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  • 1 Mashhad University of Medical Sciences Department of Physiology, School of Medicine Mashhad Iran
  • 2 Isfahan University of Medical Sciences Department of Physiology, School of Medicine Isfahan Iran
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The role of ovarian hormones, nitric oxide, and their interaction on learning and memory has been widely investigated. The present study was carried out to evaluate the effect of Acute (A) and Chronic (C) L-Arginine (L-Arg) administration on learning and memory in ovariectomized (OVx) rats. Forty-five rats were divided into six groups: 1) sham, 2) OVx, 3) sham-L-Arg-A, 4) OVx-L-Arg-A, 5) sham-L-Arg-C, 6) OVx-L-Arg-C. The animals of sham-L-Arg-A and OVx-L-Arg-A were acutely treated with 500 mg/kg of L-Arg during 5 test days. Sham-L-Arg-C and OVx-L-Arg-C chronically received 500 mg/kg/day of L-Arg during 8 weeks before 5 test days. The animals in sham and OVx groups received 1 ml/kg saline instead of L-Arg. At the end of the experiment, the animals were tested in Morris water maze and the escape latency and traveled path to reach the platform were compared between groups. Results showed that the escape latency and traveled path in OVx group were significantly higher than in sham group ( p <0.05). The animals in OVx-L-Arg-A group had significantly lower traveled path length and escape latency compared to OVx group ( p <0.001). Chronic treatment by L-Arg had no significant effect on learning and memory in OVx and sham-operated animals. It seems that L-Arg has a role in Morris water maze tasks disturbances in OVx rats but it needs to be further investigated.

  • Alaei H, Hosseini M: Angiotensin converting enzyme inhibitor captopril modifies conditioned place preference induced by morphine and morphine withdrawal signs in rats. Pathophysiology 14(1), 55–60 (2007)

    Hosseini M. , 'Angiotensin converting enzyme inhibitor captopril modifies conditioned place preference induced by morphine and morphine withdrawal signs in rats ' (2007 ) 14 Pathophysiology : 55 -60.

    • Search Google Scholar
  • Alaei H, Moloudi R, Sarkaki AR, Azizi-Malekabadi H, Hanninen O: Daily running promotes spatial learning and memory in rats. Pathophysiology 14(2), 105–108 (2007)

    Hanninen O. , 'Daily running promotes spatial learning and memory in rats ' (2007 ) 14 Pathophysiology : 105 -108.

    • Search Google Scholar
  • Bijhme GA, Bon C, Stutzmann JM, Doble A, Blanchard JC: Possible involvement of nitric oxide in long-term potentiation. Europ. J. of Pharmacol. 199, 379–381 (1991)

    Blanchard J.C. , 'Possible involvement of nitric oxide in long-term potentiation ' (1991 ) 199 Europ. J. of Pharmacol. : 379 -381.

    • Search Google Scholar
  • Blokland A, de Vente J, Prickaerts J, Honig W, Markerink-van Ittersum M, Steinbusch H: Local inhibition of hippocampal nitric oxide synthase does not impair place learning in the Morris water escape task in rats. European Journal of Neuroscience 11(1) 223–232 (1999)

    Steinbusch H. , 'Local inhibition of hippocampal nitric oxide synthase does not impair place learning in the Morris water escape task in rats ' (1999 ) 11 European Journal of Neuroscience : 223 -232.

    • Search Google Scholar
  • Bon CLM, Garthwaite J: On the role of nitric oxide in hippocampal long-term potentiation. J. of Neurosci. 23, 1941–1948 (2003)

    Garthwaite J. , 'On the role of nitric oxide in hippocampal long-term potentiation ' (2003 ) 23 J. of Neurosci. : 1941 -1948.

    • Search Google Scholar
  • Chesler EJ, Juraska JM: Acute administration of estrogen and progesteron impairs the acquisition of the spatial Morris water maze in ovariectomized rats. Hormones and Behavior 38, 234–242 (2000)

    Juraska J.M. , 'Acute administration of estrogen and progesteron impairs the acquisition of the spatial Morris water maze in ovariectomized rats ' (2000 ) 38 Hormones and Behavior : 234 -242.

