Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

Abstract

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

Developmental fluoxetine and prenatal stress effects on serotonin, dopamine, and synaptophysin density in the PFC and hippocampus of offspring at weaning

“…Also, previous work we have done has found limited effects of sex on hippocampal plasticity in periadolescent rat offspring and we, and others, report more remarkable effects of sex after puberty, in rodent offspring, when circulating gonadal hormones play a prominent role (Rayen et al, 2015;Rayen et al, 2014;Pawluski et al, 2014). We feel our data points to important effects of prenatal stress and developmental fluoxetine exposure on the brain of juvenile offspring at weaning.…”

Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress

“…It is possible that cycling serotonin signaling may result in a different pattern of neural activation and DFosB accumulation than steady state increases, as homeostatic scaling may more strongly dampen effects that are constant (Nelson and Turrigiano, 2008). It will be important to investigate the differences in FosB isoform accumulation in mouse brain regions using additional methods that may more closely mimic clinically observed fluoxetine levels, such as oral or osmotic minipump administration (Pawluski et al, 2014). …”

Glyphosate and glyphosate‐based herbicide exposure during the peripartum period affects maternal brain plasticity, maternal behaviour and microbiome

“…Pregnant females were randomly assigned to three groups (n = 7 per group): Control (vehicle: MilliQ sterilised water; Merck KGaA, Darmstadt, Germany), glyphosate (5 mg kg ‐1 d ‐1 glyphosate isopropylamine salt; Dr Ehrenstorfer GmbH, Augsburg, Germany) and Roundup® 3Plus (Roundup; 5 mg kg ‐1 d ‐1 glyphosate isopropylamine salt equivalent; Monsanto, Creve Coeur, MO, USA; 170 g L ‐1 glyphosate acid, 229 g L ‐1 glyphosate isopropylamine salt) at GD9. Treatment was administered orally via biscuits every morning between 08.30 am and 09.30 am from GD10 to the weaning of the pups at postpartum day (PD)21. Females were fed one‐ninth of a vanilla wafer cookie (Crousti fondante; Delacre, Grand‐Bigard, Belgium) injected with treatment or vehicle.…”