Central fatigue induced by losartan involves brain serotonin and dopamine content.

PURPOSE: To investigate the influence of angiotensin II (Ang II) AT1 receptors blockade on central fatigue induced by brain content of serotonin (5-HT) and dopamine (DA) during exercise. METHODS: Losartan (Los) was intracerebroventricularly injected in rats before running until fatigue (n = 6 per group). At fatigue, brains were quickly removed for measurement of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), DA, and 3,4-dihydroxyphenylacetic acid by high-pressure liquid chromatography in the preoptic area, hypothalamus, hippocampus, and frontal cortex. RESULTS: Intracerebroventricular injection of Los increased 5-HT content in the preoptic area and hypothalamus. Such results correlated positively with body heating rate and inversely with time to fatigue. On the other hand, time to fatigue was directly correlated with the diminished concentration of 5-HT in the hippocampus of Los rats. Although the levels of DA were not affected by Los treatment during exercise in any of the brain areas studied, a higher 5-HT/DA ratio was seen in the hypothalamus of Los animals. This higher hypothalamic 5-HT/DA ratio correlated positively with body heating rate and negatively with time to fatigue. CONCLUSIONS: Our results show that central fatigue due to hyperthermia and increased body heating rate induced by central Ang II AT1 receptor blockade in exercising rats is related with higher 5-HT content in the preoptic area and hypothalamus as well as with decreased levels of this neurotransmitter in the hippocampus. Furthermore, the interaction between 5-HT and DA within the hypothalamus seems to contribute to hyperthermia and premature central fatigue after angiotensinergic inhibition.

Performance-enhancing and thermoregulatory effects of intracerebroventricular dopamine in running rats.

To assess the role of central dopamine on metabolic rate, heat balance and running performance, 2.0 microL of 5 x 10(-3)M dopamine solution (DA) or 0.15M NaCl (SAL) was intracerebroventricularly injected in Wistar rats 1 min before running on a motor-driven treadmill, according to a graded exercise protocol, until fatigue. Oxygen consumption (VO(2)) and body temperature (T(b)) were recorded at rest, during exercise, and after 30 min of recovery. DA induced a marked increase in workload (approximately 45%, p<0.05). At fatigue point, DA-injected rats attained approximately 29% higher maximum oxygen consumption (VO(2max)) and approximately 0.75 degrees C higher T(b) than SAL-injected rats. Despite the higher VO(2max) and T(b) attained during exercise, DA-treated rats reached VO(2) basal values within the same recovery period and dissipated heat approximately 33% faster than SAL-treated rats (p<0.05). The mechanical efficiency loss rate was approximately 40% lower in DA than in SAL-treated rats (p<0.05), however, the heat storage was approximately 35% higher in the DA group (p<0.05). Our results demonstrate that increased DA availability in the brain has a performance-enhancing effect, which is mediated by improvements in the tolerance to heat storage and increases in the metabolic rate induced by graded exercise. These data provide further evidence that central activation of dopaminergic pathways plays an important role in exercise performance.

Heat loss during exercise is related to serotonin activity in the preoptic area.

To investigate the influence of the central cholinergic system on thermoregulation and brain serotonin concentration during exercise; 2 microl of physostigmine (5x10 M) or saline solution was injected into the lateral cerebral ventricle of running rats. At fatigue, brains were quickly removed and serotonin and 5-hydroxyindoleacetic acid were measured in the preoptic area, hypothalamus, frontal cortex, and hippocampus. Physostigmine injection attenuated hyperthermia and exercise-induced heat storage that was closely related to the serotonin content in the preoptic area. Physostigmine treatment also increased the heat dissipation by decreasing core temperature threshold for vasodilation. In conclusion, our data indicated that stimulation of the central cholinergic system promotes heat dissipation in running rats that is related to decreased serotonin content in the preoptic area.

Intracerebroventricular physostigmine facilitates heat loss mechanisms in running rats.

The aim of this study was to evaluate the participation of central cholinergic transmission in the regulation of metabolic rate, core temperature, and heat storage in untrained rats submitted to exercise on a treadmill (20 m/min, 5% inclination) until fatigue. The animals were separated into eight experimental groups, and core temperature or metabolic rate was measured in the rats while they were exercising or while they were at rest after injection of 2 microl of 5 x 10(-3) M physostigmine (Phy) or 0.15 M NaCl solution (Sal) into the lateral cerebral ventricle. Metabolic rate was determined by the indirect calorimetry system, and colonic temperature was recorded as an index of core temperature. In resting animals, Phy induced only a small increase in metabolic rate compared with Sal injection, without having any effect on core temperature. During exercise, the Phy-treated animals showed a lower core heating rate (0.022 +/- 0.003 degrees C/min Phy vs. 0.033 +/- 0.003 degrees C/min Sal; P < 0.02), lower heat storage (285 +/- 37 cal Phy vs. 436 +/- 34 cal Sal; P < 0.02) and lower core temperature at fatigue point than the Sal-treated group (38.5 +/- 0.1 degrees C Phy vs. 39.0 +/- 0.1 degrees C Sal; P < 0.05). However, despite the lower core heating rate, heat storage, and core temperature at fatigue, the Phy-treated rats showed a similar running time compared with the Sal-treated group. We conclude that the activation of the central cholinergic system during exercise increases heat dissipation and attenuates the exercise-induced increase in core temperature without affecting running performance.