117. Imipramine attenuates neuroinflammation and reverses stress-induced social avoidance

Abstract

Psychosocial stress is associated with altered immunity and mood disorders. We previously showed that repeated social defeat (RSD) promotes long-lasting microglial activation associated with social avoidance behavior, which is maintained for at least 24 days after cessation of RSD. Here our aims were to determine if Imipramine (tricyclic antidepressant) would reverse RSD-induced social avoidance and ameliorate neuroinflammatory responses. CB57/BL6 mice were divided into treatment groups. One group from RSD and controls received daily injections of Imipramine for 24 days, after 6 cycles of RSD. Two other groups were treated with saline. RSD mice spent significantly less time in the interaction zone when an aggressor was introduced into the cage. Administration of Imipramine reversed social avoidance behavior, significantly increasing the interaction time, so that it was similar to that of nondefeated mice. Moreover, 24 days of Imipramine treatment in RSD mice significantly decreased stress-induced mRNA levels of IL-6 in microglia. Following ex-vivo LPS stimulation, microglia from mice exposed to RSD, produced higher levels of IL-6, TNF-α, and IL-1B, and this was reversed by Imipramine. In a second experiment, Imipramine was added to drinking water confirming reversal of social avoidant behavior and decrease in mRNA expression of IL-6 in microglia. These data demonstrate that antidepressants may exert their effects in part by down-regulating neuroinflammation. This research was supported by NIH/NIMH R01 MH097243-02 and R01 MH093473-03.