Implication of the Central Nucleus of the Amygdala in Cardiovascular Regulation and Limiting Maximum Exercise Performance During High-intensity Exercise in Rats.

To date, the mechanism of central fatigue during high-intensity exercise has remained unclear. Here we elucidate the central mechanisms of cardiovascular regulation during high-intensity exercise with a focus on the hypothesis that amygdala activation acts to limit maximum exercise performance. In the first of three experiments, we probed the involvement of the central nucleus of the amygdala (CeA) in such regulation. Wistar rats were subjected to a maximum exercise test and their total running time and cardiovascular responses were compared before and after bilateral CeA lesions. Next, probing the role of central pathways, we tested whether high-intensity exercise activated neurons in CeA and/or the hypothalamic paraventricular nucleus (PVN) that project to the nucleus tractus solitarius (NTS). Finally, to understand the potential autonomic mechanisms affecting maximum exercise performance, we measured the cardiovascular responses in anesthetized rats to electrical microstimulation of the CeA, PVN, or both. We have found that (1) CeA lesions resulted in an increase in the total exercise time and the time at which an abrupt increase in arterial pressure appeared, indicating an apparent suppression of fatigue. (2) We confirmed that high-intensity exercise activated both the PVN-NTS and CeA-NTS pathways. Moreover, we discovered that (3) while stimulation of the CeA or PVN alone both induced pressor responses, their simultaneous stimulation also increased muscle vascular resistance. These results are evidence that cardiovascular responses during high-intensity exercise are affected by CeA activation, which acts to limit maximum exercise performance, and may implicate autonomic control modulating the PVN-NTS pathway via the CeA.