Access To Wheel Research Articles

Locus coeruleus galanin expression is enhanced after exercise in rats selectively bred for high capacity for aerobic activity

The neuropeptide galanin extensively coexists with norepinephrine in locus coeruleus (LC) neurons. Previous research in this laboratory has demonstrated that unlimited access to activity wheels in the home cage increases mRNA for galanin (GAL) in the LC, and that GAL mediates some of the beneficial effects of exercise on brain function. To assess whether capacity for aerobic exercise modulates this upregulation in galanin mRNA, three heterogeneous rat models were tested: rats selectively bred for (1) high intrinsic (untrained) aerobic capacity (High Capacity Runners, HCR) and (2) low intrinsic aerobic capacity (Low Capacity Runners, LCR) and (3) unselected Sprague–Dawley (SD) rats with and without free access to running wheels for 3 weeks. Following this exercise protocol, mRNA for tyrosine hydroxylase (TH) and GAL was measured in the LC. The wheel running distances between the three models were significantly different, and age contributed as a significant covariate. Both selection and wheel access condition significantly affected GAL mRNA expression, but not TH mRNA expression. GAL was elevated in exercising HCR and SD rats compared to sedentary rats while LCR rats did not differ between conditions. Overall running distance significantly correlated with GAL mRNA expression, but not with TH mRNA expression. No strain differences in GAL or TH gene expression were observed in sedentary rats. Thus, intrinsic aerobic running capacity influences GAL gene expression in the LC only insofar as actual running behavior is concerned; aerobic capacity does not influence GAL expression in addition to changes associated with running.

Phenotypic and evolutionary plasticity of body composition in rats selectively bred for high endurance capacity

We investigated the effects of genetic selection and prolonged wheel access (8 wk) on food consumption and body composition in lines of rats selected for high and low intrinsic (untrained) endurance running capacity (HCR and LCR, respectively) to test the generality of phenotypic correlations between physical activity levels, aerobic capacity, and body composition. HCR rats ran more minutes per day on activity wheels than LCR rats, supporting the hypothesis that voluntary activity and physiological capacity are genetically correlated (self-induced adaptive plasticity). Both treatments (selection and wheel access) significantly affected food consumption. HCR rats consumed and digested more food than LCR rats. Access to running wheels did not result in changes in overall body mass, but lean body mass increased and percent body fat decreased in both lines. Selection for high endurance capacity resulted in hypertrophy of the heart and kidneys and decreased long intestine length. We found significant phenotypic flexibility in a number of organ masses after wheel running. Specifically, access to running wheels resulted in hypertrophy of the heart, liver, kidney, stomach, and small and large intestines in LCR and HCR rats. The selected line×wheel access interaction was significantly greater in HCR rats in relative mass for the heart and lung. Compared with LCR rats, HCR rats fortify wheel running with increased food consumption along with greater hypertrophy of key organs for O2 transport.

Adult hippocampal neurogenesis and c-Fos induction during escalation of voluntary wheel running in C57BL/6J mice

Voluntary wheel running activates dentate gyrus granule neurons and increases adult hippocampal neurogenesis. Average daily running distance typically increases over a period of 3 weeks in rodents. Whether neurogenesis and cell activation are greater at the peak of running as compared to the initial escalation period is not known. Therefore, adult C57BL/6J male mice received 5 days of BrdU injections, at the same age, to label dividing cells during the onset of wheel access or after 21 days during peak levels of running or in sedentary conditions. Mice were sampled either 24h or 25 days after the last BrdU injection to measure cell proliferation and survival, respectively. Immunohistochemistry was performed on brain sections to identify the numbers of proliferating BrdU-labeled cells, and new neurons (BrdU/NeuN co-labeled) in the dentate gyrus. Ki67 was used as an additional mitotic marker. The induction of c-Fos was used to identify neurons activated from running. Mice ran approximately half as far during the first 5 days as compared to after 21 days. Running increased Ki67 cells at the onset but after 21 days levels were similar to sedentary. Numbers of BrdU cells were similar in all groups 24h after the final injection. However, after 25 days, running approximately doubled the survival of new neurons born either at the onset or peak of running. These changes co-varied with c-Fos expression. We conclude that sustained running maintains a stable rate of neurogenesis above sedentary via activity-dependent increases in differentiation and survival, not proliferation, of progenitor cells in the C57BL/6J model.

