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1、NIHPublicAccessAuthorManuscriptNeuropharmacology.Authormanuscript;availableinPMC2009March1.NIH-PAAuthorManuscriptPublishedinfinaleditedformas:NIH-PAAuthorManuscriptNIH-PAAuthorManuscriptNeuropharmacology.2008March;54(3):577±587.doi:10.1016/j.neuropharm.2007
2、.11.002.InvolvementofAMPAReceptorsintheAntidepressant-LikeEffectsofLithiumintheMouseTailSuspensionTestandForcedSwimTestToddD.Gould1,2,*,KelleyC.O’Donnell1,3,EliotR.Dow1,4,JingDu1,GuangChen1,andHusseiniK.Manji11LaboratoryofMolecularPathophysiologyandExperime
3、ntalTherapeutics,NationalInstituteofMentalHealth,NationalInstitutesofHealthAbstractInadditiontoitsclinicalantimaniceffects,lithiumalsohasefficacyinthetreatmentofdepression.However,themechanismbywhichlithiumexertsitsantidepressanteffectsisunclear.Ourobjectiv
4、ewastofurthercharacterizetheeffectsofperipheralandcentraladministrationoflithiuminmousemodelsofantidepressantefficacyaswellastoinvestigatetheroleofalpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid(AMPA)receptorsinthesebehaviors.Weutilizedthemouseforc
5、edswimtest(FST)andtailsuspensiontest(TST),intracerebroventricular(ICV)lithiumadministration,AMPAreceptorinhibitors,andBS3crosslinkingfollowedbywesternblot.Bothshort-andlong-termadministrationoflithiumresultedinrobustantidepressant-likeeffectsinthemouseFSTan
6、dTST.UsingICVadministrationoflithium,weshowthattheseeffectsareduetoactionsoflithiumonthebrain,ratherthantoperipheraleffectsofthedrug.BothICVandrodentchow(0.4%LiCl)administrationparadigmsresultedinbrainlithiumconcentrationswithinthehumantherapeuticrange.Thee
7、ffectsoflithiumtodecreaseimmobilityintheFSTandTSTwereblockedbyadministrationofAMPAreceptorinhibitors.Additionally,administrationoflithiumincreasedthecellsurfaceexpressionofGluR1andGluR2inthemousehippocampus.Collectively,thesedatashowthatlithiumexertscentral
8、lymediatedantidepressant-likeeffectsinthemouseFSTandTSTthatrequireAMPAreceptoractivation.LithiummayexertitsantidepressanteffectsinhumansthroughAMPAreceptors,thusfurthersupportingaroleoftargetingAMPArec
