The effect of monoamines reuptake inhibitors on aerobic exercise performance in bank voles from a selection experiment.

Exercise performance depends on both physiological abilities (e.g., muscle strength) and behavioral characteristics (e.g., motivation). We tested the hypothesis that evolution of increased aerobic exercise performance can be facilitated by evolution of neuropsychological mechanisms responsible for motivation to undertake physical activity. We used a unique model system: lines of bank voles Myodes glareolus selected for high swim-induced aerobic metabolism ("aerobic" A lines). In generation 21, voles from the 4 A lines achieved a 57% higher "voluntary maximum" swim-induced aerobic metabolism (VO2swim) than voles from 4 unselected, "control" C lines. In C lines, VO2swim was 9% lower than the maximum forced-exercise aerobic metabolism (VO2run; P = 0.007), while in A lines it was even higher than VO2run, although not significantly (4%, P = 0.15). Thus, we hypothesized that selection changed both the aerobic capacity and the neuronal mechanisms behind motivation to undertake activity. We investigated the influence of reuptake inhibitors of dopamine (DARI), serotonin (SSRI), and norepinephrine (NERI) on VO2swim. The drugs decreased VO2swim both in C and A lines (% decrease compared with saline: DARI 8%, P < 0.001; SSRI 6%, P < 0.001; NERI 8%, P < 0.001), but the proportional response differed between selection directions only for NERI (stronger effect in C lines: P = 0.008) and the difference was marginally non-significant for SSRI (P = 0.07) and DARI (P = 0.06). Thus, the results suggest that all the 3 monoamines are involved in signaling pathways controlling the motivation to be active and that norepinephrine could have played a role in the evolution of increased aerobic exercise performance in our animal model.

Is Experimental Evolution of an Increased Aerobic Exercise Performance in Bank Voles Mediated by Endocannabinoid Signaling Pathway?

The level of physical activity achieved in a given situation depends on both physiological abilities and behavioral characteristics (motivation). We used a unique animal model to test a hypothesis that evolution of an increased aerobic exercise performance can be facilitated by evolution of motivation to undertake physical activity, mediated by brain endocannabinoid system. Bank voles (Myodes glareolus) from "aerobic" A lines selected for 22 generations for high swim-induced aerobic metabolism (VO2swim) achieved 65% higher "voluntary maximum" VO2swim than voles from unselected, "control" C lines. In C lines, VO2swim was 24% lower than the maximum forced-running aerobic metabolism (VO2run), while in A lines VO2swim and VO2run were practically the same. Thus, the selection changed both the aerobic capacity and motivation to exercise at the top performance level. We applied a pharmacological treatment manipulation to test a hypothesis that the endocannabinoid signaling pathway 1) affects the voles performance in the aerobic exercise trials, and 2) has been modified in the selection process. Administration of the CB1 receptor antagonist (Rimonabant) did not affect the level of metabolism, but administration of the endocannabinoid reuptake inhibitor (AM404) decreased VO2swim both in A and C lines (4%, p = 0.03) and tended to decrease VO2run (2%, p = 0.07). The significant effect of AM404 suggests the involvement of endocannabinoids in signaling pathways controlling the motivation to be active. However, the response to AM404 did not differ between A and C lines (interaction effect, p ≥ 0.29). Thus, the results did not provide a support to the hypothesis that modifications of endocannabinoid signaling have played a role in the evolution of increased aerobic exercise performance in our experimental evolution model system. SUMMARY STATEMENT: The results corroborated involvement of endocannabinoids in the regulation of physical activity, but did not support the hypothesis that modification of endocannabinoid signaling played a role in the evolution of increased aerobic exercise performance in our experimental evolution model.

Hindlimb muscle fibre size and glycogen stores in bank voles with increased aerobic exercise metabolism.

To test hypotheses concerning physiological factors limiting the rate of aerobic exercise metabolism, we used a unique experimental evolution model: lines of bank voles selected for high swim-induced aerobic metabolism (A) and unselected, control lines (C). We investigated putative adaptations that result in the increased performance of the hindlimb muscle (gastrocnemius joined with plantaris). The body mass-adjusted muscle mass was higher in A-lines (0.093 g) than in C-lines (0.083 g; P=0.01). However, selection did not affect mean muscle fibre cross-sectional area (P=0.34) or glycogen content assessed with a histochemical periodic acid-Schiff reaction (PAS; P=0.82). The results suggest that the increased aerobic performance is achieved by an increase of total muscle mass, without major qualitative changes in the muscle fibre architecture. However, such a conclusion should be treated with caution, because other modifications, such as increased density of capillaries or mitochondria, could occur.

A dopamine and noradrenaline reuptake inhibitor (bupropion) does not alter exercise performance of bank voles.

Physical performance is determined both by biophysical and physiological limitations and behavioral characteristic, specifically motivation. We applied an experimental evolution approach combined with pharmacological manipulation to test the hypothesis that evolution of increased aerobic exercise performance can be triggered by evolution of motivation to undertake physical activity. We used a unique model system: bank voles from A lines, selected for high swim-induced aerobic metabolism (VO2swim), which achieved a 61% higher mass-adjusted VO2swim than those from unselected C lines. Because the voles could float on the water surface with only a minimum activity, the maximum rate of metabolism achieved in that test depended not only on their aerobic capacity, but also on motivation to undertake intensive activity. Therefore, we hypothesized that signaling of neurotransmitters putatively involved in regulating physical activity (dopamine and noradrenaline) had changed in response to selection. We measured VO2swim after intraperitoneal injections of saline or the norepinephrine and dopamine reuptake inhibitor bupropion (20 mg/kg or 30 mg/kg). Additionally, we measured forced-exercise VO2 (VO2max). In C lines, VO2swim (mass-adjusted mean ± standard error (SE): 4.0 ± 0.1 mLO2/min) was lower than VO2max (5.0 ± 0.1 mLO2/min), but in A lines VO2swim (6.0 ± 0.1 mLO2/min) was as high as VO2max (6.0 ± 0.1 mLO2/min). Thus, the selection effectively changed both the physiological-physical performance limit and mechanisms responsible for the willingness to undertake vigorous locomotor activity. Surprisingly, the drug had no effect on the achieved level of VO2swim. Thus, the results did not allow firm conclusions concerning involvement of these neurotransmitters in evolution of increased aerobic exercise performance in the experimental evolution model system.