Effects of western diet and wheel access on lipid profiles in mice selectively bred for high voluntary wheel running

Increased consumption of high‐fat foods and a sedentary lifestyle are viewed as two key factors in the ongoing trends for increased rates of human obesity and cardiovascular disease. However, in experimental studies with both humans and rodents, both diet and exercise have shown varying effects on metabolic syndrome risk factors, sometimes depending on genetic background. To examine potential interactive effects of diet, exercise, and genetic background on components of the metabolic syndrome, we studied mice bred for high voluntary wheel running and their respective controls. A standard chow (14% kcal from fat) or Western diet (WD, 42% kcal from fat plus added sucrose) was given to male mice housed with or without wheels for 60 days starting at 24 days of age. Neither genetic selection history nor wheel access had an appreciable impact on the final blood lipid profile. WD was obesogenic for both HR and C, leading to increased retroperitoneal fat and liver mass, even after accounting for wheel running and calories consumed. As expected from results of previous studies with diets high in saturated fats, WD also decreased plasma triglyceride levels. WD significantly increased fasting glucose levels, but raised total and HDL cholesterol concentrations, leading to an improved total/HDL ratio, which may offset some of the negative aspects of the diet. Supported by MSU Seed Grant to JCE and NSF IOB‐0543429 to TG

Exercise is Associated with Increased Drug‐Taking in Rats that Self‐Administer Methamphetamine at Low Levels

ObjectiveAbout 1% of young adults in the U.S. report using methamphetamine (METH) within the past year. Although METH is commonly used at dance parties, little is known about how physical activity influences use. Experiments were conducted to determine the relationship between voluntary exercise and METH self‐administration.MethodsRats were trained to self‐administer METH in chambers that contained both drug self‐administration apparatus and a running wheel. Rats were initially trained to self‐administer METH without wheel access. Once performance stabilized, rats were permitted access to the running wheel and the METH‐reinforced response lever concurrently.ResultsRats self‐administered METH at low levels prior to wheel access and the mean number of drug infusions taken during each session more than tripled after wheel‐access was permitted. Wheel running was stable within individual across sessions. The number of responses on the inactive lever was not significantly related to the dose of METH.ConclusionsIn these experiments, voluntary exercise was associated with increased METH self‐administration in rats that had previously demonstrated low levels of drug self‐administration. These results suggest that reinforcer competition is not the sole factor mediating effects of exercise on drug self‐administration. Research supported by National Institute of Drug Abuse grant R01 DA024705.

Wheel Access Does Not Attenuate Weight Gain in Mice Fed High-Fat or High-CHO Diets

