Nortriptyline mediates behavioral effects without affecting hippocampal cytogenesis in a genetic rat depression model

Neuroscience Letters
Åsa PetersénA A Mathé

Abstract

A prevailing hypothesis is that neurogenesis is reduced in depression and that the common mechanism for antidepressant treatments is to increase it in adult hippocampus. Reduced neurogenesis has been shown in healthy rats exposed to stress, but it has not yet been demonstrated in depressed patients. Emerging studies now indicate that selective serotonin reuptake inhibitors can, exert behavioral effects without affecting neurogenesis in mice. Here we extend our previous findings demonstrating that the number of BrdU positive cells in hippocampus was significantly higher in a rat model of depression, the Flinders Sensitive Line (FSL) compared to the control strain the Flinders Resistant Line (FRL). We also show that chronic treatment with the tricyclic antidepressant nortriptyline exerts behavioral effects in the Porsolt forced swim test without affecting hippocampal cell proliferation in the FSL model. These results strengthen the arguments against hypothesis of neurogenesis being necessary in etiology of depression and as requisite for effects of antidepressants, and illustrate the importance of using a disease model and not healthy animals to assess effects of potential therapies for major depressive disorder.

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Citations

Jan 21, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jennifer L OnksenJulie A Blendy
Apr 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Katsunori KobayashiHidenori Suzuki
Aug 30, 2011·Neuropeptides·Elli MikrouliÅsa Petersén
Dec 21, 2010·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Chiara PiubelliLucia Carboni
Dec 7, 2010·Progress in Neuro-psychopharmacology & Biological Psychiatry·I D NeumannA A Mathé
Jun 29, 2010·Progress in Neuro-psychopharmacology & Biological Psychiatry·Lucia CarboniEnrico Domenici
Feb 14, 2012·Acta Psychiatrica Scandinavica·Jan-Otto Ottosson, Håkan Odeberg
Nov 30, 2013·Neuroscience Letters·Stal Saurav ShresthaPer Svenningsson
Feb 9, 2012·Progress in Neuro-psychopharmacology & Biological Psychiatry·Thieza G MeloRegina H Silva
Oct 5, 2010·Neuroscience and Biobehavioral Reviews·Karen Wager-Smith, Athina Markou
May 29, 2018·Psychiatry and Clinical Neurosciences·Juzoh UmemoriEero Castrén
Jan 16, 2013·Pharmacological Reviews·David H Overstreet, Gregers Wegener
Apr 3, 2019·Digestive Diseases and Sciences·Ali NoorafshanSaied Karbalay-Doust
Sep 1, 2021·European Journal of Pharmacology·Cristian Bis-HumbertM Julia García-Fuster

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