Meeting Abstract

108.6  Sunday, Jan. 6  Manipulating central fatigue in mice bred for high voluntary wheel running using a serotonin agonist and antagonist CLAGHORN, GC*; FONSECA, IAT; FIELDER, J; BARBER, C; GARLAND JR, T; Univ. of California, Riverside; Univ. of California, Riverside; Univ. of California, Riverside; Univ. of California, Riverside; Univ. of California, Riverside gclag001@ucr.edu

Central fatigue limits the performance of an organism to less than the level that might be predicted by classic models of physiological maxima, and numerous studies have shown that the concentration of serotonin (5-hydroxytryptamine; 5-HT) in the brain increases at the onset of fatigue. Central fatigue has been studied primarily in relation to forced exercise, and not voluntary exercise. We hypothesized that neurobiological differences related to central fatigue could explain evolutionary differences in both endurance capacity and levels of voluntary exercise. Mice from 4 lines that had been selectively bred for high voluntary wheel running (HR lines) for over 60 generations were previously shown to have higher endurance than those from 4 non-selected control (C) lines. We predicted that a 5-HT1A agonist (8-OH-DPAT) or antagonist (WAY 100 635) would alter endurance and the evolutionary advantage of HR lines during forced exercise. Male mice were endurance-tested three times using a forced treadmill protocol at 7-9 weeks of age under a randomized series of three pharmaceutical conditions, a vehicle injection, a low-dose of the designated drug (0.2 mg/kg body mass for 8-OH-DPAT and 35 µg/kg WAY 100 635) or a high dose (2 mg/kg body mass for 8-OH-DPAT and 350 µg/kg WAY 100 635). Time and distance to exhaustion were recorded. The same mice were then given wheel access for 14 days, until wheel running had reached an apparent plateau, and then subjected to a similar set of injections during the nightly peak of wheel running (1 injection/night) while wheel revolutions were recorded automatically. Supported by NSF Predoctoral Fellowship to GC and NSF grant IOS-1121273 to TG.