To determine the effect of a high-fat or high-carbohydrate diet and running wheel activity on body composition, body mass, and caloric intake in C57Bl/6 mice. At 4 wk of age, five groups of C57Bl/6 mice were housed individually. Two groups had running wheels, whereas the other three groups did not. Within the running wheel groups, FAT-W consumed a high-fat diet (60.3% fat) and CHO-W consumed a high-carbohydrate diet (70.4% carbohydrate). Within the nonrunning groups, FAT consumed the high-fat diet, CHO consumed the high-carbohydrate diet, and the fifth group consumed standard chow. All groups consumed food ad libitum and were exposed to their respective conditions for 12 wk. Wheel activity, food consumption, body mass (BM), and percentage of body fat (%BF) were recorded. There was no significant difference in %BF or BM at the end of 12 wk between FAT-W and FAT or between CHO-W and CHO (P > 0.05). %BF was significantly higher in both FAT-W (42.9% +/- 0.6%) and FAT (45.9% +/- 0.8%) compared with CHO-W (30.8% +/- 1.4%) or CHO (33.4% +/- 1.0%; P < 0.001). BM was significantly higher in both FAT-W (42.8 +/- 0.7 g) and FAT (44.7 +/- 1.2 g) compared with either CHO-W (32.8 +/- 1.6 g) or CHO (37.1 +/- 0.8; P < 0.01). There was no difference in wheel activity between FAT-W and CHO-W (P > 0.05). Daily caloric intake was higher in both FAT-W (17.0 +/- 0.8 kcal) and FAT (15.9 +/- 0.9 kcal) compared with that in CHO-W (13.9 +/- 0.7 kcal) and CHO (13.6 +/- 0.5 kcal; P < 0.01). Access to a running wheel had no protective effect on BM or %BF in C57Bl/6 mice that consumed either a high-fat or a high-carbohydrate diet during a 12-wk period. Access to a running wheel did not affect caloric intake; however, average daily caloric intake was higher in mice on high-fat diets compared with that in mice on a high-carbohydrate diet.

Reduction of extinction and reinstatement of cocaine seeking by wheel running in female rats

Previous work has shown that wheel running reduced the maintenance of cocaine self-administration in rats. In the present study, the effect of wheel running on extinction and reinstatement of cocaine seeking was examined. Female rats were trained to run in a wheel during 6-h sessions, and they were then catheterized and placed in an operant conditioning chamber where they did not have access to the wheel but were allowed to self-administer iv cocaine. Subsequently, rats were divided into four groups and were tested on the extinction and reinstatement of cocaine seeking while they had varying access to a wheel in an adjoining compartment. The four groups were assigned to the following wheel access conditions: (1) wheel running during extinction and reinstatement (WER), (2) wheel running during extinction and a locked wheel during reinstatement (WE), (3) locked wheel during extinction and wheel running during reinstatement (WR), and (4) locked wheel during extinction and reinstatement (WL). WE and WR were retested later to examine the effect of one session of wheel access on cocaine-primed reinstatement. There were no group differences in wheel revolutions, in rate of acquisition of cocaine self-administration, or in responding during maintenance when there was no wheel access. However, during extinction, WE and WER responded less than WR and WL. WR and WER had lower cocaine-primed reinstatement than WE and WL. One session of wheel exposure in WE also suppressed cocaine-primed reinstatement. Wheel running immediately and effectively reduced cocaine-seeking behavior, but concurrent access to running was necessary. Thus, exercise is a useful and self-sustaining intervention to reduce cocaine-seeking behavior.

Chromosomal mapping of excessive physical activity in mice in response to a restricted feeding schedule

Excessive physical activity plays an important role in the progression of anorexia nervosa (AN) by accelerating weight loss during dietary restriction. To search for mechanisms underlying this trait, a panel of mouse chromosome substitution strains derived from C57BL/6J and A/J strains was exposed to a scheduled feeding paradigm and to voluntary running wheel (RW) access. Here, we showed that A/J chromosomes 4, 12 and 13 contribute to the development of a disrupted RW activity in response to daily restricted feeding. This pattern is characterized by intense RW activity during the habitual rest phase and leads to accelerated body weight loss. Regions on mouse chromosomes 4, 12 and 13 display homology with regions on human chromosomes linked with anxiety and obsessionality in AN cohorts. Therefore, our data open new roads for interspecies genetic studies of AN and for unraveling novel mechanisms and potential effective treatment strategies for these neurobehavioral traits.

