Drug Res (Stuttg) 2017; 67(01): 59-64
DOI: 10.1055/s-0042-118172
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Protective Effect of Irbesartan an Angiotensin (AT1) Receptor Antagonist in Unpredictable Chronic Mild Stress Induced Depression in Mice

M. Ayyub
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University), Hamdard Nagar, New Delhi, India
,
A. K. Najmi
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University), Hamdard Nagar, New Delhi, India
,
M. Akhtar
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University), Hamdard Nagar, New Delhi, India
› Author Affiliations
Further Information

Publication History

received 18 July 2016

accepted 26 September 2016

Publication Date:
18 October 2016 (online)

Abstract

Objective: Oxidative stress and alternation of renin-angiotensin system has been implicated in the pathophysiology of various cardio vascular, endocrine including mood and anxiety disorders. The present study evaluated the role of irbesartan in stress induced different models of depression.

Materials and method: Mice were treated with irbesartan (40 mg/kg), fluoxetine (25 mg/kg) alone in combination orally. Drugs treatment started after 2 weeks from the beginning of the unpredictable mild stress (UCMS) protocol. Behavioural tests were performed on week 6, at least 24 h after the last treatment. Modified forced swim test (MFST), tail suspension test (TST) and open field test (OFT) were used followed by antioxidant markers and 5-HT levels determination.

Result: Irbesartan increased swimming, climbing and decreased immobility times in MFST, decrease immobility time in TST. Irbesartan also increased no. of field crossings; rearings and also increased time spent in the centre of OFT. Thus, antidepressant like activity in UCMS mice was observed. Combination of irbesartan with fluoxetine showed potentiating effect of behavioural parameters in all animal models. Combination groups also showed antioxidant effects and elevated the 5-HT levels in UCMS mice.

Conclusion: Chronic administration of Irbesartan exerted antidepressant like effect, reduced oxidative stress and elevated brain 5-HT levels.

