AMELIORATIVE EFFECTS OF ANGIOTENSIN RECEPTOR BLOCKERS AGAINST SCOPOLAMINE-INDUCED MEMORY IMPAIRMENT IN RATS

Authors

  • Debasree Deb Department of Pharmacology, Melaka Manipal Medical College, Manipal University, Manipal Campus, Manipal 576104, India
  • Veena Nayak Department of Pharmacology, Kasturba Medical College, Manipal University, Manipal 576104, India
  • LAXMINARAYANA BAIRY KURADY Department of Pharmacology, Kasturba Medical College, Manipal university, Manipal-576104 http://orcid.org/0000-0002-1828-6946
  • Mohandas Rao Department of Anatomy, Melaka Manipal Medical College, Manipal University, Manipal Campus, Manipal 576104, India

Abstract

ABSTRACT
Objective: The present study was designed to investigate the cognitive enhancing property of angiotensin receptor blockers (ARBs) in scopolamineinduced
amnesic rats.
Methods: A total of 42 male Wistar rats were divided into seven groups. Group 1 received 2% gum acacia orally for 4 weeks, Group 2 received normal
saline, and Group 3 received scopolamine (2 mg/kg/i.p.) as a single dose. Groups 4 and 5 received telmisartan (1.80 mg/kg and 3.60 mg/kg, respectively)
while Groups 6 and 7 received losartan (2.25 mg/kg and 4.50 mg/kg, respectively), orally for 4 weeks, followed by scopolamine (2 mg/kg/i.p.) given
45 minutes prior to experimental procedure. Evaluation of learning and memory was assessed by using morris water maze test followed by estimation
of hippocampal choline acetyltransferase (ChAT) activity. Alterations in hippocampal morphology and degree of neuronal survival were also analyzed
following drug treatments.
Results: Scopolamine-induced marked impairment of memory in the behavioral test which correlated with reduced ChAT activity and morphological
changes in the hippocampus. Treatment with higher doses of telmisartan and losartan improved memory deficits in scopolamine-induced amnesic
rats while increasing the hippocampal ChAT activity. The treatments also attenuated hippocampal degeneration and increased the number of surviving
neurons in hippocampus scopolamine-induced amnesic rats.
Conclusion: Pre-treatment with ARBs attenuated scopolamine-induced memory deficits which may be attributed to their angiotensin receptor
blockade property or to improved cholinergic activity, and thus highlighting the potential of these drugs in dementia.
Keywords: Angiotensin scopolamine, Amnesia, Angiotensin receptor blockers, Losartan, telmisartan

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Author Biographies

Debasree Deb, Department of Pharmacology, Melaka Manipal Medical College, Manipal University, Manipal Campus, Manipal 576104, India

Lecturer in Pharmacology

Veena Nayak, Department of Pharmacology, Kasturba Medical College, Manipal University, Manipal 576104, India

Assoicate Professor, Pharmacology

LAXMINARAYANA BAIRY KURADY, Department of Pharmacology, Kasturba Medical College, Manipal university, Manipal-576104

Professor of Pharmacology

Mohandas Rao, Department of Anatomy, Melaka Manipal Medical College, Manipal University, Manipal Campus, Manipal 576104, India

Professor and Head, anatomy

References

REFERENCES

Ballard C, Corbett A. Management of neuropsychiatric symptoms in

people with dementia. CNS Drugs 2010;24(9):729-39.

Ott A, Breteler MM, van Harskamp F, Claus JJ, van der Cammen TJ,

Grobbee DE, et al. Prevalence of Alzheimer’s disease and vascular

dementia: association with education. The Rotterdam study. BMJ

;310(6985):970-3.

Stahl SM. The new cholinesterase inhibitors for Alzheimer’s disease,

Part 2: illustrating their mechanisms of action. J Clin Psychiatry

;61(11):813-4.

Froestl W, Muhs A, Pfeifer A. Cognitive enhancers (nootropics). Part 1:

drugs interacting with receptors. J Alzheimers Dis 2012;32(4):793-887.

Ciobica A, Bild W, Hritcu L, Haulica I. Brain renin-angiotensin system in

cognitive function: pre-clinical findings and implications for prevention

and treatment of dementia. Acta Neurol Belg 2009;109(3):171-80.

Kazama K, Anrather J, Zhou P, Girouard H, Frys K, Milner TA, et al.

Angiotensin II impairs neurovascular coupling in neocortex through

NADPH oxidase-derived radicals. Circ Res 2004;95(10):1019-26.

Wei W, Whaley-Connell TA, Chen K, Habibi J, Uptergrove G, Clark S,

et al. NADPH oxidase contributes to vascular inflammation, insulin

resistance, and remodeling in the transgenic (mRen2) rat. Hypertension

;50(2):384-91.

Baltatu O, Bader M. Brain renin-angiotensin system. Lessons from

functional genomics. Neuroendocrinology 2003;78(5):253-9.

McKinley MJ, Albiston AL, Allen AM, Mathai ML, May CN,

McAllen RM, et al. The brain renin-angiotensin system: location and

physiological roles. Int J Biochem Cell Biol 2003;35(6):901-18.

