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

• Published in: Neuropsychopharmacology (New York, N.Y.) N.Y.), 2015-03, Vol.40 (5), p.1289-1296
• Main Authors: Jones, Meghan E, Lebonville, Christina L, Barrus, Daniel, Lysle, Donald T
• Format: Article
• Language: English
• Subjects: Animals; Anxiety; Behavior; Brain - drug effects; Brain - metabolism; Cytokines; Disease Models, Animal; Electroshock; Experiments; Fear - drug effects; Fear - physiology; Immunohistochemistry; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - metabolism; Laboratories; Learning - physiology; Male; Memory; Morphine; Morphine - pharmacology; Narcotics - pharmacology; Neurosciences; Original; Post traumatic stress disorder; Psychopathology; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Stress Disorders, Post-Traumatic - drug therapy; Stress Disorders, Post-Traumatic - metabolism; Stress, Psychological - drug therapy; Stress, Psychological - metabolism; Time Factors; Tumor necrosis factor-TNF
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/npp.2014.317

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.