    • Search Google Scholar
  • Daniel JM, Winsauer, PJ, Brauner IN, Moerschbaecher JM: Estrogen improves response accuracy and attenuates the disruptive effects of delta9-THC in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance. Behavioral Neuroscience 116, 989–998 (2002)

    Moerschbaecher J.M. , 'Estrogen improves response accuracy and attenuates the disruptive effects of delta9-THC in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance ' (2002 ) 116 Behavioral Neuroscience : 989 -998.

    • Search Google Scholar
  • Demady DR, Jianmongkol S, Vuletich JL, Bender AT, Osawa Y: Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme. Molecular Pharmacol. 59(1), 24–29 (2001)

    Osawa Y. , 'Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme ' (2001 ) 59 Molecular Pharmacol : 24 -29.

    • Search Google Scholar
  • Fader AJ, Johnson PE. Dohanich GP: Estrogen improves working but not reference memory and prevents amnestic effects of scopolamine of a radial-arm maze. Pharmacology Biochemistry and Behavior 62, 711–717 (1999)

    Dohanich G.P. , 'Estrogen improves working but not reference memory and prevents amnestic effects of scopolamine of a radial-arm maze ' (1999 ) 62 Pharmacology Biochemistry and Behavior : 711 -717.

    • Search Google Scholar
  • Farr SA, Banks WA, Morley JE: Estradiol potentiates acetylcholine and glutamate-mediated post-trial memory processing in the hippocampus. Brain Research 864, 263–269 (2000)

    Morley J.E. , 'Estradiol potentiates acetylcholine and glutamate-mediated post-trial memory processing in the hippocampus ' (2000 ) 864 Brain Research : 263 -269.

    • Search Google Scholar
  • Farsetti A, Grasselli A, Bacchetti S, Gaetano C, Capogrossi MC: The telomerase tale in vascular aging: Regulation by estrogens and nitric oxide signaling 106(1), 333–337 (2009)

    Capogrossi M.C. , '' (2009 ) 106 The telomerase tale in vascular aging: Regulation by estrogens and nitric oxide signaling : 333 -337.

  • Fuger HN, Cuningha, SG, Rissman EF, Foster TC: Sex differences in the activational effect of ERalpha on spatial learning. Hormones and Behavior 34, 163–170 (1998)

    Foster T.C. , 'Sex differences in the activational effect of ERalpha on spatial learning ' (1998 ) 34 Hormones and Behavior : 163 -170.

    • Search Google Scholar
  • Garthwaite J: Glutamate nitric oxide and cell-cell signalling in the nervous system. Trends Neuroscience 14, 60–67 (1991)

    Garthwaite J. , 'Glutamate nitric oxide and cell-cell signalling in the nervous system ' (1991 ) 14 Trends Neuroscience : 60 -67.

    • Search Google Scholar
  • Gibbs RB: Basal forebrain cholinergic neurons are necessary for estrogen to enhance acquisition of a delayed matching-to-position T-maze task. Hormones and Behavior 42, 245–257 (2005)

    Gibbs R.B. , 'Basal forebrain cholinergic neurons are necessary for estrogen to enhance acquisition of a delayed matching-to-position T-maze task ' (2005 ) 42 Hormones and Behavior : 245 -257.

    • Search Google Scholar
  • Gibbs RB: Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats. Neurobiology of Aging 21, 107–116 (2000)

    Gibbs R.B. , 'Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats ' (2000 ) 21 Neurobiology of Aging : 107 -116.

    • Search Google Scholar
  • Gould E, Woolley CS, Frankfurt M, McEwen BS: Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cell in adulthood. J. of Neurosci. 10, 1286–1291 (1990)

    McEwen B.S. , 'Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cell in adulthood ' (1990 ) 10 J. of Neurosci. : 1286 -1291.

