Amin S.N.El-Aidi A.A.Ali M.M.Attia Y.M.Rashed L.A.Department of Medical PhysiologyKasr Al Ainy Faculty of MedicineCairo UniversityAl ManyalCairo11451Egypt; Faculty of PharmacyMSA UniversityCairoEgypt; Department of BiochemistryFaculty of MedicineCairo UniversityCairoEgypt2020-01-092020-01-09201515351084https://doi.org/10.1007/s12017-015-8343-0PubMed ID 25680935https://t.ly/LXMPWScopusStress is any condition that impairs the balance of the organism physiologically or psychologically. The response to stress involves several neurohormonal consequences. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its release is increased by stress that predisposes to excitotoxicity in the brain. Memantine is an uncompetitive N-methyl D-aspartate glutamatergic receptors antagonist and has shown beneficial effect on cognitive function especially in Alzheimer�s disease. The aim of the work was to investigate memantine effect on memory and behavior in animal models of acute and repeated restraint stress with the evaluation of serum markers of stress and the expression of hippocampal markers of synaptic plasticity. Forty-two male rats were divided into seven groups (six rats/group): control, acute restraint stress, acute restraint stress with Memantine, repeated restraint stress, repeated restraint stress with Memantine and Memantine groups (two subgroups as positive control). Spatial working memory and behavior were assessed by performance in Y-maze. We evaluated serum cortisol, tumor necrotic factor, interleukin-6 and hippocampal expression of brain-derived neurotrophic factor, synaptophysin and calcium-/calmodulin-dependent protein kinase II. Our results revealed that Memantine improved spatial working memory in repeated stress, decreased serum level of stress markers and modified the hippocampal synaptic plasticity markers in both patterns of stress exposure; in ARS, Memantine upregulated the expression of synaptophysin and brain-derived neurotrophic factor and downregulated the expression of calcium-/calmodulin-dependent protein kinase II, and in repeated restraint stress, it upregulated the expression of synaptophysin and downregulated calcium-/calmodulin-dependent protein kinase II expression. � 2015, Springer Science+Business Media New York.EnglishBehaviorMemantineMemoryRestraintSynaptic plasticityamino acid receptor blocking agentbiological markerbrain derived neurotrophic factorcalcium calmodulin dependent protein kinase IIhydrocortisoneinterleukin 6memantinenerve proteinneuroprotective agentsynaptophysinSyp protein, rattumor necrosis factor alphaacute diseaseadverse effectsanimalanimal behavioranxietybiosynthesisbloodcatalepsychemistrydrug effectsdrug therapyetiologyexercisegene expression regulationgeneticsgroominghippocampusmalemaze testmental stressnerve cell plasticitynervous system developmentpathophysiologyphysiological stressphysiologypreclinical studyratspatial memoryWistar ratAcute DiseaseAnimalsAnxietyBehavior, AnimalBiomarkersBrain-Derived Neurotrophic FactorCalcium-Calmodulin-Dependent Protein Kinase Type 2Drug Evaluation, PreclinicalExcitatory Amino Acid AntagonistsFreezing Reaction, CatalepticGene Expression RegulationGroomingHippocampusHydrocortisoneInterleukin-6MaleMaze LearningMemantineNerve Tissue ProteinsNeurogenesisNeuronal PlasticityNeuroprotective AgentsRatsRats, WistarRestraint, PhysicalSpatial MemoryStress, PhysiologicalStress, PsychologicalSynaptophysinTumor Necrosis Factor-alphaArticlehttps://doi.org/10.1007/s12017-015-8343-0PubMed ID 25680935