Gard PR. The role of angiotensin II in cognition and behaviour. Eur J

Pharmacol 2002;438(1-2):1-14.

Savaskan E, Hock C, Olivieri G, Bruttel S, Rosenberg C, Hulette C,

et al. Cortical alterations of angiotensin converting enzyme, angiotensin

II and AT1 receptor in Alzheimer’s dementia. Neurobiol Aging

;22(4):541-6.

Ge J, Barnes NM. Alterations in angiotensin AT1 and AT2 receptor

subtype levels in brain regions from patients with neurodegenerative

disorders. Eur J Pharmacol 1996;297(3):299-306.

Gard PR. Cognitive-enhancing effects of angiotensin IV. BMC Neurosci

3;9 Suppl 2:S15.

Barreras A, Gurk-Turner C. Angiotensin II receptor blockers. Proc

(Bayl Univ Med Cent) 2003;16(1):123-6.

Paget GE, Barnes JM. Evaluation of drug activities. In: Lawrence DR,

Bacharcach AL, editors. Pharmacometrics. New York: Academic Press;

p. 161.

Zanotti A, Valzelli L, Toffano G. Reversal of scopolamine-induced

amnesia by phosphatidylserine in rats. Psychopharmacology (Berl)

;90(2):274-5.

Wang J, Wang X, Lv B, Yuan W, Feng Z, Mi W, et al. Effects of Fructus

Akebiae on learning and memory impairment in a scopolamine-induced

animal model of dementia. Exp Ther Med 2014;8(2):671-5.

Dhwaj VA, Singh R. Reversal effect of asparagus racemosus wild

(liliaceae) root extract on memory deficits of mice. Int J Drug Dev Res

;3(2):314-23.

Morris R. Developments of a water-maze procedure for studying spatial

learning in the rat. J Neurosci Methods 1984;11(1):47-60.

Glowinski J, Iversen LL. Regional studies of catecholamines in the rat

brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]

dopa in various regions of the brain. J Neurochem 1966;13(8):655-69.

Osmekhina E, Neubauer A, Klinzing K, Myllyharju J, Neubauer P.

Sandwich ELISA for quantitative detection of human collagen prolyl

-hydroxylase. Microb Cell Fact 2010;9:48.

Bejar C, Wang RH, Weinstock M. Effect of rivastigmine on

scopolamine-induced memory impairment in rats. Eur J Pharmacol

Asian J Pharm Clin Res, Vol 9, Issue 2, 2016, 335-341

Deb et al.

;383(3):231-40.

Jones RW, Wesnes KA, Kirby J. Effects of NMDA modulation in

scopolamine dementia. Ann N Y Acad Sci 1991;640:241-4.

Drachman DA, Leavitt J. Human memory and the cholinergic system.

A relationship to aging? Arch Neurol 1974;30(2):113-21.

Sharma B, Singh N, Singh M. Modulation of celecoxib- and

streptozotocin-induced experimental dementia of Alzheimer’s disease

by pitavastatin and donepezil. J Psychopharmacol 2008;22(2):162-71.

Austen B, Christodoulou G, Terry JE. Relation between cholesterol

levels, statins and Alzheimer’s disease in the human population. J Nutr

Health Aging 2002;6(6):377-82.

Alger BE, Nagode DA, Tang AH. Muscarinic cholinergic receptors

modulate inhibitory synaptic rhythms in hippocampus and neocortex.

Front Synaptic Neurosci 2014;6:18.

Wenk H, Bigl V, Meyer U. Cholinergic projections from magnocellular

nuclei of the basal forebrain to cortical areas in rats. Brain Res Reviews

;2(3):295-316.

Falsafi SK, Deli A, Höger H, Pollak A, Lubec G. Scopolamine

administration modulates muscarinic, nicotinic and NMDA receptor

systems. PLoS One 2012;7(2):e32082.

Heo HJ, Suh YM, Kim MJ, Choi SJ, Mun NS, Kim HK, et al. Daidzein

activates choline acetyltransferase from MC-IXC cells and improves

drug-induced amnesia. Biosci Biotechnol Biochem 2006;70(1):107-11.

Xiang GQ, Tang SS, Jiang LY, Hong H, Li Q, Wang C, et al. PPAR?

agonist pioglitazone improves scopolamine-induced memory

impairment in mice. J Pharm Pharmacol 2012;64(4):589-96.

Shinoe T, Matsui M, Taketo MM, Manabe T. Modulation of synaptic

plasticity by physiological activation of M1 muscarinic acetylcholine

receptors in the mouse hippocampus. J Neurosci 2005;25(48):11194-200.

Antonova E, Parslow D, Brammer M, Simmons A, Williams S,

Dawson GR, et al. Scopolamine disrupts hippocampal activity during

allocentric spatial memory in humans: an fMRI study using a virtual

reality analogue of the Morris Water Maze. J Psychopharmacol

;25(9):1256-65.

Scoville WB, Milner B. Loss of recent memory after bilateral

hippocampal lesions. J Neurol Neurosurg Psychiatry 1957;20(11):11-21.

