Stress-induced hyperthermia, the serotonin system and anxiety

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_1A receptor ligands reduce the SIH response, whereas acute administration of other serotonergic drugs (including 5-HT_1B, 5-HT₂ and 5-HT₃ 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.