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01.06.2012 | Original Paper

Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats

verfasst von: Gislaine Z. Réus, Helena M. Abelaira, Roberto B. Stringari, Gabriel R. Fries, Flávio Kapczinski, João Quevedo

Erschienen in: Metabolic Brain Disease | Ausgabe 2/2012

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Abstract

Memantine is a N-methyl-D-aspartate (NMDA) receptor antagonist and several studies have pointed to the NMDA receptor antagonists as a potential therapeutic target for the treatment of depression. The present study was aimed to evaluate the behavioral and physiological effects of administration of memantine in rats exposed to the chronic mild stress (CMS) model. To this aim, after 40 days of exposure to CMS procedure, rats were treated with memantine (20 mg/kg) for 7 days. In this study, sweet food consumption, adrenal gland weight, corticosterone levels, and brain-derived-neurotrophic factor (BDNF) protein levels in the prefrontal cortex, hippocampus and amygdala were assessed. Our results demonstrated that chronic stressful situations induced anhedonia, hypertrophy of adrenal gland weight, and an increase of corticosterone levels in rats, but did not alter BDNF protein levels in the rat brain. Memantine treatment reversed anhedonia and the increase of adrenal gland weight, normalized corticosterone levels and increased BDNF protein levels in the prefrontal cortex in stressed rats. Finally, these findings further support the hypothesis that NMDA receptor antagonists such as memantine could be helpful in the pharmacological treatment of depression.

Alboni SC, Benatti G, Capone D, Corsini F, Caggia F, Tascedda J, Mendlewicz N, Brunello (2010) Time-dependent effects of escitalopram on brain derived Neurotrophic factor (BDNF) and neuroplasticity related targets in the central nervous system of rats. Eur J Pharmacol 643:180–187PubMedCrossRef

Allaman I, Papp M, Kraftsik R, Fiumelli H, Magistretti PJ, Martin JL (2008) Expression of brain-derived Neurotrophic factor is not modulated by chronic mild stress in the rat hippocampus and amygdale. Pharmacol Report 60:1001–1007

Almeida RC, Felisbino CS, López MG, Rodrigues ALS, Gabilan NH (2006) Evidence for the involvement of l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of memantine in mice. Behav Brain Res 168:318–322PubMedCrossRef

Altar CA (1999) Neurotrophins and depression. Trends Pharmaco Sci 20:59–61CrossRef

Berman RB, Cappielo A, Anand A, Oren DA, George RH, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351–354PubMedCrossRef

Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ (2006) Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311:864–868PubMedCrossRef

Bylund DB, Reed AL (2009) Childhood and adolescent depression: why do children and adults respond differently to antidepressant drugs? J Psychopharmacol 23:295–304CrossRef

Drevets WC (2003) Neuroimaging abnormalities in the amygdala in mood disorders. Ann NY Acad Sci 985:420–444PubMedCrossRef

Feier G, Valvassori SS, Rezin GT, Búrigo M, Streck EL, Kapczinski F, Quevedo J (2011) Creatine kinase levels in patients with bipolar disorder: depressive, manic, and euthymic phases. Rev Bras Psiquiatr 33:171–175PubMed

Ferguson JM, Shingleton RN (2007) An open-label, flexible-dose study of memantine in major depressive disorder. Clin Neuropharmacol 30:136–144PubMedCrossRef

Fortunato JJ, Réus GZ, Kirsch TR, Stringari RB, Fries GR, Kapczinski F, Hallak JE, Zuardi AW, Crippa JA, Quevedo J (2010) Effects of beta-carboline harmine on behavioral and physiological parameters observed in the chronic mild stress model: further evidence of antidepressant properties. Brain Res Bull 81:491–496PubMedCrossRef

Frey BN, Andreazza AC, Ceresér KMM, Martins MR, Valvassori SS, Réus GZ, Quevedo J, Kapczinski F (2006) Effects of mood stabilizers on hippocampus BDNF levels in an animal model of mania. Life Sci 79:281–286PubMedCrossRef

Gamaro GD, Manoli LP, Torres IL, Silveira R, Dalmaz C (2003) Effects stress on feeding behavior and on monoamine levels in structures. Neurochem Int 42:107–114PubMedCrossRef

Garcia LB, Comim CM, Valvassori SS, Réus GZ, Barbosa LM, Andreazza AC, Stertz L, Fries GR, Gavioli EC, Kapczinski F, Quevedo J (2008a) Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatr 32:140–144CrossRef

Garcia LB, Comim CM, Valvassori SS, Réus GZ, Barbosa LM, Andreazza AC, Stertz L, Fries GR, Gavioli EC, Kapczinski F, Quevedo J (2008b) Chronic administration of ketamine elicits antidepressant-like effects in rats without affecting Hippocampal brain-derived Neurotrophic factor protein levels. Basic Clin Pharmacol Toxicol 103:502–506PubMedCrossRef

