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Neurosci Biobehav Rev. 2007;31(1):41-59. Epub 2006 Apr 17.

The stress-induced hyperthermia paradigm as a physiological animal model for anxiety: a review of pharmacological and genetic studies in the mouse.

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Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.


This paper reviews the function, brain mechanisms and pharmacology of stress-induced hyperthermia (SIH) in a broad context. Hyperthermia itself is induced by all stressful stimuli and can be found across numerous species, including humans. As a model for anxiety, the process of insertion of a rectal probe increases temperature ranging from about 0.5-1.5 degrees C in 10-15min is called SIH. This temperature increase can be blocked by anxiolytic drugs. The methodological as well as pharmacological aspects of the group- (G-SIH) and singly housed (SIH) version of the paradigm are described in detail. Also, an overview is presented about studies using the SIH procedure in genetically modified mice together with the potential interference with immunological induction of a febrile response. The paper also presents data that highlight some of the limitations of the SIH procedure for use of drugs like nicotine, which contain particular characteristics such as short in vivo half-life, and/or disturbance of thermoregulation. The advantages and disadvantages of the SIH procedure as a physiological model of anxiety are discussed.

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