Rodrigues, Alex G., Nilo R. V. Lima, Cândido C. Coimbra, and Umeko Marubayashi. Intracerebroventricular physostigmine facilitates heat loss mechanisms in running rats. J Appl Physiol 97: 333-338, 2004. First published March 19, 2004 10.1152/japplphysiol. 00742.2003.-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 l of 5 ϫ 10 Ϫ3 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 Phytreated animals showed a lower core heating rate (0.022 Ϯ 0.003°C/ min Phy vs. 0.033 Ϯ 0.003°C/min Sal; P Ͻ 0.02), lower heat storage (285 Ϯ 37 cal Phy vs. 436 Ϯ 34 cal Sal; P Ͻ 0.02) and lower core temperature at fatigue point than the Sal-treated group (38.5 Ϯ 0.1°C Phy vs. 39.0 Ϯ 0.1°C Sal; P Ͻ 0.05). However, despite the lower core heating rate, heat storage, and core temperature at fatigue, the Phytreated rats showed a similar running time compared with the Saltreated 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. body temperature; oxygen consumption; central cholinergic system; fatigue ACCORDING TO THE HEAT REGULATION hypothesis (52), high body temperature is the result rather than the cause of control, whereas metabolic heat production is an independent variable that is constantly adjusted to meet the changing need for energy and heat loss adjusted to match heat production. Heat loss has known physiological effectors that may be influenced and limited by other nonthermoregulatory restraints such as cardiovascular and respiratory control. Therefore, delay in its adjustment during exercise may limit heat loss, increase both heat storage and body core temperature, and induce fatigue.Internal body temperature is considered to be a limiting factor during prolonged physical exercise (14,16,39). However, the mechanisms responsible for exercise fatigue related to increasing body temperature are still not well understood, including whether exercise temperature increase is due to a rise in set point levels or occurs passively through an unwanted accumulation of heat (2). Controversy also exists as to whether there is a critical absolute value of BT, heat storage rate, or both that determines the point of fatigue. Fuller et al. (...