Garcia LSB, Comim CM, Valvassori SS, Réus GZ, Stertz L, Kapczinski F, Gavioli EC, Quevedo J (2009) Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats. Prog Neuropsychopharmacol Biol Psychiatr 30:450–455CrossRef

Harro J, Tonissaar M, Eller M, Kask A, Oreland L (2001) Chronic variable stress and partial 5-HT denervation by parachloroamphetamine treatment in the rat: effects on behavior and monoamine neurochemistry. Brain Res 899:227–239PubMedCrossRef

Hashimoto K (2009) Emerging role of glutamate in the pathophysiology of major depressive disorder. Brain Res Rev 61:105–123PubMedCrossRef

Hashimoto K (2011) The role of glutamate on the action of antidepressants. Prog Psychopharmacol Biol Psychiatr 35:1558–1568CrossRef

Hashimoto K, Tsukada H, Nishiyama S, Fukumoto D, Kakiuchi T, Shimizu E, Iyo M (2004) Protective effects of N-acetyl-L-cysteine on the reduction of dopamine transporters in the striatum of monkeys treated with methamphetamine. Neuropsychopharmacol 29:2018–2023CrossRef

Jacobs BL, Praag H, Gage FH (2000) Molecular brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry 5:262–269PubMedCrossRef

Jantas D, Szymanska EM, Budziszewska EB, Lason EW (2009) An involvement of BDNF and PI3-K/Akt in the anti-apoptotic effect of memantine on staurosporine-evoked cell death in primary cortical neurons. Apoptosis 14:900–912PubMedCrossRef

Jantas-Skotniczna D, Kajta M, Lason W (2006) Memantine attenuates staurosporine-induced activation of caspase-3 and LDH release in mouse primary neuronal cultures. Brain Res 1069:145–153PubMedCrossRef

Johnson JW, Kotermanski SE (2006) Mechanism of action of memantine. Curr Opin Pharmacol 6:61–67PubMedCrossRef

Karege F, Vaudan G, Schwald M, Perroud N, La Harpe R (2005) Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res Mol Brain Res 136:29–37PubMedCrossRef

Katz RJ, Roth KA, Carroll BJ (1981) Animal models and human depressive disorders. Neurosci Biobehav Rev 5:231–246PubMedCrossRef

Kim JS, Schmid-Burgk W, Claus D, Kornhuber HH (1982) Increased serum glutamate in depressed patients. Arch Psychiatr Nervenkr 23:299–304CrossRef

Konarska M, Stewart RE, McCarty R (1990) Predictability of chronic intermittent stress: effects on sympathetic-adrenal medullary responses of laboratory rat. Behav Neural Biol 53:231–243PubMedCrossRef

Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455:894–902PubMedCrossRef

Lewin GR, Barde YA (1997) Physiology of the neurotrophins. Annu Rev Neurosci 19:215–221

Lindsay RM, Wiegand SJ, Altar CA, DiStefano PS (1994) Neurotrophic factors: from molecule to man. Trends Neurosci 17:182–190PubMedCrossRef

Lipton SA (2004) Paradigm shift in NMDA receptor antagonist drug development: molecular mechanism of uncompetitive inhibition by memantine in the treatment of Alzheimer’s disease and other neurological disorders. J Alzheimer’s Dis 6:61–74

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275PubMed

Lucca G, Comim CM, Valvassori SS, Pereira JG, Stertz L, Gavioli EC, Kapczinski F, Quevedo J (2008) Chronic mild stress paradigm reduces sweet food intake in rats without affecting brain derived Neurotrophic factor protein levels. Curr Neurovasc Res 5:207–213PubMedCrossRef

Lucca G, Comim CM, Valvassori SS, Réus GZ, Vuolo F, Petronilho F, Gavioli EC, Dal-Pizzol F, Quevedo J (2009a) Increased oxidative stress in submitocondrial particles into the brain of rats submitted to the chronic mild stress paradigm. J Psychiatr Res 43:864–869PubMedCrossRef

Lucca G, Comim CM, Valvassori SS, Réus GZ, Vuolo F, Petronilho F, Dal-Pizzol F, Gavioli EC, Quevedo J (2009b) Effects of chronic mild stress on the oxidative parameters in the rat brain. Neurochem Int 54:358–362PubMedCrossRef

Magalhães PV, Dean OM, Bush AI, Copolov DL, Malhi GS, Kohlmann K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Berk M (2011) N-acetylcysteine for major depressive episodes in bipolar disorder. Rev Bras Psiquiatr 33:374–188PubMedCrossRef

Magariños AM, McEwen BS (1995) Stress-induced atrophy of apical dendrites of Hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience 69:89–98PubMedCrossRef

Manji HK, Drevets WC, Charney DS (2001) The cellular neurobiology of depression. Nature Med 7:541–547PubMedCrossRef

Marvanová M, Lakso M, Pirhonen J, Nawa N, Hiroyoki N, Wong G, Castrén E (2001) The neuroprotective agent memantine induces brain-derived Neurotrophic factor and trkb receptor expression in rat brain. Mol Cell Neurosci 18:247–258PubMedCrossRef