 
  • References

  • 1 World Health Organization Media Centre, Fact sheet No. 369; 2012, October
  • 2 Dumais A, Leisage AD, Alda M et al. Risk factors for suicide completion in major depression: A case control study impulsive and aggressive behaviour in men. J Pschiat 2005; 162: 2116-2126
  • 3 Vander KK, Van Hout H, Marwijk H et al. Depression and the risk for cardiovascular diseases: systematic review and meta analysis. Int J Geriat Psychiatry 2007; 22: 613-626
  • 4 Irwin MR. Depression and Risk of Cancer Progression: An Elusive Link. J Clin Oncology 2007; 25: 2343-2344
  • 5 Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 1998; 55: 580-592
  • 6 Nguyen DCA, Touyz RM. Cell signalling of angiotensin II on vascular tone: novel mechanisms. Curr Hypertens Rep 2011; 13: 122-128
  • 7 Guimond M-O, Gallo-Payet N. The Angiotensin II Type 2 Receptor in Brain Functions: An Update. Int J Hyperten 2012; 2012 Article ID 351758, 18 pages http://dx.doi.org/10.1155/2012/351758
  • 8 Liu F, Havens J, Yu Q et al. The link between angiotensin II-mediated anxiety and mood disorders with NADPH oxidase-induced oxidative stress. Int J Physiol Pathophysio Pharmacol 2012; 4: 28-35
  • 9 Dulawa SC, Holick KA, Gundersen B et al. Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacol 2004; 29: 1321-1330
  • 10 Shelton RC. The molecular neurobiology of depression. Psychiatr Clin North Am 2007; 30: 1-11
  • 11 Warren DT, Benjamin S, Macuid DR et al. AGTR1 gene variation: association with depression and fronto temporal morphology. Psychiatry Res 2012; 202: 104-109
  • 12 Ping G, Qian W, Song G et al. Valsartan reverses depressive/anxiety-like behavior and induces hippocampal neurogenesis and expression of BDNF protein in unpredictable chronic mild stress mice. Pharmacol Biochem Behav 2014; 124: 5-12
  • 13 Nollet M, Galliard P, Minier F et al. Activation of orexin neurons in dorsomedial/perifornical hypothalamus and antidepressant reversal in a rodent model of depression. Neuropharmacology 2011; 61: 336-346
  • 14 Brown GW. Life events and affective disorders: Replications and limitations. Psychosom Med 1993; 55: 248-259
  • 15 Porsolt RD. Depression: a new animal model sensitive to antidepressant treatments. Nature 1977; 266: 730-732
  • 16 Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviours: a review. Eur J Pharmacol 2003; 463: 3-33
  • 17 Steru L, Chermat R, Thierry B et al. The automated tail suspension test: a computerized device which differentiates psychotropic drugs. Prog Neuropsychopharmacol Biol Psychiatry 1985; 11: 659-671
  • 18 Cryan JF, Page ME, Lucki I. Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test. Eur J Pharmacol 2002; 436: 197-205
  • 19 Ripoll N, Denis J, Paul D et al. Antidepressant-like effects in various mice strains in the tail suspension test. J Neu Bio Rev 2003; 143: 193-200
  • 20 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358
  • 21 Ellman GL. Tissue sulfhydryl group. Arch Biochem Biophys 1959; 82: 70-77
  • 22 Sedlak J, Lindsay RH. Estimation of total protein bound and non protein sulfhydryl group in tissue with Ellman’s reagent. Anal Biochem 1968; 25: 192-220
  • 23 Claiborne A, Greenworld RA. Handbook of method of oxygen free radical research. 1985. Boca Rated FL: CRC Press; 283-284
  • 24 Curzon G, Green AR. Rapid method for the determination of 5- hydroxyl tryptamine and 5-hydroxy indole acetic acid in small regions of rat brain. Life Sci Oxford 1968; 7: 653-655
  • 25 Lowry OH, Rosenbrough NJ, Farr AL et al. Protein measurement with Folin phenol reagent. J Bio Chem 1951; 193: 265-275
  • 26 Braszko JJ. AT (2) but not AT (1) receptor antagonism abolishes angiotensin II increase of the acquisition of condition avoidance responses in rats. Beh Brain Res 2002; 131: 79-86
  • 27 Braszko JJ. Valsartan abolishes most of the memory improving effects of intracerebroventricular angiotensin II in rats. Clin Exp Hyperten 2005; 27: 635-649
  • 28 Schildkraut JJ, Kety SS. Biogenic amines and emotion. Science 1967; 156: 21-37
  • 29 Floyd RA, Carney JM. Free radical damage to protein and DNA: mechanism involved and relevant observation on brain undergoing oxidative stress. Ann Neurol 1992; 32: S22-S27
  • 30 Pong K. Oxidative stress in neurodegenerative diseases: therapeutic implications for superoxide dismutase mimetic. Exp Opin Biol Ther 2003; 3: 127-139
  • 31 Zaidi SM, Banu N. Antioxidant potential of vitamin A, E and C in modulating oxidative stress in rat brain. Clin Chim Acta 2004; 340: 229-233
  • 32 Po SI, Tsang Wai TS. et al. Saralasin, a Nonspecific Angiotensin II Receptor Antagonist, Attenuates Oxidative Stress and Tissue Injury in Cerulein-Induced Acute Pancreatitis. Pancreas 2003; 26: 224-229
  • 33 Zafir A, Banu N. Antioxidant potential of fluoxetine in comparison to Curcuma longa in restraint-stressed rats. Eu J Pharmacol 2007; 572: 23-31
  • 34 Djordjevic J, Djordjevic A, Adzic M et al. Fluoxetine affects antioxidant system and promotes apoptotic signalling in Wistar rat liver. Eu J Pharmcol 2011; 659: 61-66
  • 35 Windle M, Windle RC. Recurrent depression, cardiovascular disease and diabetes among middle aged and older adult women. J Affect Disord 2013; 150: 895-902
  • 36 Rueda B, Perez-Garcia AM. Coping strategies, depressive symptoms and quality of life in hypertensive patients: meditational and prospective relations. Psycho Health 2013; 28: 1152-1170
  • 37 Gard PR. Angiotensin as target for the treatment of Alzheimer’s disease, anxiety and depression. Exp Open Ther Targets 2004; 8: 7-14
  • 38 Liano Lopez LH, Caif F, Garcia S et al. Anxiolytic-like effect of losartan injected into amygdala of the acutely stressed rats. Pharmcol Rep 2012; 64: 54-63