Decreased hippocampal neurogenesis following olfactory bulbectomy is reversed by repeated citalopram administration.
1. Whereas much progress has been made in the treatment of depression, the exact pathogenetic mechanisms of the disorder are still poorly understood. It has been proposed that one possible mechanism could be a decrease in adult hippocampal neurogenesis. 2. The olfactory bulbectomy (OB) in rats is widely accepted as an animal model of depression. In the present study, we investigated whether hippocampal neurogenesis is affected by an OB, and whether chronic citalopram, a serotonin selective reuptake inhibitor, counteracts OB-induced impairment of neurogenesis. 3. Our study shows that OB decreases proliferation of the neuronal precursors in the dentate gyrus and retards their differentiation into mature granule neurons. In OB rats, repeated administration of citalopram restores reduced proliferative activity and enhances the differentiation of precursors into mature calbindin-positive neurons. 4. The obtained data demonstrate that a citalopram-induced increase in neurogenesis in OB rats could be one possible mechanism by which antidepressants alleviate OB-induced depressive-like behavior.
Jaako-Movits
Külli
K
Department of Pharmacology, University of Tartu, 19 Ravila Street, 51014, Tartu, Estonia.
Zharkovsky
Tamara
T
Pedersen
Martin
M
Zharkovsky
Alexander
A
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009830:Olfactory Bulb / Q000502:physiology*; D010919:Placebos; D051381:Rats; D017208:Rats, Wistar
D000928:Antidepressive Agents; D010919:Placebos; D015283:Citalopram