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Current Clinical Pharmacology


ISSN (Print): 1574-8847
ISSN (Online): 2212-3938

General Research Article

Comparative Effectiveness of Agmatine and Choline Treatment in Rats with Cognitive Impairment Induced by AlCl3 and Forced Swim Stress

Author(s): Hira Rafi*, Fahad Ahmad, Javaria Anis, Ruba Khan, Hamna Rafiq and Muhammad Farhan

Volume 15, Issue 3, 2020

Page: [251 - 264] Pages: 14

DOI: 10.2174/1574884714666191016152143


Aim: Endogenous agmatine has a significant role in learning and memory processes as a neurotransmitter. Various studies described the physiological role of endogenous agmatine in learning and memory of multiple cognitive tasks suggesting elevated levels of agmatine during the learning process in the rat brain. Dietary intake of choline showed correlation with cognitive functions in human subjects and treatment with choline supplements validated the ability to diminish learning and cognitive impairment dementias.

Methods: 36 Albino rats were equally divided into three groups previously: a) control-water, b) Test I - AlCl3 (100 mg/Kg body weight), and c) Test II - Forced swim stress (FSS) for 14 days. On the next day of AlCl3 and FSS last administration, animals were allocated into further three groups and received the following treatments: a. water was given orally to the control group, b. Agmatine (100 mg/Kg Body Weight) group, and c. Choline (100 mg/Kg Body Weight) group for the next 14 days. Behaviors were assessed in Light/Dark Box, Open Field, Novel Object Recognition Test (NOR), T Maze Test, and Morris Water Maze Test.

Results: Animals administered with agmatine demonstrated increased time spent in bright areas of light/dark box and square crossed while improved spatial memory in Morris water maze and T maze test and enhanced discrimination of novel object in NOR were observed in learning and memory paradigms along with choline.

Conclusion: The present study determines that agmatine at the dose of (100 mg/kg body weight) attenuates memory and cognitive impairment in comparison with choline supplements.

Keywords: Agmatine, choline, learning, memory, cognitive impairment, morris water maze test.