Sexually dimorphic effects of postnatal treatment on the development of activity‐based anorexia in adolescent and adult rats

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a marked feature of anorexia nervosa. Using a modified version of the activity-based animal model of anorexia nervosa, we examine whether factors known to affect HPA axis activity influence the development of activity-based anorexia (ABA). Male and female rats were subjected to maternal separation or handling procedures during the first two postnatal weeks and tested in a mild version of the ABA paradigm, comprised of 2-hr daily running wheel access followed by 1-hr food access, either in adolescence or adulthood. Compared to handled females, maternally separated females demonstrated greater increases in wheel running and a more pronounced running-induced suppression of food intake during adolescence, but not in adulthood. In contrast, it was only in adulthood that wheel running produced more prolonged anorexic effects in maternally separated than in handled males. These findings highlight the interplay between early postnatal treatment, sex of the animal, and developmental age on running, food intake, and rate of body weight loss in a mild version of the ABA paradigm.

Lipid peroxidation and antioxidant status in rat: effect of food restriction and wheel running

Using the activity-based anorexia model, the aim of this investigation was to explore antioxidant enzyme activity (catalase, superoxide dismutase), total antioxidant status (TAS), and alpha-tocopherol in blood, liver, and gastrocnemius muscle associated with the food restriction and voluntary wheel running during 8 days. In addition, lipid peroxidation was measured by measurements of malondialdehyde (MDA). Wistars rats (n = 56) were randomly assigned to one of four groups: an ad lib sedentary group, a control wheel activity group, a food restriction-induced hyperactivity group (1 h/day ad lib food, 23 h/day ad lib wheel access), and a food-restricted sedentary group. The animals were killed when the rats in the food-restricted group had lost 25% of their free feeding weight. Antioxidant enzyme activities and TAS in blood, liver, and gastrocnemius muscle were unaffected by voluntary wheel running. A wheel activity effect (P < 0.05) was obtained for the MDA concentrations in plasma, with lower concentrations in trained animals. Food restriction effects were obtained for antioxidant capacity in liver, as well as for CAT activity in the gastrocnemius muscle and plasma MDA concentrations with lower values in the restricted animals. On the other hand, the food-restricted rats showed higher plasma TAS concentrations (P < 0.05) and higher alpha-tocopherol concentrations in the liver (P < 0.05) when compared to animals fed ad libitum. Our results also showed that food restriction coupled to wheel running decreased antioxidant parameters in liver, and plasmatic MDA concentrations and increased TAS plasma concentrations when compared to the ad libitum sedentary situation.

Chlorpromazine specifically prevents the wheel-induced feeding suppression in rats

In rats, limited daytime wheel access suppresses feeding over the subsequent night [Lattanzio SB, Eikelboom R. Wheel access duration in rats: I. effects on feeding and running. Behav Neurosci 2003; 117:496–504.]. This phenomenon is known as the wheel-induced feeding suppression (WIFS). The classic antipsychotic, chlorpromazine, can minimize the severity of the related activity anorexia procedure, but is thought to act through a suppression of running [Routtenberg A. “Self-starvation” of rats living in activity wheels: adaptation effects. J Comp Physiol Psychol 1968; 66:234–8.]. We tested the effects of chlorpromazine (2 mg/kg IP) on the acute WIFS in 40 adult male rats by administering the drug before or after 3 h of daytime wheel access and measuring food consumption over the subsequent 24 h. Control groups received saline injections or were exposed to locked wheels. While chlorpromazine did not attenuate feeding or change wheel running alone, it blocked their interaction, the acute WIFS. This procedure might be useful in screening drugs for anorexia nervosa where exercise is often elevated and feeding is suppressed.

