Blocking Mineralocorticoid Receptors prior to Retrieval Reduces Contextual Fear Memory in Mice 英文参考文献.docVIP

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Blocking Mineralocorticoid Receptors prior to Retrieval Reduces Contextual Fear Memory in Mice 英文参考文献.doc

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Blocking Mineralocorticoid Receptors prior to Retrieval Reduces Contextual Fear Memory in Mice 英文参考文献

BlockingMineralocorticoidReceptorspriortoRetrieval ReducesContextualFearMemoryinMice MingZhou1,MerelKindt2,MarianJoe¨ls1,3,HarmJ.Krugers1* 1Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands, 2Department of Clinical Psychology, UniversityofAmsterdam,Amsterdam,TheNetherlands,3DepartmentofNeuroscienceandPharmacology,RudolfMagnusInstituteofNeuroscience,UniversityMedical CenterUtrecht,Utrecht,TheNetherlands Abstract Background:Corticosteroidhormonesregulateappraisalandconsolidationofinformationviamineralocorticoidreceptors (MRs) and glucocorticoid receptors (GRs) respectively. How activation of these receptors modulates retrieval of fearful informationandthesubsequentexpressionoffearislargelyunknown.WetestedherewhetherblockadeofMRsorGRs duringretrievalalsoaffectssubsequentexpressionoffearmemory. Methodology/PrincipalFindings:Miceweretrainedincontextualortonecuefearconditioningparadigms,bypairingmild foot shocks with a particular context or tone respectively. Twenty-four hours after training, context-conditioned animals werere-exposedtothecontextfor3or30minutes(day2);tone-conditionedanimalswereplacedinadifferentcontextand re-exposedtooneorsixtones.Twenty-fourhours(day3)andonemonthlater,freezingbehaviortotheaversivecontext/ tone was scored again. MR or GR blockade was achieved by giving spironolactone or RU486 subcutaneously one hour beforeretrievalonday2.Spironolactoneadministeredpriortobriefcontextre-exposurereducedfreezingbehaviorduring retrievaland24hourslater,butnotonemonthlater.Administrationofspironolactonewithoutretrievalofthecontextor immediatelyafterretrievalonday2didnotreducefreezingonday3.Re-exposuretothecontextfor30minutesonday2 significantly reduced freezing on day 3 and one month later, but freezing was not further reduced by spironolactone. Administrationofspironolactonepriortotone-cuere-exposureonday2didnotaffectfreezingbehavior.Treatmentwith RU486priortore-exposuredidnotaffectcontextorto