Graphical Abstract
Liu P, Collie ND, Chary S, Jing Y, Zhang H. Spatial learning results in elevated agmatine levels in the rat brain. Hippocampus 2008; 18(11): 1094-8.
[] [PMID: 18680141]
Rushaidhi M, Jing Y, Zhang H, Liu P. Participation of hippocampal agmatine in spatial learning: An in vivo microdialysis study. Neuropharmacology 2013; 65: 200-5.
[] [PMID: 23116777]
Leitch B, Shevtsova O, Reusch K, Bergin DH, Liu P. Spatial learning-induced increase in agmatine levels at hippocampal CA1 synapses. Synapse 2011; 65(2): 146-53.
[] [PMID: 20572157]
Seo S, Liu P, Leitch B. Spatial learning-induced accumulation of agmatine and glutamate at hippocampal CA1 synaptic terminals. Neuroscience 2011; 192: 28-36.
[] [PMID: 21777660]
Moinard C, Cynober L, de Bandt JP. Polyamines: Metabolism and implications in human diseases. Clin Nutr 2005; 24(2): 184-97.
[] [PMID: 15784477]
Liu P, Jing Y, Collie ND, Chary S, Zhang H. Memory-related changes in L-citrulline and agmatine in the rat brain. Hippocampus 2009; 19(7): 597-602.
[] [PMID: 19173225]
Utkan T, Gocmez SS, Regunathan S, Aricioglu F. Agmatine, a metabolite of L-arginine, reverses scopolamine-induced learning and memory impairment in rats. Pharmacol Biochem Behav 2012; 102(4): 578-84.
[] [PMID: 22796489]
Moosavi M, Khales GY, Abbasi L, Zarifkar A, Rastegar K. Agmatine protects against scopolamine-induced water maze performance impairment and hippocampal ERK and Akt inactivation. Neuropharmacology 2012; 62(5-6): 2018-23.
[] [PMID: 22248637]
Bergin DH, Liu P. Agmatine protects against beta-amyloid25-35-induced memory impairments in the rat. Neuroscience 2010; 169(2): 794-811.
[] [PMID: 20457225]
Poly C, Massaro JM, Seshadri S, et al. The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. Am J Clin Nutr 2011; 94(6): 1584-91.
[] [PMID: 22071706]
Parnetti L, Mignini F, Tomassoni D, Traini E, Amenta F. Cholinergic precursors in the treatment of cognitive impairment of vascular origin: Ineffective approaches or need for re-evaluation? J Neurol Sci 2007; 257(1-2): 264-9.
[] [PMID: 17331541]
Sanders LM, Zeisel SH. Choline: Dietary requirements and role in brain development. Nutr Today 2007; 42(4): 181-6.
[] [PMID: 18716669]
Albuquerque EX, Pereira EFR, Alkondon M, Rogers SW. Mammalian nicotinic acetylcholine receptors: From structure to function. Physiol Rev 2009; 89(1): 73-120.
[] [PMID: 19126755]
Boccia MM, Blake MG, Krawczyk MC, Baratti CM. Hippocampal α7 nicotinic receptors modulate memory reconsolidation of an inhibitory avoidance task in mice. Neuroscience 2010; 171(2): 531-43.
[] [PMID: 20832455]
Mufson EJ, Counts SE, Perez SE, Ginsberg SD. Cholinergic system during the progression of Alzheimer’s disease: Therapeutic implications. Expert Rev Neurother 2008; 8(11): 1703-18.
[] [PMID: 18986241]
Grothe M, Heinsen H, Teipel SJ. Atrophy of the cholinergic Basal forebrain over the adult age range and in early stages of Alzheimer’s disease. Biol Psychiatry 2012; 71(9): 805-13.
[] [PMID: 21816388]
Burke RM, Norman TA, Haydar TF, et al. BMP9 ameliorates amyloidosis and the cholinergic defect in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 2013; 110(48): 19567-72.
[] [PMID: 24218590]
Mellott TJ, Pender SM, Burke RM, Langley EA, Blusztajn JK. IGF2 ameliorates amyloidosis, increases cholinergic marker expression and raises BMP9 and neurotrophin levels in the hippocampus of the APPswePS1dE9 Alzheimer’s disease model mice. PLoS One 2014; 9(4)e94287
[] [PMID: 24732467]
Kamphuis W, Mamber C, Moeton M, et al. GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease. PLoS One 2012; 7(8)e42823
[]] [PMID: 22912745]
Gaurav G, Chellappan DK, Agarwal M, et al. Ashwathanarayana M, Nammi S, Pabreja K, Dua K Pharmacological evaluation of the recuperative effect of morusin against Aluminium trichloride (AlCl3)-induced memory impairment in rats. Cent Nerv Syst Agents Med Chem 2017; 17(3): 196-200.
Badowska-Szalewska E, Spodnik E, Klejbor I, Moryś J. Effects of chronic forced swim stress on hippocampal Brain-Derived Neutrophic Factor (BDNF) and its receptor (TrkB) immunoreactive cells in juvenile and aged rats. Acta Neurobiol Exp (Warsz) 2010; 70(4): 370-81.
[PMID: 21196945]
Rafi H, Rafiq H, Hanif I, Rizwan R, Farhan M. Chronic ag-matine treatment modulates behavioral deficits induced by chronic unpredictable stress in wistar rats. J Pharm Biol Sci 2018; 6(3): 80-9.
Waddell J, Mooney SM. Choline and working memory train-ing improve cognitive deficits caused by prenatal exposure to ethanol. Nutrients 2017; 9(10): 1080.
[] [PMID: 28961168]
Choleris E, Thomas AW, Kavaliers M, Prato FS. A detailed ethological analysis of the mouse open field test: effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field. Neurosci Biobehav Rev 2001; 25(3): 235-60.
[] [PMID: 11378179]
Crawley J, Goodwin FK. Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav 1980; 13(2): 167-70.
[] [PMID: 6106204]
Zimmerberg B, Sukel HL, Stekler JD. Spatial learning of adult rats with fetal alcohol exposure: Deficits are sex-dependent. Behav Brain Res 1991; 42(1): 49-56.
[] [PMID: 2029344]
Morris RGM, Stewart CA. The water maze Behavioral Neuroscience, A Practical Approach. Oxford: IRL Press at Oxford University Press 1993; pp. 107-22.
Rebai O, Djebli NE. Chronic exposure to aluminum chloride in mice: Exploratory behaviors and spatial learning. Adv Biol Res (Faisalabad) 2008; 2(1-2): 26-33.
Goulart BK, de Lima MN, de Farias CB, et al. Ketamine impairs recognition memory consolidation and prevents learning-induced increase in hippocampal brain-derived neurotrophic factor levels. Neuroscience 2010; 167(4): 969-73.
[] [PMID: 20338225]
Liu P, Bergin DH. Differential effects of i.c.v. microinfusion of agmatine on spatial working and reference memory in the rat. Neuroscience 2009; 159(3): 951-61.
[] [PMID: 19356679]
Liu P, Chary S, Devaraj R, et al. Effects of aging on agmatine levels in memory-associated brain structures. Hippocampus 2008; 18(9): 853-6.
[] [PMID: 18481282]
Blusztajn JK, Wurtman RJ. Choline and cholinergic neurons. Science 1983; 221(4611): 614-20.
[] [PMID: 6867732]
Arteni NS, Lavinsky D, Rodrigues AL, Frison VB, Netto CA. Agmatine facilitates memory of an inhibitory avoidance task in adult rats. Neurobiol Learn Mem 2002; 78(2): 465-9.
[] [PMID: 12431430]
Liu P, Collie ND. Behavioral effects of agmatine in naive rats are task- and delay-dependent. Neuroscience 2009; 163(1): 82-96.
[] [PMID: 19482065]

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