Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans,\nthese medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent\nmodels is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present\nstudy was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine\nadministration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment,\nadult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and\nthree fluoxetine treatment doses: 0, 5, or 10mg/kg/day. Results show that a fluoxetine dose of 5mg/kg/day, but not 10mg/kg/day,\nresults in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods.\nFurthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at\na 5mg dose compared to a 10mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine\ntreatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can\ndifferentially affect hippocampal plasticity in the adult female rat.
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