RESEARCH ARTICLE


Stress-Induced Hyperthermia, the Serotonin System and Anxiety



Christiaan H. Vinkers*, 1, Berend Olivier1, 2, J. Adriaan Bouwknecht3, Lucianne Groenink1, Jocelien D.A. Olivier4, 5
1 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS) and Rudolf Magnus Institute of Neuroscience, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands
2 Department of Psychiatry, Yale University School of Medicine, New Haven, USA
3 Department of Neuroscience, Pharmaceutical Research & Development, Johnson and Johnson, Beerse, Belgium
4 Department of Molecular Animal Physiology, Radboud University Nijmegen, Nijmegen, The Netherlands
5 Donders Institute for Brain, Cognition and Behavior: Department for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Article Information


Identifiers and Pagination:

Year: 2010
Volume: 4
First Page: 15
Last Page: 29
Publisher Id: TOPHARMJ-3-15
DOI: 10.2174/1874143601004010015

Article History:

Received Date: 20/10/2009
Revision Received Date: 19/4/2010
Acceptance Date: 20/4/2010
Electronic publication date: 2/6/2010
Collection year: 2010

H. Vinkers et al.; Licensee Bentham Open

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the the Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neurosciences, Utrecht University, Sorbonnelaan 16, 3584CA Utrecht, The Netherlands; Tel: +31(0)302531599; Fax: +31(0)302537900; E-mail: c.h.vinkers@uu.nl


Abstract

The serotonin (5-HT) system plays a key role in the pathophysiology of psychiatric disorders including mood and anxiety disorders. A role for serotonin in stress-related disorders is further supported by the fact that clinically effective treatments for these disorders alter serotonergic neurotransmission. The therapeutic potential of serotonergic pharmacological interventions has resulted in a variety of preclinical approaches to study the serotonin system. Of these, the stress-induced hyperthermia (SIH) paradigm has been extensively used to study the serotonin system at a preclinical level. The SIH response uses the transient rise in body temperature in response to a stressor which can be reduced using anxiolytic drugs including benzodiazepines, CRF receptor antagonists and serotonergic ligands.

The present review aims to discuss the acute and chronic effects of 5-HT ligands on the SIH response. Also, the SIH response in genetically modified mice that lack or overexpress specific serotonergic receptor subtypes or the serotonin transporter will be summarized. 5-HT receptor ligands reduce the SIH response, whereas acute administration of other serotonergic drugs (including 5-HT, 5-HT and 5-HT modulators and SSRIs) generally does not influence the SIH response. Also, the SIH paradigm is generally insensitive to detect the anxiolytic effects of chronic serotonergic antidepressants in rodents, and serotonergic drugs that have been found to reduce the SIH response acutely do so irrespective of the healthy or pathological status of an individual.

Keywords: Stress, serotonin, 5-HT, SERT, autonomic nervous system, model.