Chronic fluoxetine administration to juvenile rats prevents age-associated dendritic spine proliferation in hippocampus.

The density of dendritic spines, the postsynaptic sites of most excitatory synapses, increases during the first 2 postnatal months in rat hippocampus. Significant alterations in hippocampal levels of serotonin and norepinephrine impact synaptic development during this time period. In the present study, dendritic spine density was studied in the hippocampus (CA1) and dentate gyrus of juvenile rats acutely and chronically exposed to antidepressant drugs that act on serotonin and norepinephrine. One group of 21-day-old rats was given a single injection of a serotonin specific re-uptake inhibitor (fluoxetine or fluvoxamine), a norepinephrine-specific re-uptake inhibitor (desipramine), or saline and killed after 24 h. A second group of rats was injected daily, beginning on postnatal day (PN) 21, for 3 weeks. This group was further subdivided into rats that were killed 1 day or 21 days after the last injection. Golgi analysis showed that a single injection of fluvoxamine produced a significant increase in dendritic spine density in stratum radiatum of CA1 and in the dentate gyrus. Further, acute treatment with all three antidepressants increased the total length of secondary dendrites in CA1, with fluoxetine and desipramine increasing the number of secondary dendrites as well. In fluoxetine-treated animals killed on days 42 or 62 (1 or 21 days post-treatment, respectively), dendritic spine density remained at levels present in CA1 at 21 days. These results show that acute antidepressant treatment can impact dendritic length and spine density, and raise the possibility that chronic fluoxetine treatment arrests spine development into young adulthood.