Translational aspects of pharmacological research into anxiety disorders: the stress-induced hyperthermia (SIH) paradigm

Christiaan H Vinkers, Meg J V van Bogaert, Marianne Klanker, S Mechiel Korte, Ronald Oosting, Taleen Hanania, Seth C Hopkins, Berend Olivier, Lucianne Groenink

Research output: Contribution to journalReview articleAcademicpeer-review

83 Citations (Scopus)


In anxiety research, the search for models with sufficient clinical predictive validity to support the translation of animal studies on anxiolytic drugs to clinical research is often challenging. This review describes the stress-induced hyperthermia (SIH) paradigm, a model that studies the activation of the autonomic nervous system in response to stress by measuring body temperature. The reproducible and robust SIH response, combined with ease of testing, make the SIH paradigm very suitable for drug screening. We will review the current knowledge on the neurobiology of the SIH response, discuss the role of GABA(A) and serotonin (5-HT) pharmacology, as well as how the SIH response relates to infectious fever. Furthermore, we will present novel data on the SIH response variance across different mice and their sensitivity to anxiolytic drugs. The SIH response is an autonomic stress response that can be successfully studied at the level of its physiology, pharmacology, neurobiology and genetics and possesses excellent animal-to-human translational properties.

Original languageEnglish
Pages (from-to)407-25
Number of pages19
JournalEuropean journal of pharmacology
Issue number2-3
Publication statusPublished - 13 May 2008
Externally publishedYes


  • Animals
  • Anxiety Disorders/drug therapy
  • Body Temperature Regulation/physiology
  • Disease Models, Animal
  • Female
  • Fever/etiology
  • Humans
  • Male
  • Receptors, GABA-A/drug effects
  • Serotonin/physiology
  • Species Specificity
  • Stress, Psychological/complications

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