AMELIORATION OF ANXIOLYTIC BEHAVIOR IN INTRACEREBROVENTRICULAR COLCHICINE INJECTED RATS BY NAPROXEN
Abstract
Objective: Anxiety behavior in experimental model of Alzheimer's disease (AD) in rats by intracerebroventricular (ICV) injection of colchicine is
important to characterize this animal model, but it has not been sufficiently investigated in this animal model. The different attributes of anxiety
behavior in ICV colchicine injected rats (ICIR) was studied, and the effects of naproxen, a non-steroidal anti-inflammatory drug on the anxiety status
of these AD animals were assessed since in earlier studies naproxen protected cognitive impairments and neurodegeneration in ICIR.
Methods: The anxiety status was assessed in an elevated open field with a novel object in two study durations (14-day and 21-day study). After
measuring the anxiety behavior in two study durations, rats were sacrificed, and blood was collected for measuring the serum corticosterone (CORT)
level.
Results: Anxiolytic behavior along with lower CORT level was observed in ICIR in both the 14- and 21-day studies. After p.o. administration of
different doses of naproxen (5, 10, 20 mg/kg body wt.) in ICIR, this anxiolytic behavior along with low serum CORT level showed gradual recovery and
eventually both the parameters attained normal level at the dose of 20 mg/kg body weight in 21-day study.
Conclusion: The present study showed an anxiolytic behavior in ICIR, and which may result from the colchicine induced neurodegeneration along
with the impaired activity of the hypothalamo-pituitary-adrenal axis. Some parameters appeared to be sensitive for determination of anxiety status
in this model.
Keywords: Colchicine, Anxiolytic, Naproxen, Corticosterone, Alzheimer's disease.
Downloads
References
Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer
disease in the US population: Prevalence estimates using the 2000
census. Arch Neurol 2003;60(8):1119-22.
Chung JA, Cummings JL. Neurobehavioral and neuropsychiatric
symptoms in Alzheimer’s disease: Characteristics and treatment.
Neurol Clin 2000;18(4):829-46.
Vloeberghs E, Van Dam D, Franck F, Staufenbiel M, De Deyn PP.
Mood and male sexual behaviour in the APP23 model of Alzheimer’s
disease. Behav Brain Res 2007;180():146-51.
Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet
;368:387-403.
Benedikz E, Kloskowska E, Winblad B. The rat as an animal model of
Alzheimer’s disease. J Cell Mol Med 2009;13(6):1034-42.
Touma C, Ambrée O, Görtz N, Keyvani K, Lewejohann L, Palme R, et al.
Age- and sex-dependent development of adrenocortical hyperactivity
in a transgenic mouse model of Alzheimer’s disease. Neurobiol Aging
;25(7):893-904.
Reiserer RS, Harrison FE, Syverud DC, McDonald MP. Impaired
spatial learning in the APPSwe PSEN1DeltaE9 bigenic mouse model
of Alzheimer’s disease. Genes Brain Behav 2007;6(1):54-65.
Liu Y, Yoo MJ, Savonenko A, Stirling W, Price DL, Borchelt DR,
et al. Amyloid pathology is associated with progressive monoaminergic
neurodegeneration in a transgenic mouse model of Alzheimer’s disease.
J Neurosci 2008;28(51):13805-14.
Pinton S, da Rocha JT, Gai BM, Nogueira CW. Sporadic dementia
of Alzheimer’s type induced by streptozotocin promotes anxiogenic
behavior in mice. Behav Brain Res 2011;223(1):1-6.
Ennaceur A, Michalikova S, Chazot PL. Models of anxiety: Responses
of rats to novelty in an open space and an enclosed space. Behav Brain
Res 2006;171(1):26-49.
Emerich DF, Walsh TJ. Ganglioside AGF2 promotes task-specific
recovery and attenuates the cholinergic hypofunction induced by
AF64A. Brain Res 1990;527(2):299-307.
Bensimon G, Chermat R. Microtubule disruption and cognitive defects:
Effect of colchicine on learning behavior in rats. Pharmacol Biochem
Behav 1991;38(1):141-5.
Shigematsu K, McGeer PL. Accumulation of amyloid precursor protein
in neurons after intraventricular injection of colchicine. Am J Pathol
;140(4):787-94.
