title: Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression.
abstract: Depression is a highly prevalent and recurrent neuropsychiatric disorder associated with alterations in emotional and cognitive domains. Neuroplastic phenomena are increasingly considered central to the etiopathogenesis of and recovery from depression. Nevertheless, a high number of remitted patients experience recurrent episodes of depression, remaining unclear how previous episodes impact on behavior and neuroplasticity and/or whether modulation of neuroplasticity is important to prevent recurrent depression. Through re-exposure to an unpredictable chronic mild stress protocol in rats, we observed the re-appearance of emotional and cognitive deficits. Furthermore, treatment with the antidepressants fluoxetine and imipramine was effective to promote sustained reversion of a depressive-like phenotype; however, their differential impact on adult hippocampal neuroplasticity triggered a distinct response to stress re-exposure: while imipramine re-established hippocampal neurogenesis and neuronal dendritic arborization contributing to resilience to recurrent depressive-like behavior, stress re-exposure in fluoxetine-treated animals resulted in an overproduction of adult-born neurons along with neuronal atrophy of granule neurons, accounting for an increased susceptibility to recurrent behavioral changes typical of depression. Strikingly, cell proliferation arrest compromised the behavior resilience induced by imipramine and buffered the susceptibility to recurrent behavioral changes promoted by fluoxetine. This study shows that previous exposure to a depressive-like episode impacts on the behavioral and neuroanatomical changes triggered by subsequent re-exposure to similar experimental conditions and reveals that the proper control of adult hippocampal neuroplasticity triggered by antidepressants is essential to counteract recurrent depressive-like episodes.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: N D
authors.initials: ND
authors.lastname: Alves
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: J S
authors.initials: JS
authors.lastname: Correia
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Patrício
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Mateus-Pinheiro
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: A R
authors.initials: AR
authors.lastname: Machado-Santos
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: E
authors.initials: E
authors.lastname: Loureiro-Campos
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Morais
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: J M
authors.initials: JM
authors.lastname: Bessa
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: N
authors.initials: N
authors.lastname: Sousa
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Pinto
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003866:Depressive Disorder; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D013315:Stress, Psychological
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D007099:Imipramine