Imipramine attenuates neuroinflammatory signaling and reverses stress-induced social avoidance
artículo original
Fecha
2015-05Autor
Ramírez Chan, Karol Gabriela
Shea, Daniel T.
McKim, Daniel B.
Reader, Brenda F.
Sheridan, John F.
Metadatos
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Psychosocial stress is associated with altered immunity, anxiety and depression. Previously we showed
that repeated social defeat (RSD) promoted microglia activation and social avoidance behavior that persisted
for 24 days after cessation of RSD. The aim of the present study was to determine if imipramine (a
tricyclic antidepressant) would reverse RSD-induced social avoidance and ameliorate neuroinflammatory
responses. To test this, C57BL/6 mice were divided into treatment groups. One group from RSD and controls
received daily injections of imipramine for 24 days, following 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 present in the cage. Administration of imipramine reversed social avoidance behavior, significantly
increasing the interaction time, so that it was similar to that of control mice. Moreover, 24 days of imipramine
treatment in RSD mice significantly decreased stress-induced mRNA levels for IL-6 in brain
microglia. Following ex vivo LPS stimulation, microglia from mice exposed to RSD, had higher mRNA
expression of IL-6, TNF-a, and IL-1b, and this was reversed by imipramine treatment. In a second experiment,
imipramine was added to drinking water confirming the reversal of social avoidant behavior and
decrease in mRNA expression of IL-6 in microglia. These data suggest that the antidepressant imipramine
may exert its effect, in part, by down-regulating microglial activation.