Altered dopaminergic profiles: Implications for the regulation of voluntary physical activity

The biological regulating factors of physical activity in animals are not well understood. This study investigated differences in the central mRNA expression of seven dopamine genes ( Drd1, Drd2, Drd3, Drd4, Drd5, TH, and DAT) between high active C57/LJ ( n = 17) male mice and low active C3H/HeJ ( n = 20) male mice, and between mice with access to a running wheel and without running wheel access within strain. Mice were housed with running wheels interfaced with a computer for 21 days with distance and duration recorded every 24 h. On day 21, the striatum and nucleus accumbens were removed during the active period (∼9 pm) for dopaminergic analysis. On average, the C57L/J mice with wheels ran significantly farther (10.25 ± 1.37 km/day vs. 0.01 ± 0.09 km/day, p < 0.001), longer (329.73 ± 30.52 min/day vs. 7.81 ± 6.32 min/day, p < 0.001), and faster (31.27 ± 3.13 m/min vs. 11.81 ± 1.08 m/min, p < 0.001) than the C3H/HeJ mice with wheels over the 21 day period. No differences in gene expression were found between mice in either strain with wheels and those without wheels suggesting that access to running wheels did not alter dopaminergic expression. In contrast, relative expression for two dopamine genes was significantly lower in the C57L/J mice compared to the C3H/HeJ mice. These results indicate that decreased dopaminergic functioning is correlated with increased activity levels in C57L/J mice and suggests that D1-like receptors as well as tyrosine hydroxylase (an indicator of dopamine production), but not D2-like receptors may be associated with the regulation of physical activity in inbred mice.

High-fat diet offsets the long-lasting effects of a four-week running wheel access on food intake and body weight in OLETF rats

High-fat diet offsets the long-lasting effects of a four-week running wheel access on food intake and body weight in OLETF rats

The effects of prior weight reduction on the running wheel-induced feeding suppression in rats

Adult male rats given ad lib access to food and a running wheel show an initial feeding and weight suppression. Over 6-10 days feeding recovers, but body weight remains low. It is not clear which effect is primary, the wheel-induced feeding or weight change. To test this, rats were first restricted to 15g of food a day for 8 or 16 days to reduce their weight relative to control non-restricted rats. They were then returned to ad lib feeding and half the restricted and non-restricted control rats were introduced to the wheel either immediately (Experiment 1) or 4 days later (Experiment 2). Food intake, body weight, and wheel running were monitored throughout the experiments. At the return to ad lib feeding, prior food restriction elevated feeding. Both immediate and delayed wheel access suppressed feeding in both groups of wheel access rats compared to the appropriate control rats. Feeding history did not have a significant effect on wheel running. The wheel-induced reductions in feeding from baseline were similar in the weight reduced and normal weight animals suggesting that prior weight restriction did not prevent the onset of the wheel-induced feeding suppression. It is therefore suggested that the feeding suppression is not driven by a reduced weight set point.

Social dominance rank influences wheel running behavior in mice

Dominance hierarchies within social groups determine resource distribution. Resources, such as food and access to mating partners, can act as reinforcers. The present study examined the effect of social rank on access to wheel running—a reinforcing behavior performed by laboratory animals. Mice were identified as dominant or subordinate and given access to a running wheel access under solitary or social conditions. In the solitary condition, subordinate and dominant mice spent equal amounts of time on the running wheel. In the social condition, when one wheel was present, subordinate mice spent less time on the wheel than did dominant mice. Conversely, when two wheels were present, subordinates spent more time on the wheel than did dominant mice. When mice were given 24 h access to one running wheel in the social condition, dominant mice ran more than subordinates during the dark cycle. Subordinate mice did not compensate for the lack of running wheel access by schedule shifting. These results suggest that social rank influences access to reinforcers by behavioral interference rather than by social inhibition.

