Muscarinic receptors within the ventromedial hypothalamic nuclei modulate metabolic rate during physical exercise

▶ Bilateral injections of methylatropine into the VMH markedly reduce performance. ▶ Muscarinic receptors in the VMH are activated during exercise to modulate VO2. ▶ Blocking muscarinic transmission leads to a faster increase in VO2 during exercise. ▶ Blocking muscarinic transmission reduces mechanical efficiency during exercise. ▶ Decreased mechanical efficiency is related to an early interruption of exercise. The involvement of muscarinic cholinoceptors within the ventromedial hypothalamic nuclei (VMH) on the exercise-induced increase in oxygen consumption (VO2) was investigated. Rats were fitted with bilateral cannulae into the VMH for local delivery of drugs. On the day of the experiments, the animals were submitted to running exercise (20m/min; 5% grade) until the point of fatigue. VO2 was continuously measured after bilateral injections of either 0.2μL of 5×10−9mol methylatropine or 0.15M NaCl solution into the VMH. Control experiments were conducted in freely moving rats on the treadmill. Muscarinic blockade within the VMH reduced time to fatigue by 32% and enhanced the increase in VO2 from the 8th until the 17th min of exercise when compared to the control trial. In fact, time to fatigue was negatively correlated to the rate of increase in VO2 (r2=0.747; P