weizman A, Rehavi M (2002) Elevated platelet vesicular monoamine transporter density in untreated patients diagnosed with major depression. Psychiatry Res 112:251–256

    CAS  PubMed  Google Scholar 

  • Kitanaka N, Kitanaka J, Hall FS, Kandori T, Murakami A, Muratani K, Nakano T, Uhl GR, Takemura M (2018) Tetrabenazine, a vesicular monoamine transporter-2 inhibitor, attenuates morphine-induced hyperlocomotion in mice through alteration of dopamine and 5-hydroxytryptamine turnover in the cerebral cortex. Pharmacol Biochem Behav 172:9–16

    CAS  PubMed  Google Scholar 

  • Lee KS, Lim BV, Jang MH, Shin MC, Lee TH, Kim YP, Shin HS, Cho SY, Kim H, Shin MS, Kim EH, Kim CJ (2002) Hypothermia inhibits cell proliferation and nitric oxide synthase expression in rats. Neurosci Lett 329(1):53–56

    CAS  PubMed  Google Scholar 

  • Agrawal A, Jaggi AS, Singh N (2011) Pharmacological investigations on adaptation in rats subjected to cold water immersion stress. Physiol Behav 103(3–4):321–329

    CAS  PubMed  Google Scholar 

  • Kee-Won K, Seong-Soo C, Ran-Sook W, Hong-Won S (2003) Development of anti-nociceptive tolerance and changes of opioid receptor ligand binding in central nervous system of the mouse forced to single and repeated swimming in the cold water. Brain Res Bull 61:93–97

    Google Scholar 

  • Kaur R, Jaggi AS, Singh N (2010) Studies on effect of stress preconditioning in restrain stress-induced behavioural alterations. Yakugaku Zasshi 130(2):215–221

    CAS  PubMed  Google Scholar 

  • Kumari B, Kumar A, Dhir A (2007) Protective effect of non-selective and selective COX-2-inhibitors in acute immobilization stress-induced behavioural and biochemical alterations. Pharmacol Rep 59:699–707

    CAS  PubMed  Google Scholar 

  • Brown GR, Nemes C (2008) The exploratory behaviour of rats in the hole-board apparatus: is head-dipping a valid measure of neophilia? Behav Process 78(3):442–448

    Google Scholar 

  • Takeda H, Tsuji M, Matsumiya T (1998) Changes in head-dipping behaviour in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol 350:21–29

    CAS  PubMed  Google Scholar 

  • Prut L, Belzung C (2003) The open field as a paradigm to measure the effects of drugs on anxiety-like behaviours: a review. Eur J Pharmacol 463(1–3):3–33

    CAS  PubMed  Google Scholar 

  • Roman E, Gustafsson L, Berg M, Nylander I (2006) Behavioural profiles and stress-induced corticosteroid secretion in male Wistar rats subjected to short and prolonged periods of maternal separation. Horm Behav 50(5):736–747

    CAS  PubMed  Google Scholar 

  • Verma M, Bali A, Singh N, Jaggi AS (2016) Investigating the role of nisoldipine in foot-shock-induced post-traumatic stress disorder in mice. Fundam Clin Pharmacol 30:128–136

    CAS  PubMed  Google Scholar 

  • Wilson CA, Koenig JI (2014) Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia. Eur Neuropsychopharmacol 24:759–773

    CAS  PubMed  Google Scholar 

  • Kaur A, Bali A, Singh N, Jaggi AS (2015) Investigating the stress attenuating potential of furosemide in immobilization and electric foot shock stress models in mice. Naunyn Schmiedeberg's Arch Pharmacol 388(5):497–507

    CAS  Google Scholar 

  • Manchanda RK, Jaggi AS, Singh N (2011) Ameliorative potential of sodium cromoglycate and diethyldithiocarbamic acid in restraint stress-induced behavioural alterations in rats. Pharmacol Rep 63(1):54–63

    CAS  PubMed  Google Scholar 

  • Jianhua F, Wei W, Xiaomei L, Shao-Hui W (2017) Chronic social defeat stress leads to changes of behaviour and memory-associated proteins of young mice. Behav Brain Res 316:136–144