Effects of environmental enrichment on the amyotrophic lateral sclerosis mouse model

The manner in which an animal's environment is furnished may have significant implications for animal welfare as well as research outcomes. We evaluated four different housing conditions to determine the effects of what has been considered standard rodent enrichment and the exercise opportunities those environments allow on disease progression in the amyotrophic lateral sclerosis mouse model. Forty-eight copper/zinc superoxide dismutase mice (strain: B6SJL-TgN [SOD1-G931]1Gur) (SOD1) and 48 control (C) (strain: B6SJL-TgN[SOD1]2Gur) male mice were randomly assigned to four different conditions where 12 SOD1 and 12 C animals were allotted to each condition (n = 96). Conditions tested the effects of standard housing, a forced exercise regime, access to a mouse house and opportunity for ad libitum exercise on a running wheel. In addition to the daily all-occurrence behavioural sampling, mice were weighed and tested twice per week on gait and Rotor-Rod performance until the mice reached the age of 150 days (C) or met the criteria for our humane endpoint (SOD1). The SOD1 mice exposed to the forced exercise regime and wheel access did better in average lifespan and Rotor-Rod performance, than SOD1 mice exposed to the standard cage and mouse house conditions. In SOD1 mice, stride length remained longest throughout the progression of the disease in mice exposed to the forced exercise regime compared with other SOD1 conditions. Within the control group, mice in the standard cage and forced exercise regime conditions performed significantly less than the mice with the mouse house and wheels on the Rotor-Rod. Alpha motor neuron counts were highest in mice with wheels and in mice exposed to forced exercise regime in both mouse strains. All SOD1 mice had significantly lower alpha neuron counts than controls (P < 0.05). These data show that different enrichment strategies affect behaviour and disease progression in a transgenic mouse model, and may have implications for the effects of these strategies on experimental outcomes.

Epigenetic Effects on Integration of Limb Lengths in a Mouse Model: Selective Breeding for High Voluntary Locomotor Activity

Mammals exhibit a similar pattern of integration among homologous limb elements, the strength of which is believed to vary in response to selection for functional coordination or similarity. Although integration is hypothesized to primarily reflect the effect of genes intrinsic to limbs, extrinsic genetic or epigenetic factors may also affect the strength of integration through their impact on the magnitude and direction of skeletal variance or covariance. Such factors as neuromuscular coordination or bone-muscle interactions may therefore play a role in both canalization and the structure or magnitude of limb integration. If this were the case, then increased levels of locomotor activity would be predicted to increase canalization and the magnitude of covariation between limbs. To investigate whether postnatal activity levels can have a significant effect on variance within or covariance among homologous limb elements, we compared four groups of male mice from a long-term selective breeding experiment: (1) mice from lines bred for increased voluntary activity on running wheels and allowed free access to a wheel for 8 weeks beginning at weaning (“active”), (2) selected mice that did not have wheel access (“sedentary”), (3) active mice from non-selected control lines, and (4) sedentary control mice. Mice from selected lines that had wheel access ran significantly more than control-line mice. However, when controlled for activity, linetype, and body mass, results indicate few significant differences in means, variance, or covariation structure, and no significant differences in integration between limbs, suggesting that postnatal activity levels do not significantly affect canalization or integration of limb lengths. A possible explanation for this result is that whereas baseline levels of postnatal activity may help to maintain patterns of variance and integration, increased levels of activity do not further increase these measures. Investigations into disrupted epigenetic processes (e.g., via models in which neuromuscular coordination is impaired) are required to further test hypotheses about how canalization or integration of limb variation is affected by epigenetic factors.

Behavioral Despair and Home-Cage Activity in Mice with Chronically Elevated Baseline Corticosterone Concentrations

Dysfunction of the hypothalamic-pituitary-adrenal axis resulting in elevated baseline glucocorticoid concentrations is a hallmark of stress-related human anxiety and affective disorders, including depression. Mice from four replicate lines bred for high voluntary wheel running (HR lines) run almost three times as much as four non-selected control (C) lines, and exhibit two fold elevated baseline circulating corticosterone levels throughout the 24 h cycle. Although elevated baseline CORT may be beneficial for high locomotor activity, chronic elevations can have deleterious effects on multiple systems, and may predispose for affective disorders. Because stressful events often precede a depressive bout, we quantified depressive-like behavior in the forced-swim (FST; generation 41) and tail-suspension tests (TST; generation 47) in HR and C mice that had wheel access for 6 days and then were deprived of wheels on day seven prior to the FST or TST. Male HR spent significantly more time immobile in the FST than C, suggesting that HR males have a predisposition for depression-like behavior. Both male and female HR (generation 43) were more active than same-sex controls in both wheel running and home-cage activity across 22 h (pooling the sexes, HR/C = 2.28 and 2.66, respectively).

