Brief ReportCo-Treatment with Diazepam Prevents the Effects of Fluoxetine on the Proliferation and Survival of Hippocampal Dentate Granule Cells
Section snippets
Methods and Materials
For a complete description of methods, please see Supplement 1. Adult 9–10-week-old male C57BL/6 mice were used. All protocols were approved by the County Administrative board of Southern Finland.
For the time-course of fluoxetine treatment, mice received 1, 3, or 7 daily IP injections of fluoxetine (10 mg/kg/day) and then saline daily until day 14. This dose has been shown to increases neurogenesis and produces behavioral effects in the forced swim test (8).
Negative and positive control
Results
We first established and validated a rapid method for the determination of the proliferation rate (Supplement 2). The BrdU incorporation was assayed by immobilizing DNA onto a nylon membrane by a dot-blot apparatus and incubating the membrane with anti-BrdU antibody. Results with the dot-blot method were in agreement with those obtained by counting for BrdU-positive cells in tissue sections (Figure 1, Figure 2).
Whereas continuous treatment of mice with fluoxetine for 14 days significantly
Discussion
It has been suggested that antidepressant drugs increase neuronal plasticity, which gradually leads to the reorganization of functional network connectivity and thereby brings about the clinical antidepressant effect (1, 3, 17, 18). We recently reported that chronic fluoxetine treatment can, indeed, increase neuronal plasticity and reorganization of neuronal networks in the adult visual cortex (19). Chronic antidepressant treatment increases hippocampal neurogenesis and the survival of the
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