Chapter 2.1 Stress-induced hyperthermia

Abstract

Abstract When animals are confronted with a stressor, they respond by an extensive stress response, amongst which a rise in body temperature is prominent. This stress-induced hyperthermia (SIH) is a rapid response reaching a maximum within 10–15 min after the start of the stress-inducing stimulus. In mice, the amplitude and duration of SIH seem to depend on the intensity of the stressor: a short-lasting stress like measuring the rectal body temperature or injection of a drug leads to an SIH of maximally 1–1.5°C and lasts about 45 min, whereas a novel cage stress enhances body temperature 2–2.5°C and has a longer duration. However, large strain differences exist and intrinsic differences in basal core body temperature over the day are present between strains (C57BL/6J, 129SvEv, Swiss–Webster). There is a dispute in the literature whether SIH is a (emotional) fever or a hyperthermia. The absence of effects of an antipyretic dose of acetylacylic acid (aspirin) on both a rectal procedure and a novel cage stress supports the hypothesis that SIH is a real hyperthermia. The standard SIH paradigm in singly housed mice is sensitive to anxiolytic-like effects of various psychoactive drugs (GABA A -benzodiazepine receptor agonists, alcohol, and 5-HT 1A receptor agonists). An advantage of the method is that it simultaneously measures intrinsic effects of drugs on the core body temperature and that these effects are independent from the effects on SIH. The SIH procedure seems unable to find anxiogenic-like effects of drugs, presumably due to a ceiling effect in the enhanced temperature. The SIH procedure is very suitable to measure the effect of a genetic manipulation and also to study effects of drugs in mutants, as illustrated in 5-HT 1A and 5-HT 1B receptor knockout and CRF-overexpressing mice. In rats, a similar procedure as in mice ( T = −60 min injection; T = 0 min first rectal temperature measurement and T = + 15 min, second rectal measurement) was developed that generated a reliable stress-induced hyperthermia, that is again sensitive to anxiolytic-like effects of various anxiolytics (benzodiazepines, alcohol, 5-HT 1A receptor agonists). Stress-induced hyperthermia is a simple, reproducible and species-, and strain-independent phenomenon associated with encountering stressful stimuli. The SIH procedure in mice is optimally suited to measure the putative modulating effects of drugs, but also of mutations on a physiological parameter reflecting anxiety. Moreover, intrinsic effects on body temperature are also measured, thereby creating an animal paradigm of anxiety that is, in contrast to almost all other anxiety tests, independent of locomotion. The latter is one of the biggest confounds in animal models of anxiety because of interference due to, e.g., sedation or psychostimulation.