A Brief Opportunity to Run Does Not Function as a Reinforcer for Mice Selected for High Daily Wheel‐running Rates

Belke, Terry W.; Garland, Theodore

doi:10.1901/jeab.2007.62-06

Cited by 67 publications

(60 citation statements)

References 28 publications

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“…Previous studies demonstrate that the reward circuitry, including dopaminergic and endocannabinoid pathways, have been altered in HR mice. 8,10,11 Therefore, it is possible that the motivation for wheel running and sensitivity of the 'activitystat' responds differently to a WD in HR as compared with C mice.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 Various changes in locomotor performance, behavior and neurobiology (especially related to motivation for wheel running) have been observed in the HR lines. [10][11][12] For instance, treadmill endurance capacity is elevated in HR mice, 13 as is maximal oxygen consumption. 14 Despite the continued selection since generation 16, HR mice seem to be at a selection limit, the biological causes of which are not yet clear.…”

Section: Introductionmentioning

confidence: 99%

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Western diet increases wheel running in mice selectively bred for high voluntary wheel running

2010

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Objective: Mice from a long-term selective breeding experiment for high voluntary wheel running offer a unique model to examine the contributions of genetic and environmental factors in determining the aspects of behavior and metabolism relevant to body-weight regulation and obesity. Starting with generation 16 and continuing through to generation 52, mice from the four replicate high runner (HR) lines have run 2.5-3-fold more revolutions per day as compared with four non-selected control (C) lines, but the nature of this apparent selection limit is not understood. We hypothesized that it might involve the availability of dietary lipids. Methods: Wheel running, food consumption (Teklad Rodent Diet (W) 8604, 14% kJ from fat; or Harlan Teklad TD.88137 Western Diet (WD), 42% kJ from fat) and body mass were measured over 1-2-week intervals in 100 males for 2 months starting 3 days after weaning. Results: WD was obesogenic for both HR and C, significantly increasing both body mass and retroperitoneal fat pad mass, the latter even when controlling statistically for wheel-running distance and caloric intake. The HR mice had significantly less fat than C mice, explainable statistically by their greater running distance. On adjusting for body mass, HR mice showed higher caloric intake than C mice, also explainable by their higher running. Accounting for body mass and running, WD initially caused increased caloric intake in both HR and C, but this effect was reversed during the last four weeks of the study. Western diet had little or no effect on wheel running in C mice, but increased revolutions per day by as much as 75% in HR mice, mainly through increased time spent running. Conclusion: The remarkable stimulation of wheel running by WD in HR mice may involve fuel usage during prolonged endurance exercise and/or direct behavioral effects on motivation. Their unique behavioral responses to WD may render HR mice an important model for understanding the control of voluntary activity levels.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Western diet increases wheel running in mice selectively bred for high voluntary wheel running

2010

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“…As discussed elsewhere, several lines of evidence indicate that the motivation for wheel running and/or the reward received from running has been altered in the HR lines Rhodes et al, 2005;Belke and Garland, 2007). The capacity for sustained, aerobically supported exercise has also increased in the HR lines, as demonstrated by increased endurance (Meek et al, 2009) and increases maximum oxygen consumption [V O2,max (Swallow et al, 1998b;Rezende et al, 2005;Rezende et al, 2006a)] during forced treadmill exercise.…”

Section: Introductionmentioning

confidence: 97%

Erythropoietin elevates but not voluntary wheel running in mice

Kolb

Kelly

Middleton

et al. 2010

Journal of Experimental Biology

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SUMMARYVoluntary activity is a complex trait, comprising both behavioral (motivation, reward) and anatomical/physiological (ability) elements. In the present study, oxygen transport was investigated as a possible limitation to further increases in running by four replicate lines of mice that have been selectively bred for high voluntary wheel running and have reached an apparent selection limit. To increase oxygen transport capacity, erythrocyte density was elevated by the administration of an erythropoietin (EPO) analogue. Mice were given two EPO injections, two days apart, at one of two dose levels (100 or 300gkg -1 and 300gkg -1 dose levels (overall mean of 4.5gdl -1 increase). EPO treatment significantly increased V O2,max by ~5% in both the HR and C lines, with no dose ϫ line type interaction. However, wheel running (revolutions per day) did not increase with EPO treatment in either the HR or C lines, and in fact significantly decreased at the higher dose in both line types. These results suggest that neither [Hb] per se nor V O2,max is limiting voluntary wheel running in the HR lines. Moreover, we hypothesize that the decrease in wheel running at the higher dose of EPO may reflect direct action on the reward pathway of the brain.Key words: artificial selection, central limitation, experimental evolution, maximum metabolic rate, oxygen transport, peripheral limitation, respiratory exchange ratio, selection limit, symmorphosis. THE JOURNAL OF EXPERIMENTAL BIOLOGY 511Erythropoietin elevates V O 2 ,max in mice aerobically supported exercise has also increased in the HR lines, as demonstrated by increased endurance (Meek et al., 2009) and increases maximum oxygen consumption [V O2,max (Swallow et al., 1998b;Rezende et al., 2005;Rezende et al., 2006a)] during forced treadmill exercise. However, the trait, or group of traits, that is limiting to even higher levels of wheel running in the HR lines remains an open question. Results to date indicate that glycogen depletion during nightly running is not responsible for the limitation (Gomes et al., 2009) nor are the HR mice limited by their ability to process enough energy to support the increased energy demands of running (Koteja et al., 1999;Koteja et al., 2001;Vaanholt et al., 2007a;Rezende et al., 2009).One of the main predictors of endurance-running ability is wholeorganism aerobic capacity (Wagner, 1996;Bassett and Howley, 2000;Lucia et al., 2001;Calbet et al., 2006;Noakes, 2007;Levine, 2008;Noakes, 2009). All else being equal, the higher the maximum aerobic capacity, the higher the maximum sustainable running speed. Maximum oxygen consumption defines the upper limits of the cardiovascular/respiratory system and of aerobic ability in general (for a review, see Levine, 2008). The ultimate determinant of organismal aerobic capacity occurs at the 'sink' of tissue oxygen consumption but all of the sequential steps of oxygen transport, from ventilatory convection in the lungs to oxygen diffusion in the peripheral tissues, contribute to V O2,max (Taylor an...

