Figure 1.

(A, B)1 hour, 24 hours, or 10 days after chronic social defeat, acH3K14, and total levels of histone H1 as a control, were quantified for hippocampus and amygdala (arrows) using immunohistochemistry. acH3K14 (normalized to total H1) was increased in hippocampus 24 hours after the last defeat, returned to normal within 10 days, and dropped below normal at 20 days after stress. This latter effect was normalized by 20 days of fluoxetine administrations. In contrast, acH3K14 was rapidly induced in amygdala and remained elevated for up to 24 hours before returning to normal. (C) In dorsal hippocampus, HDAC inhibitors have selective antidepressant-like effects. During a test for social interaction on experimental day 15, previously defeated mice spent significantly less time engaged in social interaction compared to controls under vehicle infusion conditions. Infusion of MS-275 (100 μM) had no effects on social avoidance. When assessed for sucrose preference, defeated mice exhibited significantly reduced preference for sucrose compared to controls, and this effect was reversed by HDAC inhibitor infusions. (D) When infused into the amygdala, MS-275 selectively attenuates stress-induced social avoidance. No significant effects of stress, or drug infusion, were observed during the sucrose preference test. When assessed with the forced swim test, defeated mice had significantly greater immobility, an effect no longer significant after MS-275. Differences between non-stressed controls and repeatedly defeated mice at each time point are denoted by * to indicate significance at p < 0.05. Isolated comparisons between bars are indicated by ^#, p < 0.05.