    • Search Google Scholar
  • Grohe C, Kann S, Fink L, Djoufack PC, Paehr M, van Eickels M, Vetter H, Meyer R, Fink KB: 17 Beta-estradiol regulates nNOS and eNOS activity in the hippocampus. Neuroreport 15, 89–93 (2004)

    Fink K.B. , '17 Beta-estradiol regulates nNOS and eNOS activity in the hippocampus ' (2004 ) 15 Neuroreport : 89 -93.

    • Search Google Scholar
  • Ha BJ: Oxidative stress in ovariectomy menopause and role of chondroitin sulfate. Arch. of Pharmacol. Res. 27, 867–872 (2004)

    Ha B.J. , 'Oxidative stress in ovariectomy menopause and role of chondroitin sulfate ' (2004 ) 27 Arch. of Pharmacol. Res. : 867 -872.

    • Search Google Scholar
  • Hara S, Mukai T, Kurosaki K, Mizukami H, Kuriiwa F, Endo T: Different response to exogenous L-Arg in nitric oxide production between hippocampus and striatum of conscious rats: a microdialysis study. Neurosci. Letter 366(3), 302–367 (2004)

    Endo T. , 'Different response to exogenous L-Arg in nitric oxide production between hippocampus and striatum of conscious rats: a microdialysis study ' (2004 ) 366 Neurosci. Letter : 302 -367.

    • Search Google Scholar
  • Healy SD, Braham SR, Braithwaite VA: Spatial working memory in rats: no differences between the sexes. Proceedings, Biological Sciences/The Royal Society, 266, 2303–2308 (1999)

    Braithwaite V.A. , 'Spatial working memory in rats: no differences between the sexes ' (1999 ) 266 Proceedings, Biological Sciences/The Royal Society : 2303 -2308.

    • Search Google Scholar
  • Heinzen EL, Pollack GM: Pharmacokinetics and pharmacodynamics of L-Arg in rats: a model of stimulated neuronal nitric oxide synthesis. Brain Research 989(1), 67–75 (2003)

    Pollack G.M. , 'Pharmacokinetics and pharmacodynamics of L-Arg in rats: a model of stimulated neuronal nitric oxide synthesis ' (2003 ) 989 Brain Research : 67 -75.

    • Search Google Scholar
  • Herlitz A, Thilers P, Habib R: Endogenous estrogen is not associated with cognitive performance before, during, or after menopause. Menopause 14(3), 425–431 (2007)

    Habib R. , 'Endogenous estrogen is not associated with cognitive performance before, during, or after menopause ' (2007 ) 14 Menopause : 425 -431.

    • Search Google Scholar
  • Hishikawa K, Nakaki T, Marumo T, Suzuki H, Kato R, Saruta T: Upregulation of nitric oxide synthase by estradiol in human aortic endothelial cells. FEBS Letters 360, 291–293 (1995)

    Saruta T. , 'Upregulation of nitric oxide synthase by estradiol in human aortic endothelial cells ' (1995 ) 360 FEBS Letters : 291 -293.

    • Search Google Scholar
  • Holschneider DP, Kumazawa T, Chen K, Shih JC: Tissue-specific effects of estrogen on monoamine oxidase A and B in the rat. Life Science 63, 155–160 (1998)

    Shih J.C. , 'Tissue-specific effects of estrogen on monoamine oxidase A and B in the rat ' (1998 ) 63 Life Science : 155 -160.

    • Search Google Scholar
  • Hosseini M, Sadeghnia HR, Salehabadi S, Alavi H, Gorji Ali: The effect of L-arginine and L-NAME on pentylenetetrazole induced seizures in ovariectomized rats, an in vivo study. Seizure 18, 695–698 (2009)

    Gorji A. , 'The effect of L-arginine and L-NAME on pentylenetetrazole induced seizures in ovariectomized rats, an in vivo study ' (2009 ) 18 Seizure : 695 -698.

    • Search Google Scholar
  • Kopf SR, Benton RS, Kalfin R, Giovannini MG, Pepeu G NO synthesis inhibition decreases cortical ACh release and impairs retention of a conditioned response. Brain Research 894, 141–144 (2001)

    Pepeu G. , 'NO synthesis inhibition decreases cortical ACh release and impairs retention of a conditioned response ' (2001 ) 894 Brain Research : 141 -144.