    PubMed  Google Scholar 

  • Rodrigues MES, Bekhbat M, Houser MC, Chang J, Walker DI, Jones DP, do Oller Nascimento CMP, Barnum CJ, Tansey MG (2017) Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioural deficits in mice. Brain Behav Immun 59:158–172

    Google Scholar 

  • Browne CA, Hanke J, Rose C, Walsh I, Foley T, Clarke G, Schwegler H, Cryan JF, Yilmazer HD (2014) Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bi-directionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction. Stress. 17(6):471–483

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hwang KA, Hwang YJ, Hwang IG, Song J, Jun KY (2019) Low temperature-aged garlic extract suppresses psychological stress by modulation of stress hormones and oxidative stress response in brain. J Chin Med Assoc 82(3):191–195

    PubMed  Google Scholar 

  • Retana-Marquez S, Bonilla-Jaime H, Vazquez-Palacios G, Dominguez-Salazar E, Martinez-Garcia R, Velazquez-Moctezuma J (2003) Body weight gain and diurnal differences of corticosterone changes in response to acute and chronic stress in rats. Psychoneuroendocrinology. 28(2):207–227

    CAS  PubMed  Google Scholar 

  • Lafrance M, Roussy G, Belleville K, Maeno H, Beaudet N, Wada K, Sarret P (2010) Involvement of NTS2 receptors in stress-induced analgesia. Neuroscience. 166(2):639–652

    CAS  PubMed  Google Scholar 

  • Kumar N, Singh N, Jaggi AS (2012) Anti-stress effects of cilnidipine and nimodipine in immobilization subjected mice. Physiol Behav 105(5):1148–1155

    CAS  PubMed  Google Scholar 

  • Bhatia N, Jaggi AS, Singh N, Anand P, Dhawan R. Kaur A, Bali A, Singh N, Jaggi AS. Adaptogenic potential of curcumin in experimental chronic stress and chronic unpredictable stress-induced memory deficits and alterations in functional homeostasis. J Nat Med 2011; 65(3–4):532–543

  • Pringle NP, Mudhar HS, Collarini EJ, Richardson WD (1992) PDGF receptors in the rat CNS: during late neurogenesis, PDGF alpha-receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage. Development. 115(2):535–551

    CAS  PubMed  Google Scholar 

  • O'Donnell J, Zeppenfeld D, McConnell E, Pena S, Nedergaard M (2012) Norepinephrine: a neuromodulator that boosts the function of multiple cell types to optimize CNS performance. Neurochem Res 37(11):2496–2512

    CAS  PubMed  PubMed Central  Google Scholar 

  • Benloucif S, Bennett EL, Rosenzweig MR (1995) Norepinephrine and neural plasticity: the effects of xylamine on experience-induced changes in brain weight, memory, and behaviour. Neurobiol Learn Mem 63(1):33–42

    CAS  PubMed  Google Scholar 

  • Dayas CV, Buller KM, Day TA (2001) Medullary neurones regulate hypothalamic corticotropin-releasing factor cell responses to an emotional stressor. Neuroscience. 105(3):707–719

    CAS  PubMed  Google Scholar 

  • Tanra AJ, Kagaya A, Okamoto Y, Muraoka M, Motohashi N, Yamawaki S (1995) TJS-010, a new prescription of oriental medicine, antagonizes tetrabenazine-induced suppression of spontaneous locomotor activity in rats. Prog Neuro-Psychopharmacol Biol Psychiatry 19:963–971

    CAS  Google Scholar 

  • Satou T, Anderson AJ, Itoh T, Tamai Y, Hayashi Y, Hashimoto S (2001) Repetitive administration of tetrabenazine induces irreversible changes in locomotion and morphology of the substantia nigra in rats. Exp Toxicol Pathol 53:303–308

    CAS  PubMed  Google Scholar 

  • Chen JJ, Ondo WG, Dashtipour K, Swope DM (2012) Tetrabenazine for the treatment of hyperkinetic movement disorders: a review of the literature. Clin Ther 34:1487–1504

    Google Scholar 

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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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