This study examined the effects of chronic fluoxetine (Prozac) administration on mouse behavior and hippocampal neurophysiology. Mice received either 14mg/kg/day or 22mg/kg/day of fluoxetine in their drinking water for 4 weeks. Behavioral tests found that the higher dose was associated with erratic home cage behavior. Electrophysiology recordings revealed reduced firing rates of hippocampal granule cells in these mice. The dematuration of these cells correlated with increased anxiety-like behaviors, suggesting chronic fluoxetine can induce behavioral destabilization through effects on hippocampal plasticity.