    • Search Google Scholar
  • Kuiper MA, Visser JJ, Scheltens P, Wolters EC: Decreased cerebral fluid nitrate levels in Parkinson’s disease, Alzheimer’s disease and multiple system atrophy patients. J. Neurol. Sci. 121(1), 46–49 (1994)

    Wolters E.C. , 'Decreased cerebral fluid nitrate levels in Parkinson’s disease, Alzheimer’s disease and multiple system atrophy patients ' (1994 ) 121 J. Neurol. Sci. : 46 -49.

    • Search Google Scholar
  • Law A, O’Donnell J, Gauthier S, Quirion R: Neuronal and inducible nitric oxide synthase expressions and activities in the hippocampi and cortices of young, adult and aged cognitively unimpaired, and impaired Long-Evans rats. Neuroscience 112(2), 267–275 (2002)

    Quirion R. , 'Neuronal and inducible nitric oxide synthase expressions and activities in the hippocampi and cortices of young, adult and aged cognitively unimpaired, and impaired Long-Evans rats ' (2002 ) 112 Neuroscience : 267 -275.

    • Search Google Scholar
  • Leuner B, Mendolia-Loffredo S, Shors T: High levels of estrogen enhance associative memory formation in OVX females. Psychoneuroendocrinology 29(7), 883–890 (2004)

    Shors T. , 'High levels of estrogen enhance associative memory formation in OVX females ' (2004 ) 29 Psychoneuroendocrinology : 883 -890.

    • Search Google Scholar
  • López-Jaramillo, P, Terán E: Improvement in functions of the central nervous system by estrogen replacement therapy might be related with an increased nitric oxide production. Endothelium 6(4), 263–266 (1999)

    Terán E. , 'Improvement in functions of the central nervous system by estrogen replacement therapy might be related with an increased nitric oxide production ' (1999 ) 6 Endothelium : 263 -266.

    • Search Google Scholar
  • Luine VN: Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats. Experimental Neurology 89, 484–490 (1985)

    Luine V.N. , 'Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats ' (1985 ) 89 Experimental Neurology : 484 -490.

    • Search Google Scholar
  • Luine V, Park D, Joh T, Reis D, McEwen B: Immunochemical demonstration of increased choline acetyltransferase concentration in rat preoptic area after estradiol administration. Brain Research 191, 273–277 (1980)

    McEwen B. , 'Immunochemical demonstration of increased choline acetyltransferase concentration in rat preoptic area after estradiol administration ' (1980 ) 191 Brain Research : 273 -277.

    • Search Google Scholar
  • Majlessi N, Choopani S, Bozorgmehr T, Azizi Z: Involvement of hippocampal nitric oxide in spatial learning in the rat. Neurobiology of Learning and Memory 90(2), 413–419 (2008)

    Azizi Z. , 'Involvement of hippocampal nitric oxide in spatial learning in the rat ' (2008 ) 90 Neurobiology of Learning and Memory : 413 -419.

    • Search Google Scholar
  • Monteiro SC, Matté C, Bavaresco CS, Netto CA, Wyse AT: Vitamins E and C pretreatment prevents ovariectomy-induced memory deficits in water maze. Neurobiology of Learning and Memory 84, 192–199 (2005)

    Wyse A.T. , 'Vitamins E and C pretreatment prevents ovariectomy-induced memory deficits in water maze ' (2005 ) 84 Neurobiology of Learning and Memory : 192 -199.

    • Search Google Scholar
  • Nematbakhsh M, Khazaei M: The effect of estrogen on serum nitric oxide concentrations in normotensive and DOCA Salt hypertensive ovariectomized rats. Clinica Chimica Acta 344(1–2), 53–57 (2004)

    Khazaei M. , 'The effect of estrogen on serum nitric oxide concentrations in normotensive and DOCA Salt hypertensive ovariectomized rats ' (2004 ) 344 Clinica Chimica Acta : 53 -57.

