Gene Expression Profile Of Depression Mouse Model After Chronic Treatment With Fluoxetine

Depression is a mood disorder which is characterized by constant feelings of sadness, decreased interest or pleasure and even thoughts of suicide. Accumulating evidence showed that chronic stress is involved in the pathophysiology of depression. Fluoxetine, one of the third generation selective serotonin reuptake inhibitor antidepressants, is used medically in the treatment of depression. Although it is well known that Fluoxetine works by increasing the amount of serotonin in the synaptic gap that helps maintain mental balance, the "monoamine hypothesis" has failed to explain the observation that weeks of treatment with Fluoxetine are required before clinical efficacy becomes apparent. The exactly mechanisms underlying the effect of Fluoxetine in depression treatment leaves unclear after decades of research.[Objective] The intent of this study was to determine (1) the efficacy of our paradigm of chronic mild stress model to simulate the status of depression and (2) mRNA expression profile alterations in CMS model mice after chronic (8 weeks) treatment of Fluoxetine.[Method] Animal model was built with male BALB/c mice by exposing the animals to a paradigm of chronic unpredictable stresses including 9 different stressors for a consecutive course of 10 weeks. On the fifteenth day of stress, sucrose preference test was performed and animals were grouped in accordance to their sucrose consumption per gram body weight. Drug administration was also started from the fifteenth day. Fluoxetine (0.25mg/kg) was administrated through oral pathway, while the solvent of Fluoxetine was administrated to the animals in control group. Stress stimuli were maintained and drug administrations were carried out for the following 8 weeks. After animal model establishment, namely, from the tenth week of the experiment, animals' depression-like behaviors were assessed by a panel of behavioral assays, including one-hour single bottle sucrose preference test, locomotor movement, forced swim test and Morris water maze test was performed to evaluate the capacity of Fluoxetine to change spatial learning and memory ability under CMS model. After behavioral tests, the animals were sacrificed their brain tissues were prepared for the later cDNA microarray assay. The high-throughput cDNA microarray technique was introduced in the present study to explore the mechanisms of action of Fluoxetine, based on a chronic mild stress model that tried to simulate the real conditions which may induce depression in humans. Tissues from cortex and hippocampus were used for the microarray experiments.