Gene Expression Data Following Chronic Vehicle or Fluoxetine Treatment in Thirty Mouse Inbred Lines

In order to understand how biochemical and genetic differences correlate with treatment response, we measured depressive-like behavior, gene expression and the levels of thirty-six neurobiochemical analytes across a panel of genetically-diverse mouse inbred lines after chronic treatment with vehicle or fluoxetine. Neurobiochemical markers were chosen based on their putative molecular function within pathways proposed to underlie depression, which include neuronal transmission, HPA-axis regulation, and neuroimmune processes. The goal of this study is to establish genetic and biochemical biomarkers that can predict treatment response and to propose a molecular pathway that is critical in mediating anti-depressant response. Thirty mouse inbred strains (129S1/SvImJ, A/J, AKR/J, BALB/cJ, BTBRT T(+) tf/J, BUB/BnJ, C3H/HeJ, C57BL/6J, C57BLKS/J, C57BR/cdJ, C58/J, CBA/J, CE/J, DBA/2J, FVB/NJ, I/LnJ, LG/J, LP/J, MA/MyJ, MRL/MpJ, NOD/LtJ, NOR/LtJ, NZB/BlNJ, NZW/LacJ, P/J, PL/J, RIIIS/J, SJL/J, SM/J, and SWR/J) aged 5-6 weeks old were obtained from The Jackson Laboratory (Bar Harbor, ME). Male mice were kept in polycarbonate cages on a 12-hour light/dark cycle (lights on at 0700h) with access to food and water ad libitum. Following one week of habituation, mice were randomized to either control or treatment group (n=12 male mice per strain per treatment group). Mean water intake for each strain was determined previously by measuring daily water consumption for three weeks (n=12 mice per strain). This information, along with average weight measurements for each strain, was used to determine the amount of fluoxetine required to provide a daily oral dose of 0 or 18 mg/kg per mouse. After chronic administration of 0 or 18 mg/kg of fluoxetine for 21 days, mice aged 9-10 weeks were tested in a tail-suspension and open field apparatus. Upon completion of the study, mice were sacrificed by cervical dislocation and decapitation between 0900h and 1300h. Trunk blood was quickly collected and allowed to clot on ice. Following centrifugation, serum samples were collected and stored at -20C for determination of fluoxetine and norfluoxetine levels using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Micro-dissections of individual regions were performed on serial coronal brain sections (approximately 10 µm) that were placed on a cold metal block. Cortex was taken from the same section for each animal and immediately snaps frozen on dry ice. Samples were stored at -80C until analysis.