title: Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.
abstract: The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression.
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Jedynak
authors.affiliation: Department of Behavioral Neuroscience & Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kos
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland; Department of Biological Psychology, University of Finance and Management in Warsaw, 01-030 Warsaw, Poland; Behavior and Metabolism Research Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland. Electronic address: filipkowski@vizja.pl.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Filipkowski
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001973:Bromodeoxyuridine; D002908:Chronic Disease; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009483:Neuropsychological Tests; D013550:Swimming; D035501:Uncertainty
chemical_list: D000928:Antidepressive Agents; C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D005473:Fluoxetine; D001973:Bromodeoxyuridine
keywords: Adult neurogenesis; Dentate gyrus; Depression-like behavior; Fluoxetine; Stress