The role of brain interleukin-1 in stress-enhanced fear learning.

Posttraumatic stress disorder (PTSD) has been shown to be associated with pro-inflammatory markers， including elevated plasma levels of interleukin-1β (IL-1β). However， the precise role of neuroinflammation and central immune signaling on the development of this debilitating psychological disorder is not known. Here， we used stress-enhanced fear learning (SEFL)， an animal model of the disorder， to examine the role of central IL-1β in PTSD. The results show that the severe stressor in SEFL induces a time-dependent increase in IL-1β immunoreactivity and mRNA expression within the dentate gyrus of the dorsal hippocampus (DH). There was no increase in IL-1β in the basolateral amygdala or the perirhinal cortex. Moreover， blocking the action of IL-1β following the severe stressor with IL-1 receptor antagonist (10 μg， intracerebroventricular (i.c.v.)， 24 and 48 h after the stressor) prevented the development of SEFL. To provide further support for the role of IL-1β in the development of SEFL， we show that systemic morphine， a treatment which is known to reduce both PTSD and SEFL， also reduces IL-1β expression in the DH induced by the severe stressor. These studies provide the first evidence that IL-1 is involved SEFL and suggest that IL-1 signaling in the brain may have a critical role in the development of PTSD.