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. 2015 Dec 30;2(4):457-75.
doi: 10.1080/23328940.2015.1119615. eCollection 2015 Oct-Dec.

Thermoregulatory responses in exercising rats: methodological aspects and relevance to human physiology

Samuel Penna Wanner  1 , Thales Nicolau Prímola-Gomes  2 , Washington Pires  1 , Juliana Bohnen Guimarães  3 , Alexandre Sérvulo Ribeiro Hudson  1 , Ana Cançado Kunstetter  1 , Cletiana Gonçalves Fonseca  1 , Lucas Rios Drummond  2 , William Coutinho Damasceno  1 , Francisco Teixeira-Coelho  4
Affiliations

Thermoregulatory responses in exercising rats: methodological aspects and relevance to human physiology

Samuel Penna Wanner et al. Temperature (Austin). .

Abstract

Rats are used worldwide in experiments that aim to investigate the physiological responses induced by a physical exercise session. Changes in body temperature regulation, which may affect both the performance and the health of exercising rats, are evident among these physiological responses. Despite the universal use of rats in biomedical research involving exercise, investigators often overlook important methodological issues that hamper the accurate measurement of clear thermoregulatory responses. Moreover, much debate exists regarding whether the outcome of rat experiments can be extrapolated to human physiology, including thermal physiology. Herein, we described the impact of different exercise intensities, durations and protocols and environmental conditions on running-induced thermoregulatory changes. We focused on treadmill running because this type of exercise allows for precise control of the exercise intensity and the measurement of autonomic thermoeffectors associated with heat production and loss. Some methodological issues regarding rat experiments, such as the sites for body temperature measurements and the time of day at which experiments are performed, were also discussed. In addition, we analyzed the influence of a high body surface area-to-mass ratio and limited evaporative cooling on the exercise-induced thermoregulatory responses of running rats and then compared these responses in rats to those observed in humans. Collectively, the data presented in this review represent a reference source for investigators interested in studying exercise thermoregulation in rats. In addition, the present data indicate that the thermoregulatory responses of exercising rats can be extrapolated, with some important limitations, to human thermal physiology.

Keywords: body temperature, brain temperature; environment; exercise; heat; hyperthermia; physical exertion; rat; thermoregulation; treadmill running.

