Document Type : Original Article

Authors

1 PhD. in Physiology, Department of Physiology, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin , Iran

2 Student of Medicine, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran

Abstract

The aim of present study, was to investigate the therapeutic efficacy of morphine on memory in Healthy and Streptozotocin (STZ) Rat Model of AD.
Methods: In first experiment animals were divided to: Control and Morphine group which were injected with saline and Morphine (5mg/kg, ip.) In the second experiment animals were divided to: control, sham and groups treated with STZ and STZ plus saline or morphine (2 mg/kg.). For induction of AD, STZ (3 mg/kg, 10 μl/injection site) were administered into lateral ventricles. Morphine , were injected for 10days. All rates were trained in the water maze.
Results: our results show that Morphine (5mg/kg) impaired learning in Healthy rats. our results also show that i.c.v. injection of STZ significantly increased escape latency and Swimming distance to find the platform in comparison with the control group (P

Keywords

Main Subjects

[1]. Rai S, Kamat PK, Nath C, Shukla R. A Study on Neuroinflammation and NMDA Receptor Function in Stz (Icv) Induced Memory Impaired Rats. J Neuroimmunol.2013; 254(1-2): 1-9.
[2]. Rafii MS, Aisen PS. Recent Developments in Alzheimer's Disease Therapeutics. BMC Med. 2009; 7: 7.
[3]. Price DL, Sisodia SS. Mutant genes in familial Alzheimer's disease and transgenic models. Annu Rev Neurosci.1998;21:479-505.
[4]. Li M, Chen L, Lee DH, Yu LC, Zhang Y. The role of intracellular amyloid beta in Alzheimer's disease. Prog Neurobiol. 2007 Oct;83(3):131-9. Epub 2007 Aug 19.
[5]. Williams RJ, Spencer JP. Flavonoids, Cognition, and Dementia: Actions, Mechanisms, and Potential Therapeutic Utility for Alzheimer Disease. Free Radic Biol Med. 2012; 52(1): 35-45.
[6]. Ling L. Streptozocin. free radical and radiation biology program. 2001; 22(777): 1-10.
[7]. Darbandi N, Hezavehi M, Ghadimi F, Noori M. The Effect Of Hydroalcoholic Extract Of Cornus Mas L. Seed On Memory Retention And Some Serum Parameters In Alzheimer Induced Male Mice. Journal of Cell & Tissue.2015;6(3): 269-280.
[8]. Zhang Y, Chen Q, Yu LC. Morphine: a protective or destructive role in neurons? Neuroscientist. 2008 Dec;14(6):561-70.
[9]. Bao G, Kang L, Li H, Li Y, Pu L, Xia P, et al. Morphine and heroin differentially modulate in vivo hippocampal LTP in
opiate-dependent rat. Neuropsychopharmacology. 2007 Aug;32(8):1738-49.
[10]. Salmanzadeh F, Fathollahi Y, Semnanian S, Shafizadeh M.Dependence on morphine impairs the induction of longterm
potentiation in the CA1 region of rat hippocampal slices. Brain Res. 2003 Mar 7;965(1-2):108-13.
[11]. Spain JW, Newsom GC. Chronic opioids impair acquisition of both radial maze and Y-maze choice escape.
Psychopharmacology (Berl). 1991;105(1):101-6.
[12]. Zarrindast MR, Ardjmand A, Rezayof A, Ahmadi S. The time profile of morphine effect on different phases of
inhibitory avoidance memory in rat. Arch Iran Med. 2013 Jan;16(1):34-7.
[13]. Zhou Q, Krebs JF, Snipas SJ, Price A, Alnemri ES, Tomaselli KJ, et al. Interaction of the baculovirus anti-apoptotic
protein p35 with caspases. Specificity, kinetics, and characterization of the caspase/p35 complex.Biochemistry. 1998 Jul 28;37(30):10757-65. 
[14]. Sanchez-Simon FM, Arenzana FJ, Rodriguez RE. In vivo effects of morphine on neuronal fate and opioid receptor
expression in zebrafish embryos. Eur J Neurosci. 2010 Aug;32(4):550-9.
[15]. Qian L, Tan KS, Wei SJ, Wu HM, Xu Z, Wilson B, et al.Microglia-mediated neurotoxicity is inhibited by morphine through an opioid receptor-independent reduction of NADPH oxidase activity. J Immunol. 2007 Jul 15;179(2):1198-209.
[16]. Zhao P, Huang Y, Zuo Z. Opioid preconditioning induces opioid receptor-dependent delayed neuroprotection
against ischemia in rats. J Neuropathol Exp Neurol. 2006 Oct;65(10):945-52.
[17]. Liu Y, Nie YM, Wu WK. [The effect of PKC activation and Smac release on inhibition of myocardial cell apoptosis by
Sini Decoction]. Zhong Yao Cai. 2008 Nov;31(11):1675-8.[Article in Chinese] 
[18]. Avdoshina V, Biggio F, Palchik G, Campbell LA, Mocchetti I. Morphine induces the release of CCL5 from astrocytes:
potential neuroprotective mechanism against the HIV protein gp120. Glia. 2010 Oct;58(13):1630-9.
[19]. Cui J, Wang Y, Dong Q, Wu S, Xiao X, Hu J, et al. Morphine protects against intracellular amyloid toxicity by inducing