    • Search Google Scholar
  • Noda Y, Yamada K, Nabeshima T: Role of the nitric oxide in the effect of aging on spatial memory in rats. Behavioral Brain Research 83(1/2), 153–158 (1997)

    Nabeshima T. , 'Role of the nitric oxide in the effect of aging on spatial memory in rats ' (1997 ) 83 Behavioral Brain Research : 153 -158.

    • Search Google Scholar
  • O’Dell TJ, Hawkins RD, Kandel ER, Arancio O: Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. The Proceedings of the National Academy of Sciences Online (US) 88 11285–11289 (1991)

    Arancio O. , 'Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger ' (1991 ) 88 The Proceedings of the National Academy of Sciences Online (US) : 11285 -11289.

    • Search Google Scholar
  • Okamura H, Yokosuka M, Hayashi S: Estrogenic induction of NADPH diaphorase activity in the preoptic neurons containing estrogen receptor immunoreactivity in the female rat. J. of Neuroendocrinol. 6, 597–601 (1994)

    Hayashi S. , 'Estrogenic induction of NADPH diaphorase activity in the preoptic neurons containing estrogen receptor immunoreactivity in the female rat ' (1994 ) 6 J. of Neuroendocrinol. : 597 -601.

    • Search Google Scholar
  • Ping SE, Trieu J, Wlodek ME, Barrett GL: Effects of estrogen on basal forebrain cholinergic neurons and spatial learning. J. of Neurosci. Res. 86(7), 1588–1598 (2008)

    Barrett G.L. , 'Effects of estrogen on basal forebrain cholinergic neurons and spatial learning ' (2008 ) 86 J. of Neurosci. Res. : 1588 -1598.

    • Search Google Scholar
  • Plech A, Klimkiewicz T, Maksym B: Effect of L-Arg on memory in rats. Polish J. of Pharmacol. 55, 987–992 (2003)

    Maksym B. , 'Effect of L-Arg on memory in rats ' (2003 ) 55 Polish J. of Pharmacol. : 987 -992.

    • Search Google Scholar
  • Prast H, Philippu A: Nitric oxide as modulator of neuronal function. Progress in Neurobiology 64, 51–68 (2001)

    Philippu A. , 'Nitric oxide as modulator of neuronal function ' (2001 ) 64 Progress in Neurobiology : 51 -68.

    • Search Google Scholar
  • Raasch W, Schafer U, Chun J, Dominiak P: Biological significance of agmatine an endogenous ligand at imidazoline binding sites. Brit. J. of Pharmacol. 133, 755–780 (2001)

    Dominiak P. , 'Biological significance of agmatine an endogenous ligand at imidazoline binding sites ' (2001 ) 133 Brit. J. of Pharmacol. : 755 -780.

    • Search Google Scholar
  • Reis DJ, Regunathan S: Is agmatine a novel neurotransmitter in brain? Trends in Pharmacological Sciences 21, 187–193 (2000)

    Regunathan S. , 'Is agmatine a novel neurotransmitter in brain? ' (2000 ) 21 Trends in Pharmacological Sciences : 187 -193.

    • Search Google Scholar
  • Russell KS, Haynes MP, Caulin-Glaser T, Rosneck J, Sessa WC, Bender JR: Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells. Effects on calcium sensitivity and NO release. J. of Biol. Chem. 275, 5026–5030 (2000)

    Bender J.R. , 'Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells. Effects on calcium sensitivity and NO release ' (2000 ) 275 J. of Biol. Chem. : 5026 -5030.

    • Search Google Scholar
  • Sato T, Teramoto T, Tanaka K, Ohnishi Y, Irifune M, Nishikawa T: Effects of ovariectomy and calcium deficiency on learning and memory of eight-arm radial maze in middle-aged female rats. Behavioral Brain Research 142, 207–216 (2003)

    Nishikawa T. , 'Effects of ovariectomy and calcium deficiency on learning and memory of eight-arm radial maze in middle-aged female rats ' (2003 ) 142 Behavioral Brain Research : 207 -216.