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Figures

Figure 1.
Figure 1.
Abdominal and tail-skin temperatures of rats subjected to a 45-min period of treadmill running at a constant speed of 18 m/min and an ambient temperature of ∼24°C. These experiments were conducted under conditions of compensable heat stress (moderate-intensity exercise in a temperate environment). The data used to plot this graph were taken from experiments reported in the following manuscript: Wanner SP, Leite LH, Guimarães JB, Coimbra CC. Increased brain L-arginine availability facilitates cutaneous heat loss induced by running exercise. Clin Exp Pharmacol Physiol 2015; 42:609-16. Copyright © 2015 John Wiley and Sons. Used with permission.
Figure 2.
Figure 2.
Thalamic and abdominal temperatures (A) and the thalamic-abdominal temperature differential of rats (B) subjected to constant-speed treadmill running until fatigue. * denotes a significant difference (p< 0.05) compared with the abdominal temperature. Panel C shows the brain-abdominal temperature differential of running rats at volitional fatigue. The brain temperature was measured at different sites (i.e., the brain cortex, thalamus and hypothalamus). All of these experiments were conducted in temperate environments (ambient temperatures ranging from 24 to 25°C). Please note that these temperature differentials were obtained from experiments with distinct exercise intensities and protocols. The data measured were taken from the experiments reported in the following manuscripts: (i) thalamus - Damasceno WC, Pires W, Lima MR, Lima NR, Wanner SP. The dynamics of physical exercise-induced increases in thalamic and abdominal temperatures are modified by central cholinergic stimulation. Neurosci Lett 2015; 590:193-8. © 2015 John Wiley and Sons. Reproduced by permission of John Wiley and Sons. Permission to reuse must be obtained from the rightsholder; (ii) hypothalamus - Fonseca CG, Pires W, Lima MR, Guimarães JB, Lima NR, Wanner SP. Hypothalamic temperature of rats subjected to treadmill running in a cold environment. PLoS One 2014; 9:e111501. Open-access manuscript; (iii) brain cortex - Drummond LR et al., unpublished data. The rats were subjected to an incremental-speed exercise at an ambient temperature of 25°C. The brain cortex temperature was measured using a thermistor inserted at the following stereotaxic coordinates: anteroposterior: 3 mm anterior to the bregma; mediolateral: 3 mm right to the midline; and dorsoventral: 1.8 mm dorsal to the skull. The abdominal temperature was measured by telemetry. This experiment was approved by the Ethics Commission for Animal Use of the Universidade Federal de Viçosa (Brazil; protocol number 58/2012).
Figure 3.
Figure 3.
Cortical brain temperature of rats that were subjected to treadmill running until fatigue at 3 different speeds (18, 21, and 24 m/min). The ambient temperature was controlled at 25.2 ± 0.2°C by the use of air conditioning. * denotes a significant difference (p< 0.05) compared with the 21 m/min and 18 m/min trials. + denotes a significant difference (p < 0.05) compared with the 18 m/min trial. The data used to plot this graph were taken from the control experiments reported in the following manuscript: Kunstetter AC, Wanner SP, Madeira LG, Wilke CF, Rodrigues LO, Lima NR. Association between the increase in brain temperature and physical performance at different exercise intensities and protocols in a temperate environment. Braz J Med Biol Res 2014; 47:679-88. Open-access manuscript.
Figure 4.
Figure 4.
Abdominal temperature of rats subjected to treadmill running until fatigue at a constant speed of 20 m/min at 3 ambient temperatures (i.e., 8, 12 and 15°C). * denotes a significant difference (p< 0.05) compared with the 12°C trial. + denotes a significant difference (p < 0.05) compared with the 15°C trial. The graph was modified from: Guimarães JB, Wanner SP, Machado SC, Lima MR, Cordeiro LM, Pires W, La Guardia RB, Silami-Garcia E, Rodrigues LO, Lima NR. Fatigue is mediated by cholinoceptors within the ventromedial hypothalamus independent of changes in core temperature. Scand J Med Sci Sports 2013; 23:46-56. Copyright © 2013 John Wiley and Sons. Used with permission.
Figure 5.
Figure 5.
Correlation between the ambient temperature and the change in the abdominal temperature of rats subjected to fatiguing treadmill running. The treadmill speed was set to 20-21 m/min, and the inclination was set to 0-5%. The criterion to determine fatigue was the same in these 3 studies, i.e., the inability to keep the pace with the treadmill, as indicated by exposure to electrical stimulation for 10 consecutive seconds. The data used to plot this graph were taken from experiments reported in the following manuscripts: (i) Rodrigues LO, Oliveira A, Lima NR, Machado-Moreira CA. Heat storage rate and acute fatigue in rats. Braz J Med Biol Res 2003; 36:131-5. Open-access manuscript. (ii) Guimarães JB, Wanner SP, Machado SC, Lima MR, Cordeiro LM, Pires W, La Guardia RB, Silami-Garcia E, Rodrigues LO, Lima NR. Fatigue is mediated by cholinoceptors within the ventromedial hypothalamus independent of changes in core temperature. Scand J Med Sci Sports 2013; 23:46-56. Copyright © 2013 John Wiley and Sons. Used with permission; (iii) Fonseca CG, Pires W, Lima MR, Guimarães JB, Lima NR, Wanner SP. Hypothalamic temperature of rats subjected to treadmill running in a cold environment. PLoS One 2014; 9:e111501. Open-access manuscript.
Figure 6.
Figure 6.
Change in brain temperature induced by manual handling and the insertion of the thermistor for recording the brain cortex temperature (A). The rats were kept in their home cages, and the ambient temperature was controlled at 25.2 ± 0.2°C by the use of air conditioning. The data used to plot this graph were taken from the control experiments reported in the following manuscript: Kunstetter AC, Wanner SP, Madeira LG, Wilke CF, Rodrigues LO, Lima NR. Association between the increase in brain temperature and physical performance at different exercise intensities and protocols in a temperate environment. Braz J Med Biol Res 2014; 47:679-88. Open-access manuscript.
Figure 7.
Figure 7.
Change in the abdominal temperature of a representative rat that was placed on a treadmill (blue) and 2 h later was subjected to constant-speed treadmill running at 18 m/min (red). A thermocouple remained attached to the rat's tail, and a microinjection needle was placed inside a brain guide cannula throughout the experiment. The ambient temperature was controlled at 24.1 ± 0.4°C by the use of air conditioning. The data used to plot this graph were taken from the experiments reported in the following manuscript: Wanner SP, Leite LH, Guimarães JB, Coimbra CC. Increased brain L-arginine availability facilitates cutaneous heat loss induced by running exercise. Clin Exp Pharmacol Physiol 2015; 42:609-16. © John Wiley and Sons. Reproduced by permission of John Wiley and Sons. Permission to reuse must be obtained from the rightsholder.
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