Bodiga LV, Bodiga S. Renin angiotensin system in cognitive function

and dementia. Asian J Neurosci 2013;2013:Article ID: 102602, 18.

Barnes JM, Barnes NM, Costall B, Coughlan J, Horovitz ZP, Kelly ME,

et al. ACE inhibition and cognition. In: McGregor GA, Sever PS,

editors. Current Advances in ACE Inhibition. Proceedings of an

international Symposium. Edinburgh: Churchill Livingstone; 1989.

p. 159-71.

Wright JW, Harding JW. The angiotensin AT4 receptor subtype as a target

for the treatment of memory dysfunction associated with Alzheimer’s

disease. J Renin Angiotensin Aldosterone Syst 2008;9(4):226-37.

Pederson ES, Harding JW, Wright JW. Attenuation of scopolamineinduced

spatial learning

impairments by

an angiotensin IV

analog.

Regul

Pept 1998;74(2-3):97-103.

Micossi LG, Tomaszewicz M, Bielarczyk H, Luszawska D, Trognoni A,

Szutowicz A. Effect of angiotensin II and eledoisin on cholinergic

neurons in rat hippocampus. Neuroreport 1992;3(1):36-8.

Lenkei Z, Palkovits M, Corvol P, Llorens-Cortès C. Expression of

angiotensin type-1 (AT1) and type-2 (AT2) receptor mRNAs in the adult

rat brain: a functional neuroanatomical review. Front Neuroendocrinol

;18(4):383-439.

Denny JB, Polan-Curtain J, Wayner MJ, Armstrong DL.

Angiotensin II blocks hippocampal long-term potentiation. Brain Res

;567(2):321-4.

Tashev R, Stefanova M. Hippocampal asymmetry in angiotensin II

modulatory effects on learning and memory in rats. Acta Neurobiol Exp

(Wars) 2015;75(1):48-59.

Santos MJ, Quintanilla RA, Toro A, Grandy R, Dinamarca MC,

Godoy JA, et al. Peroxisomal proliferation protects from beta-amyloid

neurodegeneration. J Biol Chem 2005;280(49):41057-68.

Mogi M, Li JM, Tsukuda K, Iwanami J, Min LJ, Sakata A, et al.

Telmisartan prevented cognitive decline partly due to PPAR-gamma

activation. Biochem Biophys Res Commun 2008;375(3):446-9.

Harrold M. Angiotensin converting enzyme inhibitors, antagonists and

calcium channel blockers. In: William DA, Lemke TL, editors. Foye’s

Principles of Medicinal Chemistry. 5th ed. Baltimore, MD: Lippincott

Williams & Wilkins; 2002. p. 454-7.

Kakuta H, Sudoh K, Sasamata M, Yamagishi S. Telmisartan has the

strongest binding affinity to angiotensin II type 1 receptor: comparison

with other angiotensin II type 1 receptor blockers. Int J Clin Pharmacol

Res 2005;25(1):41-6.

Michel MC, Foster C, Brunner HR, Liu L. A systematic comparison

of the properties of clinically used angiotensin II type 1 receptor

antagonists. Pharmacol Rev 2013;65(2):809-48.

Wienen W, Entzeroth M, van Meel JC, Stangier J, Busch U, Ebner T,

et al. A review on telmisartan: A novel, long-acting angiotensin IIreceptor

antagonist. Cardiovasc Drug Rev 2010;18:127-56.

Ribadeneira MD, Aungst BJ, Eyermann CJ, Huang SM. Effects of

structural modifications on the intestinal permeability of angiotensin II

receptor antagonists and the correlation of in vitro, in situ, and in vivo

absorption. Pharm Res 1996;13(2):227-33.

Kivlighn SD, Zingaro GJ, Gabel RA, Broten TP, Chang RS,

Ondeyka DL, et al. In vivo pharmacology of an angiotensin AT1

receptor antagonist with balanced affinity for AT2 receptors. Eur J

Pharmacol 1995;294(2-3):439-50.

Guimond MO, Gallo-Payet N. How does angiotensin AT(2) receptor

activation help neuronal differentiation and improve neuronal

pathological situations? Front Endocrinol (Lausanne) 2012;3:164.

Gallo-Payet N, Guimond MO, Bilodeau L, Wallinder C, Alterman

M, Hallberg A. Angiotensin II, a neuropeptide at the frontier between

endocrinology and neuroscience: Is there a link between the angiotensin

II Type 2 receptor and Alzheimer’s disease? Front Endocrinol

(Lausanne) 2011;2:17.

Published

01-03-2016

How to Cite

Deb, D., V. Nayak, L. B. . KURADY, and M. Rao. “AMELIORATIVE EFFECTS OF ANGIOTENSIN RECEPTOR BLOCKERS AGAINST SCOPOLAMINE-INDUCED MEMORY IMPAIRMENT IN RATS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 9, no. 2, Mar. 2016, pp. 335-41, https://mail.innovareacademics.in/journals/index.php/ajpcr/article/view/10821.

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