Divergent effects of brain interleukin-1ß in mediating fever, lethargy, anorexia and conditioned fear memory

Behav Brain Res. 2017 May 1:324:155-163. doi: 10.1016/j.bbr.2017.02.020. Epub 2017 Feb 14.

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.

Keywords: Hippocampus; Hypothalamus; Memory consolidation; Pro-inflammatory cytokines; Sickness behaviours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anorexia / chemically induced*
  • Body Temperature / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology
  • Eating / drug effects
  • Fear / drug effects
  • Fear / physiology*
  • Fever / chemically induced*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Interleukin-1beta / administration & dosage
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / physiology*
  • Lethargy / chemically induced*
  • Male
  • Memory Consolidation / drug effects
  • Memory Consolidation / physiology*
  • Motor Activity / drug effects
  • Rats, Sprague-Dawley

Substances

  • Interleukin-1beta