    • Search Google Scholar
  • Savonenko A, Markowska AL: The cognitive effects of ovariectomy and estrogen replacement are modulated by aging. Neuroscience 119, 821–830 (2003)

    Markowska A.L. , 'The cognitive effects of ovariectomy and estrogen replacement are modulated by aging ' (2003 ) 119 Neuroscience : 821 -830.

    • Search Google Scholar
  • Schuman EM, Madison DV: A requirement for the intercellular messenger nitric oxide in long-term potentiation. Science 254, 1503–1506 (1991)

    Madison D.V. , 'A requirement for the intercellular messenger nitric oxide in long-term potentiation ' (1991 ) 254 Science : 1503 -1506.

    • Search Google Scholar
  • Singh M, Meyer EM, Millard WJ, Simpkins JW: Ovarian steroid deprivation results in a reversible learning impairmentand compromised cholinergic function in female Sprague-Dawley rats. Brain Research 644, 305–312 (1994)

    Simpkins J.W. , 'Ovarian steroid deprivation results in a reversible learning impairmentand compromised cholinergic function in female Sprague-Dawley rats ' (1994 ) 644 Brain Research : 305 -312.

    • Search Google Scholar
  • Stefano GB, Prevot V, Beauvillain JC, Cadet P, Fimiani C, Welters I. Fricchione GL, Breton C, Lassalle P, Salzet M, Bilfinger TV: Cell surface estrogen receptors mediate calcium-dependent nitric oxide release in human endothelia. Circulation 101, 1594–1597 (2000)

    Bilfinger T.V. , 'Cell surface estrogen receptors mediate calcium-dependent nitric oxide release in human endothelia ' (2000 ) 101 Circulation : 1594 -1597.

    • Search Google Scholar
  • Warren SG, Humphreys AG, Juraska JM, Greenough WT: LTP varies across the estrous cycle: enhanced synaptic plasticity in proestrous rats. Brain Research 703, 26–30 (1995)

    Greenough W.T. , 'LTP varies across the estrous cycle: enhanced synaptic plasticity in proestrous rats ' (1995 ) 703 Brain Research : 26 -30.

    • Search Google Scholar
  • Yamada K, Nabeshima T: Changes in NMDA receptor/nitric oxide signalling pathway in the brain with aging. Microscopy Research and Technique 43(1), 68–74 (1997)

    Nabeshima T. , 'Changes in NMDA receptor/nitric oxide signalling pathway in the brain with aging ' (1997 ) 43 Microscopy Research and Technique : 68 -74.

    • Search Google Scholar
  • Yildirim M, Marangoz C: Effects of nitric oxide on passive avoidance learning in rats. Internat. J. of Neurosci. 114, 597–606 (2004)

    Marangoz C. , 'Effects of nitric oxide on passive avoidance learning in rats. Internat ' (2004 ) 114 J. of Neurosci. : 597 -606.

    • Search Google Scholar
  • Yildiz Akar F, Ulak G, Tanyeri P, Erden F, Utkan T, Gacar N: 7-Nitroindazole, a neuronal nitric oxide synthase inhibitor, impairs passive-avoidance and elevated plus-maze memory performance in rats. Pharmacology, Biochemistry and Behavior 87(4), 434–443 (2007)

    Gacar N. , '7-Nitroindazole, a neuronal nitric oxide synthase inhibitor, impairs passive-avoidance and elevated plus-maze memory performance in rats ' (2007 ) 87 Pharmacology, Biochemistry and Behavior : 434 -443.

    • Search Google Scholar
  • Zou LB, Yamada K, Tanaka T, Kameyama T, Nabeshima T: Nitric oxide synthase inhibitors impair reference memory formation in a radial arm maze task in rats. Neuropharmacology 37(3), 323–330 (1998)

    Nabeshima T. , 'Nitric oxide synthase inhibitors impair reference memory formation in a radial arm maze task in rats ' (1998 ) 37 Neuropharmacology : 323 -330.

    • Search Google Scholar

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