Increase in neurogenesis and behavioural benefit after chronic fluoxetine treatment in Wistar rats.
OBJECTIVE
Disturbances in hippocampal neurogenesis may be involved in the pathophysiology of depression and it has been argued that an increase in the generation of new nerve cells in the hippocampus is involved in the mechanism of action of antidepressants.


METHODS
Adult Wistar rats were treated with fluoxetine (10 mg/kg) 1 h, daily for 5 (subchronic) or 28 days (chronic) before the Novelty Suppressed Feeding test was performed. Cell proliferation and neurogenesis were analysed using the markers 5-bromo-deoxy-2'-uridine, Ki-67, and doublecortin.


RESULTS
A significant behavioural effect was found after 28 days of fluoxetine administration. However, no behavioural improvement was demonstrated after acute and subchronic treatment with fluoxetine. We further demonstrate that chronic antidepressant treatment increases cell proliferation as well as neurogenesis in the dentate gyrus, here using Wistar rats.


CONCLUSIONS
In further development of antidepressants, neurogenesis may serve as an important parameter to examine the efficacy and mechanism of action of novel drugs.
Marcussen
A B
AB
Department of Pharmacology Target Research, H. Lundbeck A/S, Valby, Denmark.
Flagstad
P
P
Kristjansen
P E G
PE
Johansen
F F
FF
Englund
U
U
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D018891:Dentate Gyrus / Q000166:cytology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004334:Drug Administration Schedule; D005247:Feeding Behavior / Q000187:drug effects; D005473:Fluoxetine / Q000008:administration & dosage*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*
D001973:Bromodeoxyuridine; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005473:Fluoxetine; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D017367:Selective Serotonin Reuptake Inhibitors; C000714848:Dcx protein, rat