Muscle pH decreases during exercise, which may impair function. Endurance training typically reduces muscle buffering capacity as a result of changes in fiber-type composition, but existing comparisons of species that vary in activity level are ambiguous. We hypothesized that high-runner (HR) lines of mice from an experiment that breeds mice for voluntary wheel running would have altered muscle buffering capacity as compared with their non-selected control counterparts. We also expected that 6 days of wheel access, as used in the selection protocol, would reduce buffering capacity, especially for HR mice. Finally, we expected a subset of HR mice with the 'mini-muscle' phenotype to have relatively low buffering capacity as a result of fewer type IIb fibers. We tested non-bicarbonate buffering capacity of thigh muscles. Only HR mice expressing the mini-muscle phenotype had significantly reduced buffering capacity, females had lower buffering capacity than males, and wheel access had no significant effect.

A ketogenic diet (KD) has been proposed as a treatment for many conditions including obesity, diabetes, epilepsy, and Parkinson's Disease. Various studies have shown its effects on health and lifespan in model organisms suggesting that it is beneficial for many individuals. Some concern exists that KD might negatively impact anabolic signaling through the mTOR pathway, but the molecular signaling effects of the diet remain largely unexplored, particularly in skeletal muscle. The purpose of this study, therefore, was to determine how KD affects downstream mTOR signaling in skeletal muscle from young and old rats. Young adult (YA; 5 mo.) and old (O; 28 mo.) male Fisher 344 rats were isocalorically fed either a ketogenic diet (KD; Envigo Teklad Custom Diet, TD.10911; 22.4% protein, 77.1% fat, 0.5% carbohydrates) or standard diet (STD; Envigo Teklad Rodent Diet, 8604; 32% protein, 14% fat, 54% carbohydrate) for four weeks. Soleus muscles were harvested and assessed for muscle size and effects on p70 ribosomal protein S6 kinase (S6k) phosphorylation. Soleus muscles from YA KD rats were ~11% smaller than for corresponding YA STD rats, and O KD soleus muscles were ~6% larger vs. O STD muscles, though neither of these differences were significant. Phosphorylation of S6k was significantly (p < 0.05) decreased 75% in YA KD vs. YA STD. S6k phosphorylation was reduced 88% in O muscles, but, in contrast to the YA muscles, was increased by ~400% by KD vs. STD in O muscles. Based on this evidence, we conclude that in slow‐twitch soleus muscles, administration of KD can decrease skeletal muscle mTOR signaling in YA muscles and increase its signaling in O muscles.Support or Funding InformationThis work was supported by a Brigham Young University Gerontology Program award.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Behavioral addictions can come in many forms, including overeating, gambling and overexercising. All addictions share a common mechanism involving activation of the natural reward circuit and reinforcement learning, but the extent to which motivation for natural and drug rewards share similar neurogenetic mechanisms remains unknown. A unique mouse genetic model in which four replicate lines of female mice were selectively bred (>76 generations) for high voluntary wheel running (High Runner or HR lines) alongside four non‐selected control (C) lines were used to test the hypothesis that high motivation for exercise is associated with greater reward for cocaine (20 mg/kg) and methylphenidate (10 mg/kg) using the conditioned place preference (CPP) test. HR mice run ~three times as many revolutions/day as C mice, but the extent to which they have increased motivation for other rewards is unknown. Both HR and C mice displayed significant CPP for cocaine and methylphenidate, but with no statistical difference between linetypes for either drug. Taken together, results suggest that selective breeding for increased voluntary running has modified the reward circuit in the brain in a way that increases motivation for running without affecting cocaine or methylphenidate reward.

Running acts as a natural reward and shares features with other rewarding behaviors, such as eating or taking drugs of abuse. Exercise is even proposed to have addictive properties, as humans and rodents have shown signs of “withdrawal,” including anxiety and depression, after being denied exercise. Conditioned place preference (CPP) is a neuro‐behavioral test of reward and reinforcement, widely used in studies of addictive processes in rodents. In typical protocols, individuals receive a reward (e.g., cocaine injection) paired with a specific environment (usually a specific floor texture) several times and are then tested for preference of the conditioned environment as compared with a different environment in which they had not received a reward (e.g., saline injection). We studied CPP in a unique exercise model of 4 replicate lines of mice selectively bred for high voluntary wheel running (High Runner or HR lines) and 4 non‐selected control (C) lines. HR mice run ~3‐times as much as C mice on a daily basis, partly because of evolutionary changes in their reward and motivational systems. We hypothesized that HR mice would differ from C in the extent to which they show a CPP following conditioning with rewarding drugs and/or wheel running. In experiment 1, HR and C mice were tested for CPP with cocaine as the reward. Both HR and C mice were significantly conditioned by cocaine, with no statistical difference between groups in the degree of conditioning. In experiment 2, mice were tested for CPP with wheel access as the reward. Specifically, mice were granted or not granted wheel access for 10 days, and each day removed from wheels or standard cages during peak wheel running and placed in CPP chambers for 30 minutes. Preliminary results show no significant conditioning by either HR or C mice. In a recent experiment 3, mice were tested for CPP with Ritalin as the reward, following the same protocol as experiment 1. Functioning as a dopamine transporter blocker, the drug Ritalin has been shown to decrease wheel running of HR mice while increasing running by C mice. Thus, we hypothesize a significant difference in the degree of conditioning between HR and C mice with Ritalin.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.