title: The role of brain interleukin-1 in stress-enhanced fear learning.
abstract: 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.
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC USA.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Jones
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Lebonville
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Barrus
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC USA.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Lysle
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004597:Electroshock; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism*; D013997:Time Factors
chemical_list: C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D009294:Narcotics; D012333:RNA, Messenger; D009020:Morphine