Mitani H, Shirayama Y, Yamada T, Maeda K, Ashby CR Jr, Kawahara R (2006) Correlation between plasma levels of glutamate, alanine and serine with severity of depression. Prog Neuropsychopharmacol Biol Psychiatr 30:1155–1158CrossRef

Moghaddam B, Bolinao ML, Stein-Behrens B, Sapolsky R (1994) Glucocorticoids mediate the stress-induced extracellular accumulation of glutamate. Brain Res 655:251–254PubMedCrossRef

Moryl E, Danysz W, Quack G (1993) Potential antidepressive properties of Amantadine, memantine and bifemelane. Pharmacol Toxicol 72:394–397PubMedCrossRef

Namba T, Yabe T, Gonda Y, Ichikawa N, Sanagi T, Arikawa-Hirasawa E, Mochizuki H, Kohsaka S, Uchino S (2010) Pigment epithelium-derived factor up-regulation induced by memantine, an N-methyl-D-aspartate receptor antagonist, is involved in increased proliferation of Hippocampal progenitor cells. Neuroscience 167:372–383PubMedCrossRef

Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia M (2002) Neurobiology of depression. Neuron 34:13–25PubMedCrossRef

O’Connor TM, O’Halloran DJ, Shanahan F (2000) The stress response and the hypothalamic–pituitary–adrenal axis: from molecule to melancholia. Q J Med 93:323–333CrossRef

Parsons CG, Danysz W, Quack G (1999) Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist–a review of preclinical data. Neuropharmacology 38:735–767PubMedCrossRef

Paxinos G, Watson C (1986) The rat brain: stereotaxic coordinates, 2nd edn. Academic, Australia

Pittenger C, Duman R (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33:88–109PubMedCrossRef

Quan MN, Zhang N, Wang YY, Zhang T, Yang Z (2011) Possible antidepressant effects and mechanisms of memantine in behaviors and synaptic plasticity of a depression rat model. Neuroscience 182:88–97PubMedCrossRef

Rammes G, Rupprecht R, Ferrari U, Zieglgansberger W, Parsons CG (2001) The N-methyl-D aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non competitive manner. Neurosci Lett 306:81–84PubMedCrossRef

Rammes G, Danysz W, Parsons CJ (2008) Pharmacodynamics of memantine: an update. Curr Neuropharmacol 6:55–78PubMedCrossRef

Réus GZ, Valvassori SS, Machado RA, Martins MR, Gavioli EC, Quevedo J (2008) Acute treatment with low doses of memantine does not impair aversive, nonassociative and recognition memory in rats. Naunyn Schmiedeberg’s Arch Pharmacol 376:295–300CrossRef

Réus GZ, Stringari RB, Kirshi TR, Fries GR, Kapczinski F, Roesler R, Quevedo J (2010) Neurochemical and behavioural effects of acute and chronic memantine administration in rats: further support for NMDA as a new pharmacological target for the treatment of depression? Brain Res Bull 81:585–589PubMedCrossRef

Rogóz Z, Skuza G, Legutko B (2008) Repeated co-treatment with fluoxetine and Amantadine induces brain-derived Neurotrophic factor gene expression in rats. Pharmacol Rep 60:817–826PubMed

Rogóz Z, Kubera M, Rogóz K, Basta-Kaim A, Budziszewska B (2009) Effect of co-administration of fluoxetine and amantadine on immunoendocrine parameters in rats subjected to a forced swimming test. Pharmacol Rep 61:1050–1060PubMed

Roman A, Rogóz Z, Kubera M, Nawrat D, Nalepa I (2009) Concomitant administration of fluoxetine and Amantadine modulates the activity of peritoneal macrophages of rats subjected to a forced swimming test. Pharmacol Rep 61:1069–1077PubMed

Skolnick P, Popik P, Trullas R (2009) Glutamate-based antidepressants: 20 years on. Trends Pharmacol Sci 30:563–569PubMedCrossRef

Szasz BK, Mike A, Karoly R, Gerevich Z, Illes P, Vizi ES, Kiss JP (2007) Direct inhibitory effect of fluoxetine on N-methyl-D-aspartate receptors in the central nervous system. Biol Psychiatry 62:1303–1309PubMedCrossRef

Vollmayr B, Henn FA (2003) Stress models of depression. Clin Neurosci Res 3:245–251CrossRef

Yamada K, Nabeshima T (2004) Interaction of BDNF/TrkB signaling with NMDA receptor in learning and memory. Drug News Perspect 17:435–438PubMedCrossRef

Zarate CA, Singh JB, Carson PJ, Brutshe NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-d-aspartate antagonist in treatment resistant major depression. Arch Gen Psychiatry 63:856–864PubMedCrossRef

Titel: Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats
verfasst von: Gislaine Z. Réus
Helena M. Abelaira
Roberto B. Stringari
Gabriel R. Fries
Flávio Kapczinski
João Quevedo
Publikationsdatum: 01.06.2012
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 2/2012
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-012-9281-2

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