Phenotypic plasticity and experimental evolution

There were two errors published in J. Exp. Biol. 209, 2344-2361.First, on p. 2355 in the first complete paragraph of the section entitled`Plasticity of exercise-related traits', the authors stated:If we imagine further that S and C mice housed without wheels showed no difference (or at least values similar to those of C mice housed with wheels),then the S mice seem to be more responsive to wheel exposure, i.e. they are more plastic.The sentence should have read:If we imagine further that S and C mice housed without wheels showed values similar to those of C mice housed with wheels, then the S mice seem to be more responsive to wheel exposure, i.e. they are more plastic.Second, on pp. 2355–2356, beginning in column 2 of p. 2355, the authors stated:For hematocrit in females, Table 2 shows that the ln likelihood of the nested ANCOVA model without wheel running (–75.7) is larger (less negative, in this case) than for the model with wheel running (–83.7). As the latter model contains one additional parameter (estimating the effect of wheel running), twice the difference in ln likelihoods (16.0, in this case)can be compared with a χ2 distribution with one degree of freedom, for which the critical value for P=0.05 is 3.841. Therefore,the model with wheel running as an additional covariate yields a significantly worse fit to the data, and we conclude that the difference in hematocrit between S and C mice when housed with wheel access is not best explained as a simple function of the greater running by S mice.The paragraph should have read:For hematocrit in females, Table 2 shows that the ln likelihood of the nested ANCOVA model without wheel running is –78.1 whereas for the model with wheel running it is –77.9. As the latter model contains one additional parameter (estimating the effect of wheel running), twice the difference in ln likelihoods (0.3 in this case) can be compared with aχ 2 distribution with one degree of freedom, for which the critical value for P=0.05 is 3.841. Therefore, the model with wheel running as an additional covariate does not fit the data significantly better,and we conclude that the difference in hematocrit between S and C mice when housed with wheel access is not best explained as a simple function of the greater running by S mice.We apologise to the authors and readers for these errors but do not believe that they compromise the overall results and conclusions of the paper.

Basal Metabolic Rate of Aged Mice Is Affected by Random Genetic Drift But Not by Selective Breeding for High Early‐Age Locomotor Activity or Chronic Wheel Access

The study of correlated evolution can lead to new insights about the inheritance patterns of complex traits. In order to better understand the evolution of metabolic rate, we tested whether voluntary activity levels and basal metabolic rate are genetically correlated in 90-wk-old mice (Mus domesticus) from replicated lines of the sixteenth generation of an artificial selection experiment for high early-age wheel-running activity. We measured basal rates of oxygen consumption and carbon dioxide production and also computed the respiratory exchange ratio. Half of the individuals from both selected and control lines had been allowed free access to running wheels since 4 wk of age, while the other half were in standard cages. This design allowed testing of hypotheses about (1) genetic correlations between voluntary activity and metabolic rate and (2) lifetime training effects on metabolic traits. Selection group did not have a significant effect on metabolic traits; therefore, this study does not support some of the implicit assumptions of the aerobic capacity model for the evolution of vertebrate energetics. Activity group also did not affect metabolic rate, indicating that lifetime training does not alter basal metabolism in these mice. However, strong replicate line-within-selection-group differences were detected, indicating the occurrence of random genetic drift. In females, this divergence in metabolic traits attributable to drift was independent of body mass, but in males it was probably caused by a correlated response to selection involving body mass. This study is the first to show such effects of random genetic drift on metabolic traits.