estradiol release and upregulation of Hsp70. J Neurosci.2011 Nov 9;31(45):16227-40.
[20]. Esmaeili MH, Esmaeili MM. Metformin Improves Learning And Memory In Streptozotocin-Induced Rat
Model Of Sporadic Alzheimer’s Disease. Indian Journal of Fundamental and Applied Life Sciences. 2016;6:270-281.
[21]. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates, 3rd edn. San Diego: Academic Press. 1996.
[22]. 22. McGaugh JL. Time-dependent processes in memory storage. Science.1966; 153: 1351 – 1358.
[23]. Zarrindast MR, Hoghooghi V, Rezayof A. Inhibition of morphine induced amnesia in morphine-sensitized mice:
involvement of dorsal hippocampal GABAergic receptors.Neuropharmacology. 2008; 54:569 – 576.
[24]. Zarrindast MR, Askari E, Khalilzadeh A, Nouraei N.Morphine state dependent learning sensitization and interaction with nitric oxide. Pharmacology. 2006; 78: 66 –71.
[25]. Homayoun H, Khavandgar S, Zarrindast MR. Morphine state-dependent learning: interactions with alpha2-adrenoceptors and acute stress. Behav Pharmacol. 2003; 14:41 – 48.
[26]. Ma MX, Chen YM, He J, Zeng T, Wang JH. Effects of morphine and its withdrawal on Y-maze spatial recognition memory in mice. Neuroscience. 2007; 147: 1059 – 1065.
[27]. Castellano C. Effects of morphine and heroin on discrimination learning and consolidation in  ice.Psychopharmacologia. 1975; 42: 235– 242.
[28]. Itoh J, Ukai M, Kameyama T. Dynorphin A-(1-13) potently improves the impairment of spontaneous alternation
performance induced by the mu-selective opioid receptor agonist DAMGO in mice. J Pharmacol Exp Ther. 1994; 269:
15 – 21.
[29]. Ukai M, Lin HP. Endomorphins 1 and 2 induce amnesia via selective modulation of dopamine receptors in mice.
Eur J Pharmacol. 2002; 446: 97 – 101.
[30]. Jafari MR, Zarrindast MR, Djahanguiri B. Influence of cholinergic system modulators on morphine statedependent
memory of passive avoidance in mice. Physiol Behav. 2006; 88: 146 – 151.
[31]. Gang Lu, Qi-Xin Zhou, Shuo Kang, Chronic Morphine Treatment Impaired Hippocampal Long-Term Potentiation and Spatial Memory via Accumulation of Extracellular Adenosine Acting on Adenosine A1 Receptors .The Journal of  euroscience, April 7, 2010 •30(14):5058 –5070
[32]. Zarrindast MR, Rezayof A. Morphine state-dependent learning: sensitization and interactions  ith dopaminereceptors. Eur J Pharmacol 2004; 497: 197-204.
[33]. MC.Namara RK, Skelton RW. Pretraining morphine impairs acquisition and performance in the Morris water
maze: motivation reduction rather than amnesia.Psychobiol; 1991. 19: 313- 320.
[34]. Motamedi F, Ghoshoni M, Ghiafeh Davoodi F, Naghdi N.Comparison of learning and memory in morphine
dependent rats using different behavioral models. Iranian J Pharmaceutical Res 2003; 2: 225-230.
[35]. Pourmotabbed A, Tahmassian M, Fathollahi Y. The Effect of Morphine Dependency on Spatial Learning and  Memory in Male Rat. Physiology and Pharmacology, 9 (2),127-137. Winter 2005[Article in Persian].
[36]. PU L, Bao GB, Xu N j, Ma L, Pei G. Hippocampal long –term potentation is reduced by chronic opiate treatment and can be restored by re-exposure to opiates. J Neurosci 2002; 22: 1914-1921.
[37]. Jang CG, Lee SY, Yan JJ, Song DK, Loh HH, Ho IK.Impaired water maze learning in μ-opioid receptor knockout mice. Mol Brain Res 2003; 117: 68-72.
[38]. Li Z, Wu C F, Pei G, Xu N J. Reversal of morphine induced memory impairment in mice by withdrawal in morris
water maze: possible involvement of cholinergic system.Pharmacol Biochem Behav 2001; 68: 507-513.
[39]. Budziszewska B, Leskiewicz M, Jaworska-Feil L, Lason W.The effect of N-nitro-L-arginine methyl ester on morphineinduced changes in the plasma corticosterone and testosterone levels in mice. Exp Clin Endocrinol Diabetes
1999;107:75±9.
[40]. Roozendaal B. Glucocorticoids and regulation of memory consolidation. Psychonoroendocrinol; 2000; 25:213-238.
[41]. Bianchi E, Menicacci C, Ghelardini C.Dual effect of morphine in long-term social memory in rat. Br J Pharmacol. 2013 Apr;168(8):1786-93
[42]. Kawano T , Takahashi T, Iwata H, Morikawa A. Effects of ketoprofen for prevention of postoperative cognitive
dysfunction in agedrats, J. Anesth. 28 (2014) 932–936.[43]. Fanjun M, Junfa L, Bingxi Z, Fang J. nPKCepsilon and
NMDA receptors participate in neuroprotection induced by morphine pretreatment. J Neurosurg Anesthesiol. 2006
Apr;18(2):119-24