UC Riverside

Any type of locomotion requires central activation of motor systems, which can be suppressed by neurochemicals in a phenomena known as Central Fatigue (CF). Resistance to CF may evolve to support extreme locomotor abilities and may also occur in response to exercise training (phenotypic plasticity). I used the High-Runner (HR) mouse model to study CF in four replicate lines that have evolved in response to many generations of selective breeding for voluntary wheel running.

Serotonin is the most studied neurotransmitter in relation to CF. In my work, a serotonin inhibitory autoreceptor antagonist decreased endurance during forced treadmill exercise in HR mice, but not in mice from four non-selected Control (C) lines. Wheel running decreased in HR but not C mice at the highest dose of a serotonin agonist, but was unaffected by the antagonist. Therefore, serotonin signaling affects performance of both forced and voluntary exercise in a genotype-dependent manner.

I also tested effects of sports drinks and caffeine. Red Bull increased distance run voluntarily on wheels in both HR and C lines, but not did caffeine alone in water. Neither Red Bull nor caffeine significantly affected maximal aerobic capacity (VO2max), but both reduced post-trial tiredness. Gatorade did not affect wheel running or endurance in either line type. These results suggest that caffeine increases voluntary exercise levels of mice via effects on motivation or fatigue resistance, but not VO2max.

Finally, I analyzed strides of both sexes of HR and C mice on a motorized treadmill at speeds relevant to wheel running. Stance width was narrower in HR than C, and paw contact area and duty factor were greater in mini-muscle individuals (subset of HR mice with 50% reduced hindlimb muscle mass) than in normal-muscled HR or C. Many stride characteristics were affected by six days of wheel access. Thus, stride characteristics are responsive to selective breeding for locomotor behavior and exhibit phenotypic plasticity.

In conclusion, HR mice have evolved neurobiologically to resist serotonin-mediated CF, and morphologically and/or behaviorally to have a narrower stance. These results parallel wild animals that have evolved for, and humans that train for, extreme locomotor performance.