Role of the Amygdala in Antidepressant Effects on Hippocampal Cell Proliferation and Survival and on Depression-like Behavior in the Rat 英文参考文献.docVIP
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Role of the Amygdala in Antidepressant Effects on Hippocampal Cell Proliferation and Survival and on Depression-like Behavior in the Rat 英文参考文献
RoleoftheAmygdalainAntidepressantEffectson
HippocampalCellProliferationandSurvivalandon
Depression-likeBehaviorintheRat
JorgeE.Castro,EmilioVarea,CristinaMa′rquez,MariaIsabelCordero,GuillaumePoirier,CarmenSandi*
LaboratoryofBehavioralGenetics,BrainMindInstitute,E′colePolytechniqueFe′de′rale deLausanne(EPFL),Lausanne,Switzerland
Abstract
The stimulation of adult hippocampal neurogenesis by antidepressants has been associated with multiple molecular
pathways, but the potential influence exerted by other brain areas has received much less attention. The basolateral
complexoftheamygdala(BLA),aregioninvolvedinanxietyandasiteofactionofantidepressants,hasbeenimplicatedin
both basal and stress-induced changes in neural plasticity in the dentate gyrus. We investigated here whether the BLA
modulatestheeffectsoftheSSRIantidepressantfluoxetineonhippocampalcellproliferationandsurvivalinrelationtoa
behavioralindexofdepression-likebehavior(forcedswimtest).WeusedalesionapproachtargetingtheBLAalongwitha
chronictreatmentwithfluoxetine,andmonitoredbasalanxietylevelsgiventheimportantroleofthisbehavioraltraitinthe
progressofdepression.ChronicfluoxetinetreatmenthadapositiveeffectonhippocampalcellsurvivalonlywhentheBLA
waslesioned.Anxietywasrelatedtohippocampalcellsurvivalinoppositewaysinsham-andBLA-lesionedanimals(i.e.,
negativelyinsham-andpositivelyinBLA-lesionedanimals).BothBLAlesionsandlowanxietywerecriticalfactorstoenable
anegativerelationshipbetweencellproliferationanddepression-likebehavior.Therefore,ourstudyhighlightsaroleforthe
amygdala on fluoxetine-stimulated cell survival and on the establishment of a link between cell proliferation and
depression-likebehavior.ItalsorevealsanimportantmodulatoryroleforanxietyoncellproliferationinvolvingbothBLA-
dependent and –independent mechanisms. Our findings underscore the amygdala as a potential target to modulate
antidepressants’actioninhippocampalneurogenesisandintheirlinktodepression-likebehaviors.
Citation:CastroJE,VareaE,Ma′rqu
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