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Investigating the stress attenuating potential of furosemide in immobilization and electric foot-shock stress models in mice

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Abstract

The present study was designed to investigate the antistress effect of furosemide (sodium potassium chloride co-transporter inhibitor) in immobilization and foot-shock stress-induced behavioral alterations in the mice. Acute stress was induced in Swiss albino mice either by applying electric foot shocks of 0.6-mA intensity of 1-s duration with 30-s inter-shock interval for 1 h or immobilizing for 150 min. The acute stress-induced behavioral changes were assessed by using actophotometer, hole board, open-field, and social interaction tests. Biochemically, the corticosterone levels were estimated in the serum as a biomarker of hypothalamus-pituitary-adrenal (HPA) axis. Acute stress resulted in the development of behavioral alterations and elevation of the corticosterone levels. Intraperitoneal administration of furosemide (25 and 50 mg/kg) significantly attenuated immobilization and foot-shock stress-induced behavioral changes along with normalization of the corticosterone levels. It may be concluded that furosemide produces beneficial effects in reestablishing the behavioral and biochemical alterations in immobilization and foot-shock-induced acute stress in mice.

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References

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

    Article  CAS  PubMed  Google Scholar 

  • Akil HA, Morano MI (1995) Stress. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology: the fourth generation in progress. Raven Press, New York, pp 773–785

    Google Scholar 

  • Aoki E, Shibasaki T, Kawana S (2003) Intermittent foot shock stress prolongs the telogen stage in the hair cycle of mice. Exp Dermatol 12:371–377

    Article  CAS  PubMed  Google Scholar 

  • Bali A, Jaggi AS (2013) Angiotensin as stress mediator: role of its receptor and interrelationships among other stress mediators and receptors. Pharmacol Res 76:49–57

    Article  CAS  PubMed  Google Scholar 

  • Bali A, Jaggi AS (2014) Multifunctional aspects of allopregnanolone in stress and related disorders. Prog Neuropsychopharmacol Biol Psychiatry 48:64–78

    Article  CAS  PubMed  Google Scholar 

  • Bali A, Singh N, Jaggi AS (2013) Investigations into mild electric foot shock stress-induced cognitive enhancement: possible role of angiotens in neuropeptides. J Renin-Angiotensin-Aldosterone Syst 14(3):197–203

    Article  CAS  PubMed  Google Scholar 

  • Bali A, Randhawa PK, Jaggi AS (2014) Interplay between RAS and opioids: opening the Pandora of complexities. Neuropeptides 48:249–256

    Article  CAS  PubMed  Google Scholar 

  • Beck J, Lenart B, Kintner DB, Sun D (2003) Na-K-Cl cotransporter contributes to glutamate-mediated excitotoxicity. J Neurosci 23(12):5061–5068

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Brandt C, Nozadze M, Heuchert N, Rattka M, Loscher W (2010) disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy. The. J Neurosci 25:8602–8612

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Brumback AC, Staley DW (2008) Thermodynamic regulation of NKCC1-mediated Cl- co-transport underlies plasticity of GABAA signaling in neonatal neurons. J Neurosci 6:1301–1312

    Article  Google Scholar 

  • Busquet P, Nguyen NK, Schmid E, Tanimoto N, Seeliger MW, Ben-Yosef T, Mizuno F, Akopian A, Striessnig J, Singewald N (2010) CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype. Int J Neuropsychopharmacol 13:499–513

    Article  CAS  PubMed  Google Scholar 

  • Creel S, Winnie JA Jr, Christianson D (2009) Glucocorticoid stress hormones and the effect of predation risk on elk reproduction. Proc Natl Acad Sci U S A 106(30):12388–12393

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Doron R, Lotan D, Versano Z, Benatav L, Franko M, Armoza S, Kately N, Rehavi M (2014) Escitalopram or novel herbal mixture treatments during or following exposure to stress reduce anxiety-like behavior through corticosterone and BDNF modifications. PLoS One 9:e91455

    Article  PubMed Central  PubMed  Google Scholar 

  • Francis GS, Siegel RM, Goldsmith SR, Olivari MT, Levine BT, Cohn JN (1985) Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure: activation of the neurohumoral axis. Ann Intern Med 103(1):1–6

    Article  CAS  PubMed  Google Scholar 

  • Geck PC, Pietrzyk BC, Burckhardt B (1980) Pfeiffer, Heinz E. Electrically silent cotransport of Na+, K+ and Cl- in Ehrlich cells. Biochim Biophys Acta 600:432–447

    Article  CAS  PubMed  Google Scholar 

  • Glick D, Vonredlich D, Levine S (1964) Fluorometric determination of corticosterone and cortisol in 0.02–0.05 milliliters of plasma or submilligram samples of adrenal tissue. Endocrinology 74:653–655