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“…For example, Sherwin and Nicol (1996) demonstrated that mice are motivated to engage in wheel running, even when the cost of gaining access to a wheel is increased by requiring shallow water traverses. Not only are mice apparently willing to incur a cost to gain access to a running wheel, but also operant conditioning studies have demonstrated that both rats and mice are motivated to lever press for the opportunity to run (Belke 2006;Belke and Garland 2007 (Cagniard et al 2006;Davis et al 2008;Garland et al 2011b). The interactions of these redundant neural systems are currently poorly understood (Lenard and Berthoud 2008), but it has been demonstrated in mice (Kumar et al 2010) and humans (Cai et al 2006) that food intake and physical activity, both components of energy balance, may be governed by a similar underlying genetic architecture.…”

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confidence: 99%

“…For example, Sherwin and Nicol (1996) demonstrated that mice are motivated to engage in wheel running, even when the cost of gaining access to a wheel is increased by requiring shallow water traverses. Not only are mice apparently willing to incur a cost to gain access to a running wheel, but also operant conditioning studies have demonstrated that both rats and mice are motivated to lever press for the opportunity to run (Belke 2006;Belke and Garland 2007). In addition, selective breeding for both elevated endurance capacity in rats and elevated wheel running in mice has resulted in alterations to neurobiological pathways that appear to delay the onset of exercise-induced fatigue (rats: Foley et al 2006) and increase motivation for wheel-running behavior (mice: Rhodes et al 2005).…”

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confidence: 99%

Functional Genomic Architecture of Predisposition to Voluntary Exercise in Mice: Expression QTL in the Brain

Kelly¹,

Nehrenberg²,

Hua³

et al. 2012

Genetics

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The biological basis of voluntary exercise is complex and simultaneously controlled by peripheral (ability) and central (motivation) mechanisms. The accompanying natural reward, potential addiction, and the motivation associated with exercise are hypothesized to be regulated by multiple brain regions, neurotransmitters, peptides, and hormones. We generated a large (n = 815) advanced intercross line of mice (G4) derived from a line selectively bred for increased wheel running (high runner) and the C57BL/6J inbred strain. We previously mapped multiple quantitative trait loci (QTL) that contribute to the biological control of voluntary exercise levels, body weight, and composition, as well as changes in body weight and composition in response to short-term exercise. Currently, using a subset of the G4 population (n = 244), we examined the transcriptional landscape relevant to neurobiological aspects of voluntary exercise by means of global mRNA expression profiles from brain tissue. We identified genome-wide expression quantitative trait loci (eQTL) regulating variation in mRNA abundance and determined the mode of gene action and the cis- and/or trans-acting nature of each eQTL. Subsets of cis-acting eQTL, colocalizing with QTL for exercise or body composition traits, were used to identify candidate genes based on both positional and functional evidence, which were further filtered by correlational and exclusion mapping analyses. Specifically, we discuss six plausible candidate genes (Insig2, Socs2, DBY, Arrdc4, Prcp, IL15) and their potential role in the regulation of voluntary activity, body composition, and their interactions. These results develop a potential initial model of the underlying functional genomic architecture of predisposition to voluntary exercise and its effects on body weight and composition within a neurophysiological framework.

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A Brief Opportunity to Run Does Not Function as a Reinforcer for Mice Selected for High Daily Wheel‐running Rates

Cited by 67 publications

References 28 publications

Western diet increases wheel running in mice selectively bred for high voluntary wheel running

Western diet increases wheel running in mice selectively bred for high voluntary wheel running

Erythropoietin elevates but not voluntary wheel running in mice

Functional Genomic Architecture of Predisposition to Voluntary Exercise in Mice: Expression QTL in the Brain

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