title: Escitalopram reduces increased hippocampal cytogenesis in a genetic rat depression model.
abstract: Hippocampal neurogenesis is potentially implicated in etiology of depression and as the final common mechanism underlying antidepressant treatments. However, decreased neurogenesis has not been demonstrated in depressed patients and, in animals, reduced cytogenesis was shown in healthy rats exposed to stressors, but, so far, not in models of depression. Here we report that the number of BrdU positive cells in hippocampus was (1) significantly higher in a rat model of depression, the Flinders Sensitive Line (FSL) compared to control FRL, (2) increased in both FSL and FRL following maternal separation, (3) reduced by escitalopram treatment in maternally separated animals to the level found in non-separated animals. These results argue against the prevailing hypothesis that adult cytogenesis is reduced in depression and that the common mechanism underlying antidepressant treatments is to increase adult cytogenesis. The results also point to the importance of using a disease model and not healthy animals for testing effects of potential treatments for human depression and suggest other cellular mechanisms of action than those that had previously been proposed for escitalopram.
authors.affiliation: Translational Neuroendocrine Research Unit, BMC D11, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden.
authors.forename: Asa
authors.initials: A
authors.lastname: Petersén
authors.forename: Gitta
authors.initials: G
authors.lastname: Wörtwein
authors.forename: Susanne H M
authors.initials: SH
authors.lastname: Gruber
authors.forename: Aleksander A
authors.initials: AA
authors.lastname: Mathé
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D015283:Citalopram / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology*; D008426:Maternal Deprivation; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013550:Swimming
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D001973:Bromodeoxyuridine