Differential activation of CRF receptor subtypes removes stress-induced memory deficit and anxiety

Cedomir Todorovic, Jelena Radulovic, Olaf Jahn, Marko Radulovic, Tessi Sherrin, Cathrin Hippel, Joachim Spiess

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


The objective of this study was to investigate the role of corticotropin-releasing factor receptors 1 (CRF1) and 2 (CRF 2) in anxiety-like behavior and learning of C57BL/6J mice after exposure to a stressful stimulus. When C57BL/6J mice were exposed to immobilization (1 h) serving as stressful stimulus, context- and tone-dependent fear conditioning were impaired if the training followed immediately after immobilization. The stress-induced impairment of context-dependent fear conditioning was prevented by specific blockade of CRF2 of the lateral septum (LS) with anti-sauvagine-30. Immobilization did not only affect conditioned fear, but also enhanced, through CRF2 of the LS, anxiety-like behavior determined with the elevated plus maze. Recovery from stress-induced anxiety and impairment of context-dependent fear conditioning was observed after 1 h delay of training and required hippocampal CRF1, as indicated by the finding that this recovery was prevented by blockade of intrahippocampal CRF1. It was concluded that exposure to a stressor initially affected both anxiety-like behavior and contextual conditioned fear through septal CRF2, while the later activation of hippocampal CRF1 resulted in the return to baseline levels of both processes. Intraventricular injection of mouse urocortin 2, a CRF2-selective agonist, removed the stress-induced anxiety and learning impairment, but did not reduce the activation of the hypothalamic pituitary adrenal axis indicative of the hormonal stress response. We propose that the enhanced anxiety is the component of the stress response responsible for the memory deficit.

Original languageEnglish (US)
Pages (from-to)3385-3397
Number of pages13
JournalEuropean Journal of Neuroscience
Issue number11
StatePublished - Jun 2007
Externally publishedYes


  • Anxiety
  • C57BL/6J mice
  • Corticotropin-releasing factor receptors
  • Fear conditioning
  • Hippocampus
  • Lateral septum

ASJC Scopus subject areas

  • Neuroscience(all)


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