title: Divergent effects of brain interleukin-1ß in mediating fever, lethargy, anorexia and conditioned fear memory.
abstract: The influence of brain interleukin-1 (IL-1ß) on memory processes includes both detrimental and beneficial effects. To further explore the dynamics of brain IL-1ß in mediating learning and memory during acute sickness, we injected species-homologous rat IL-1ß (100ng/5μl) or vehicle (0.1% bovine serum albumin, 5μl) directly into the cisterna magna (i.c.m.) of male Sprague-Dawley rats. We measured, in parallel, body temperature, food intake, body mass, cage activity, as well as learning and memory using contextual fear conditioning. To investigate the effects of IL-1ß on learning and memory processes we used: (1) a retrograde experiment that involved injecting rats i.c.m. with IL-1ß immediately after training in the novel context, and (2) an anterograde experiment that involved injecting rats i.c.m. with IL-1ß two hours before training in the novel context. In addition, hypothalamic and hippocampal concentrations of IL-1β were measured at several time points following injection. Administration of IL-1ß induced fever, lethargy and anorexia for∼two-to-three days and increased the concentration of IL-1ß in the hippocampus and hypothalamus for at least eight hours. Training in the context immediately before IL-1ß administration (retrograde experiment), did not impair contextual and auditory fear memory. However, when training in the context occurred concurrently with elevated hippocampal IL-1ß levels, two hours after IL-1ß administration (anterograde experiment), contextual, but not auditory, fear memory was impaired. Our results show that there are instances where memory consolidation can occur concurrently with elevated levels of IL-1ß in the hippocampus, fever, anorexia and lethargy during acute short-term sickness.
authors.affiliation: Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, South Africa.
authors.forename: Tamzyn L
authors.initials: TL
authors.lastname: Baartman
authors.affiliation: Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, South Africa.
authors.forename: Tanya
authors.initials: T
authors.lastname: Swanepoel
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Barrientos
authors.affiliation: Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, South Africa.
authors.forename: Helen P
authors.initials: HP
authors.lastname: Laburn
authors.affiliation: Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, South Africa.
authors.forename: Duncan
authors.initials: D
authors.lastname: Mitchell
authors.affiliation: Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, South Africa. Electronic address: lois.harden@wits.ac.za.
authors.forename: Lois M
authors.initials: LM
authors.lastname: Harden
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005334:Fever / Q000139:chemically induced*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D053609:Lethargy / Q000139:chemically induced*; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects; D017207:Rats, Sprague-Dawley
chemical_list: D053583:Interleukin-1beta
keywords: Hippocampus; Hypothalamus; Memory consolidation; Pro-inflammatory cytokines; Sickness behaviours