Kumar A, Seghal N, Naidu PS, Padi SS, Goyal R. Colchicines-induced
neurotoxicity as an animal model of sporadic dementia of Alzheimer’s
type. Pharmacol Rep 2007;59(3):274-83.
Kumar A, Seghal N, Padi SV, Naidu PS. Differential effects of
cyclooxygenase inhibitors on intracerebroventricular colchicineinduced
dysfunction and oxidative stress
in rats. Eur J Pharmacol
;551(1-3):58-66.
Pitchaimani V, Arumugam S, Thandavarayan RA, Thiyagarajan MK,
Aiyalu R, Sreedhar R, et al. Nootropic activity of acetaminophen against
colchicine induced cognitive impairment in rats. J Clin Biochem Nutr
;50:241-4.
Sil S, Goswami AR, Dutta G, Ghosh T. Effects of naproxen on immune
responses in a colchicine-induced rat model of Alzheimer’s disease.
Neuroimmunomodulation 2014;21:304-21.
Sil S, Ghosh R, Sanyal M, Guha D, Ghosh T. A comparison of
neurodegeneration linked with neuroinflammation in different
brain areas of rats after intracerebroventricular colchicine injection.
J Immunotoxicol 2015 27:1-10. [Epub ahead of print].
Raghavendra M, Maiti R, Kumar S, Acharya SB. Role of Ocimum
sanctum in the experimental model of Alzheimer’s disease in rats. Int J
Green Pharm 2008;3:6-15.
Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates.
Sydney: Academic Press; 1986.
Yuk DY, Lee YK, Nam SY, Yun YW, Hwang DY, Choi DY, et al.
Reduced anxiety in the mice expressing mutant (N141I) presenilin 2.
J Neurosci Res 2009;87(2):522-31.
Ognibene E, Middei S, Daniele S, Adriani W, Ghirardi O, Caprioli A,
et al. Aspects of spatial memory and behavioral disinhibition in Tg2576
transgenic mice as a model of Alzheimer’s disease. Behav Brain Res
;156(2):225-32.
Arendash GW, King DL, Gordon MN, Morgan D, Hatcher JM,
Hope CE, et al. Progressive, age-related behavioral impairments in
transgenic mice carrying both mutant amyloid precursor protein and
presenilin-1 transgenes. Brain Res 2001;891(1-2):42-53.
Lee KW, Lee SH, Kim H, Song JS, Yang SD, Paik SG, et al. Progressive
cognitive impairment and anxiety induction in the absence of plaque
deposition in C57BL/6 inbred mice expressing transgenic amyloid
precursor protein. J Neurosci Res 2004;76(4):572-80.
Lister RG. The use of a plus-maze to measure anxiety in the mouse.
Psychopharmacology (Berl) 1987;92(2):180-5.
Knyazev GG, Savostyanov AN, Levin EA. Uncertainty, anxiety, and
brain oscillations. Neurosci Lett 2005;387(3):121-5.
Ganguly R, Guha D. Alzheimer’s disease and protection by Moringa
oleifera. Ind J Med Res 2008;128:744-51.
Nishimura H, Tanaka M. Effects of alprazolam on anxiety-related
behavior of rats in a modified forced-swim test employing straw
suspension. Pharmacol Biochem Behav 1992;41(2):425-7.
Rauch SL, Shin LM, Wright CI. Neuroimaging studies of amygdala
function in anxiety disorders. Ann N Y Acad Sci 2003;985:389-410.
Engin E, Treit D. The role of hippocampus in anxiety: Intracerebral
infusion studies. Behav Pharmacol 2007;18(5-6):365-74.
Holsboer F. The rationale for corticotropin-releasing hormone receptor
(CRH-R) antagonists to treat depression and anxiety. J Psychiatr Res
;33(3):181-214.
Chiba S, Numakawa T, Ninomiya M, Richards MC, Wakabayashi C,
Kunugi H. Chronic restraint stress causes anxiety- and depressionlike
behaviors,
downregulates
glucocorticoid
receptor
expression,
and
attenuates
glutamate
release
induced
by brain-derived neurotrophic
factor
in
the prefrontal
cortex.
Prog
Neuropsychopharmacol Biol
Psychiatry
;39(3):112-9.
Contarino A, Dellu F, Koob GF, Smith GW, Lee KF, Vale W, et al.
Reduced anxiety-like and cognitive performance in mice lacking the
corticotropin-releasing factor receptor 1. Brain Res 1999;835(1):1-9.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.