    Article  CAS  PubMed  Google Scholar 

  • Granados-Soto V, Arguelles CF, Alvarez-Leefmans FJ (2005) Peripheral and central antinociceptive action of Na–K–2Cl cotransporter blockers on formalin-induced nociception in rats. Pain 114:231–238

    Article  CAS  PubMed  Google Scholar 

  • Haas M, Forbush B (2000) The Na-K-Cl cotransporter of secretory epithelia. Annu Rev Physiol 62:515–534

    Article  CAS  PubMed  Google Scholar 

  • Haj-Mirzaian A, Ostadhadi S, Kordjazy N, Dehpour AR, Mehr SE (2014) Opioid/NMD A receptors blockade reverses the depressant-like behavior of foot shock stress in the mouse forced swimming test. European J Pharmacol. Article in press

  • Herman JP, Ostrander MM, Mueller NK, Figueiredo H (2005) Limbic system mechanisms of stress regulation: hypothalamo-pituitary-adrenocortical axis. Prog Neuro-Psychopharmacol Biol Psychiatry 29:1201–1213

    Article  CAS  Google Scholar 

  • Jaggi AS, Bhatia N, Kumar N, Singh N, Anand P, Dhawan R (2011) A review on animal models for screening potential anti-stress agents. Neurol Sci 32:993–1005

    Article  PubMed  Google Scholar 

  • Kasuga S, Ushijima M, Morihara N, Itakura Y, Nakata Y (1999) Effect of aged garlic extract (AGE) on hyperglycemia induced by immobilization stress in mice. Jpn J Pharmacol 114:191–197

    Article  CAS  Google Scholar 

  • Kaur R, Jaggi AS, Singh N (2009) Studies on effect of stress preconditioning in restrain stress induced behavioral alterations. Yakugaku Zasshi 130:215–221

    Article  Google Scholar 

  • Krystal AD, Sutherland J, Hochman DW (2012) Loop diuretics have anxiolytic effects in rat models of conditioned anxiety. PLoS ONE 7:e35417

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Kvetnansky R, Mikulaj L (1970) Adrenal and urinary catecholamines in rats during adaptation to repeated immobilization stress. Endocrinology 87:738–743

    Article  CAS  PubMed  Google Scholar 

  • Kvetnansky R, McCarty R, Thoa NB, Lake CR, Kopin IJ (1979) Sympatho-adrenal responses of spontaneously hypertensive rats to immobilization stress. Am J Physiol 236:H457–H462

    CAS  PubMed  Google Scholar 

  • Lim TS, Putt N, Safranski D, Chung C, Watson RR (1981) Effect of vitamin E on cell mediated immune responses and serum corticosterone in young and maturing mice. Immunology 44:289–295

    PubMed Central  CAS  PubMed  Google Scholar 

  • Maguire J, Salpekar JA (2013) Stress, seizures, and hypothalamic–pituitary–adrenal axis targets for the treatment of epilepsy. Epilepsy Behav 26:352–362

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Nardou R, Ben-Ari Y, Khalilov I (2009) Bumetanide, an NKCC1 antagonist, does not prevent formation of epileptogenic focus but blocks epileptic focus seizures in immature rat hippocampus. J Neurophysiol 101:2878–2888

    Article  CAS  PubMed  Google Scholar 

  • Nugent BM, Valenzuela CV, Simons TJ, McCarthy MM (2012) Kinases SPAK and OSR1 are upregulated by estradioland activate NKCC1 in the developing hypothalamus. J Neurosci 32(2):593–598

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Okabe A, Ohno K, Toyoda H, Yokokura M, Sato K, Fukuda A (2002) Amygdala kindling induces up-regulation of mRNA for Na+K+2Cl- cotransporter, in the rat piriform cortex. Neurosci Res 44:225–229

    Article  CAS  PubMed  Google Scholar 

  • Oriaifo SE, Otokiti I, Omogbai EK (2012) The effect of furosemide on experimentally-induced seizures in mice. J Clin Med Res 4(7):89–93

    CAS  Google Scholar 

  • Osterlund C, Spencer RL (2011) Corticosterone pretreatment suppresses stress-induced hypothalamic-pituitary-adrenal axis activity via multiple actions that vary with time, site of action, and de novo protein synthesis. J Endocrinol 208(3):311–322

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pacak K, Kvetnansky R, Palkovits M, Fukuhara K, Yadid G, Kopin IJ, Goldstein DS (1993) Adrenalectomy augments in-vivo release of norepinephrine in the paraventricular nucleus during immobilization stress. Endocrinology 133:1404–1410

