Intra-amygdala microinfusion of IL-6 impairs the auditory fear conditioning of rats via JAK/STAT activation

Behav Brain Res. 2014 Dec 15:275:88-95. doi: 10.1016/j.bbr.2014.08.052. Epub 2014 Sep 3.

Abstract

Though accumulating literature implicates that cytokines are involved in the pathophysiology of mental disorders, the role of interleukin-6 (IL-6) in learning and memory functions remains unresolved. The present study was undertaken to investigate the effect of IL-6 on amygdala-dependent fear learning. Adult Wistar rats were used along with the auditory fear conditioning test and pharmacological techniques. The data showed that infusions of IL-6, aimed at the amygdala, dose-dependently impaired the acquisition and extinction of conditioned fear. In addition, the results in the Western blot analysis confirmed that JAK/STAT was temporally activated-phosphorylated by the IL-6 treatment. Moreover, the rats were treated with JSI-124, a JAK/STAT3 inhibitor, prior to the IL-6 treatment showed a significant decrease in the IL-6 induced impairments of fear conditioning. Taken together, our results demonstrate that the learning behavior of rats in the auditory fear conditioning could be modulated by IL-6 via the amygdala. Furthermore, the JAK/STAT3 activation in the amygdala seemed to play a role in the IL-6 mediated behavioral alterations of rats in auditory fear learning.

Keywords: Auditory; Behavioral; Cognitive dysfunction; Cytokine; Fear memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / adverse effects
  • Amygdala / drug effects*
  • Amygdala / physiology
  • Analysis of Variance
  • Animals
  • Conditioning, Classical / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Enzyme Inhibitors / administration & dosage
  • Extinction, Psychological / drug effects
  • Fear / drug effects*
  • Freezing Reaction, Cataleptic / drug effects
  • Interleukin-6 / pharmacology*
  • Learning Disabilities / chemically induced*
  • Learning Disabilities / prevention & control
  • Microinjections
  • Phosphorylation / drug effects
  • Rats
  • STAT Transcription Factors / metabolism*
  • Time Factors
  • Triterpenes / administration & dosage

Substances

  • Enzyme Inhibitors
  • Interleukin-6
  • STAT Transcription Factors
  • Triterpenes
  • cucurbitacin I