title: The role of neuroinflammation in the release of aversive odor cues from footshock-stressed rats: Implications for the neural mechanism of alarm pheromone.
abstract: Stressed animals have been known to release aversive chemosignals toward which conspecifics show avoidance-like responses. The present studies assessed whether inflammatory cytokine responses provoked by footshock stress modulate odor signals released from male rats. Male rats were exposed to 30min of intermittent footshock (60 shocks, 1.0mA, 100ms each, variable ITI of 30s) or remained in their home cages as non-stressed controls. Real time RT-PCR analysis of brain tissues indicated that footshock increased the pro-inflammatory cytokine, IL-1β and hnCRH as well as c-fos mRNA expressions in the paraventricular nucleus, and the bed nucleus of the stria terminalis, and increased plasma corticosterone levels. Soiled bedding collected from rats exposed to 30-min, but not 5-min, of footshock elicited a differential response, as expressed by decreased sniffing and increased avoidance in male test subjects. Soiled bedding from rats given corticosterone injection (s.c. 1.25 or 3.75mg/ml) 3h before bedding collection evoked no avoidance response in odor-recipients. Furthermore, ICV infusion of the anti-inflammatory cytokine IL-10 (20 or 200ng) into the stimulus animals 30-min before a 30-min footshock session, had no effect on plasma corticosterone levels in the stimulus animals, but attenuated the release of aversive odor as indicated by dose-dependently diminished avoidance in odor-recipient rats. These results demonstrated that stressed rats release odorant cues that cause other rats to move away from the source of the signal. Such stress-induced chemosignals may be mediated by inflammatory cytokine responses in the brain.
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, Vestal Parkway East, Binghamton, NY 13902-6000, USA. harakawa@umaryland.edu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arakawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Arakawa
authors.forename: Peter
authors.initials: P
authors.lastname: Blandino
authors.forename: Terrence
authors.initials: T
authors.lastname: Deak
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism; D003463:Cues; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation / Q000009:adverse effects / Q000379:methods; D005528:Foot; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D015213:Neuroimmunomodulation / Q000235:genetics / Q000502:physiology*; D009812:Odorants; D010675:Pheromones / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000502:physiology; D013315:Stress, Psychological / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D016207:Cytokines; D010675:Pheromones