    CAS  PubMed  Google Scholar 

  • Pedersen SF, O’Donnell ME, Anderson SE, Cala PM (2006) Physiology and pathophysiology of Na+/H+ exchange and Na + -K+ -2Cl- cotransport in the heart, brain, and blood. Am J Physiol Regul Integr Comp Physiol 291(1):R1–R25

    Article  CAS  PubMed  Google Scholar 

  • Pitcher HM, Cervero F (2010) Role of the NKCC1 co-transporter in sensitization of spinal nociceptive neurons. Pain 151:756–762

    Article  CAS  PubMed  Google Scholar 

  • Rabasa C, Muñoz-Abellána C, Daviua N, Nadal R, Armario A (2011) Repeated exposure to immobilization or two different foot shock intensities reveals differential adaptation of the hypothalamic–pituitary–adrenal axis. Physiol Behav 103:125–133

    Article  CAS  PubMed  Google Scholar 

  • Ravindran R, Devi RS, Samson J, Senthilvelan M (2005) Noise-stress-induced brain neurotransmitter changes and the effect of Ocimum sanctum (Linn) treatment in albino rats. J Pharmacol Sci 98:354–360

    Article  CAS  PubMed  Google Scholar 

  • Roberts PA, Pollay M, Engles C, Pendleton B, Reynolds E, Stevens FA (1987) Effect on intracranial pressure of furosemide combined with varying doses and administration rates of mannitol. J Neurosurg 66:440–446

    Article  CAS  PubMed  Google Scholar 

  • Roozendaal B, McEwen BS, Chattarji S (2009) Stress, memory and the amygdala. Rev Neurosci 10:423–433

    Article  CAS  Google Scholar 

  • Russell JM (2000) Sodium-potassium-chloride cotransport. Physiol Rev 80:211–276

    CAS  PubMed  Google Scholar 

  • Su G, Haworth RA, Dempsey RJ, Sun D (2000) Regulation of Na + -K + -Cl- cotransporter in primary astrocytes by dibutyryl cAMP and high [K(+)](o). Am J Physiol 279:1710–1721

    Google Scholar 

  • Ternacle J, Gallet R, Cognet T, Gueret P, Teiger E, Dubois-Randé JL, Lim P (2013) Should furosemide be avoided in acute right ventricular myocardial infarction? Ann Cardiol Angeiol (Paris) 62(2):95–100

    Article  CAS  Google Scholar 

  • Thapaliya K, Bhandary A, Basnet S, Aryal B (2013) Clinical status of furosemide on liver cirrhosis with portal hypertension and ascites. J Chitwan Med Coll 3(3):65–66

    Google Scholar 

  • Wallace BK, Jelks KA, O’Donnell ME (2012) Ischemia-induced stimulation of cerebral microvascular endothelial cell Na-K-Cl cotransport involves p38 and JNK MAP kinases. Am J Physiol Cell Physiol 302:C505–C517

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wang C, Shimizu-Okabe C, Watanabe K, Okabe A, Matsuzakia H, Ogawaa T, Moric N, Fukudab A, Satoa K (2002) Developmental changes in KCC1, KCC2, and NKCC1 mRNA expressions in the rat brain. Dev Brain Res 139:59–66

    Article  CAS  Google Scholar 

  • Xie Z, Currie KP, Cahill AL, Fox AP (2003) Role of Cl- co-transporters in the excitation produced by GABAA receptors in juvenile bovine adrenal chromaffin cells. J Neurophysiol 90(6):3828–3837

    Article  CAS  PubMed  Google Scholar 

  • Ye Z, Li D, Byun HS, Li L, Pan H (2012) NKCC1 upregulation disrupts chloride homeostasis in the hypothalamus and increases neuronal activity–sympathetic drive in hypertension. J Neurosci 32(25):8560–8568

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zemkova HW, Bjelobaba I, Tomic M, Zemkova H, Stojilkovic SS (2008) Molecular, pharmacological and functional properties of GABA(A) receptors in anterior pituitary cells. J Physiol 586(13):3097–3111

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors are grateful to the Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India, for supporting this study and providing technical facilities for the work.

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  1. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, India

    Aalamjeet Kaur, Anjana Bali, Nirmal Singh & Amteshwar Singh Jaggi

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  1. Aalamjeet Kaur
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Correspondence to Amteshwar Singh Jaggi.

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Kaur, A., Bali, A., Singh, N. et al. Investigating the stress attenuating potential of furosemide in immobilization and electric foot-shock stress models in mice. Naunyn-Schmiedeberg's Arch Pharmacol 388, 497–507 (2015). https://doi.org/10.1007/s00210-015-1084-7

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