Microglial Activation in the Ventral Hippocampus Induced by Acute Social Defeat is Associated with Amygdala Activity

ABSTRACT Objective: Crosstalk between the brain and immune system has been implicated in the dev elo pm e nt ofmental disorders. The hypothalamic pituitary adrenal axis serves as an important bridge forthis process. This study aims to investigate the relationship between the fluctuation of plasmaglucocorticoid (GC) and microglial activation in the ventral hippocampus during social defeat. Methods: Intruder—residen t paradigm was used to establish the rodent model of acute social  de  feat.The plasma GC of intruder mice was obtained serially after social aggression. Simultaneously,social behaviors in the novel context, microglial activation, and inflammation in the ventralhippocampus were tested. Results: Results showed that plasma GC is high during 0.5-8 hours after social aggress  io  n and thenrecovered. Behavior test showed that social fear and avoidance in the novel context isobserved at day 3 after stimulation, and then social interaction increased at day 7 afterstimulation. High expression of glucocorticoid receptor (GR), NLRP3, and IL-18 accompaniedmicroglial activation in the ventral hippocampus at day 3, and then diminished at day 7 after stimulation. Ventral hippocampal inflammation is correlated with the changes in  socialbe havior. Additionally, muscimol, a GABA agonist, was bilaterally microinjected to basolateralamygdala, which alleviated the social avoidance and ventral hippocampal inflammation.  Conclusion:Our results suggested that acu te social defeat that leads to ventral hippocampal microglialactivation and inflammatory cytokine release depend on the activity of basolateral amygdala,but not the fluctuation of the plasma GC.