Biomedical subjects

Theodore Garland

Publications and source records attributed to Theodore Garland.

At least 19 recordsLinked to original sources

PubMed2006

Baseline and stress-induced plasma corticosterone concentrations of mice selectively bred for high voluntary wheel running.

The hypothalamic-pituitary-adrenal (HPA) axis is important in regulating energy metabolism and in mediating responses to stressors, including increasing energy availability during physical exercise. In addition, glucocorticoids act directly on the central nervous system and influence behavior, including locomotor activity. To explore potential changes in the HPA axis as animals evolve higher voluntary activity levels, we characterized plasma corticosterone (CORT) concentrations and adrenal mass in four replicate lines of house mice that had been selectively bred for high voluntary wheel running (HR lines) for 34 generations and in four nonselected control (C) lines. We determined CORT concentrations under baseline conditions and immediately after exposure to a novel stressor (40 min of physical restraint) in mice that were housed without access to wheels. Resting daytime CORT concentrations were approximately twice as high in HR as in C mice for both sexes. Physical restraint increased CORT to similar concentrations in HR and C mice; consequently, the proportional response to restraint was smaller in HR than in C animals. Adrenal mass did not significantly differ between HR and C mice. Females had significantly higher baseline and postrestraint CORT concentrations and significantly larger adrenal glands than males in both HR and C lines. Replicate lines showed significant variation in body mass, length, baseline CORT concentrations, and postrestraint CORT concentrations in one or both sexes. Among lines, both body mass and length were significantly negatively correlated with baseline CORT concentrations, suggesting that CORT suppresses growth. Our results suggest that selection for increased locomotor activity has caused correlated changes in the HPA axis, resulting in higher baseline CORT concentrations and, possibly, reduced stress responsiveness and a lower growth rate.

Adrenal Glands↗

PubMed2006

Sexual size dimorphism in a Drosophila clade, the D. obscura group.

The Drosophila obscura clade consists of about 41 species, of which 20 were used for analyses of wing and thorax length. Our primary goal was to investigate the magnitude of sexual size dimorphism (SSD) of these traits within this clade and to test Rensch's Rule [when females are larger than males, SSD (e.g., female/male ratio) should decrease with body size]. Our secondary goal was methodological and involved evaluating for these flies alternative measures of SSD (female/male ratio, female/male absolute difference, female/male relative difference), developing a bootstrap method to estimate the magnitude of intraspecific variation in SSD, and applying a new method of estimating allometric relationships that is phylogenetically based and incorporates error variance in both traits. All indices of SSD were strongly correlated for both size traits. Nevertheless, female/male ratio is the best index here: it is easily interpretable and essentially independent of size. For both traits, SSD (F/M) varied interspecifically, showed a strong phylogenetic signal, but did not differ for the main phylogenetic subgroups or correlate with latitude. Factors underlying variation in SSD in this clade are elusive and might include genetic drift. SSD (wing) tended to decrease with increasing size, as predicted by Rensch's Rule, though not consistently so. SSD (thorax) was unrelated to size. However, analysis of published data for thorax length of Drosophila spp. (N=42) with a larger size range showed that SSD decreased significantly with increasing size (consistent with Rensch's Rule), suggesting our ability to detect SSD-size relations in the D. obscura data may be limited by low statistical power.

Animals↗

PubMed2006

Wheel-running activity and energy metabolism in relation to ambient temperature in mice selected for high wheel-running activity.

Interrelationships between ambient temperature, activity, and energy metabolism were explored in mice that had been selectively bred for high spontaneous wheel-running activity and their random-bred controls. Animals were exposed to three different ambient temperatures (10, 20 and 30 degrees C) and wheel-running activity and metabolic rate were measured simultaneously. Wheel-running activity was decreased at low ambient temperatures in all animals and was increased in selected animals compared to controls at 20 and 30 degrees C. Resting metabolic rate (RMR) and daily energy expenditure (DEE) decreased with increasing ambient temperature. RMR did not differ between control and selected mice, but mass-specific DEE was increased in selected mice. The cost of activity (measured as the slope of the relationship between metabolic rate and running speed) was similar at all ambient temperatures and in control and selected mice. Heat generated by running apparently did not substitute for heat necessary for thermoregulation. The overall estimate of running costs was 1.2 kJ/km for control mice and selected mice.

Animals↗

PubMed2006

Maximal oxygen consumption in relation to subordinate traits in lines of house mice selectively bred for high voluntary wheel running.

We studied relations between maximal O2 consumption (VO2 max) during forced exercise and subordinate traits associated with blood O2 transport and cellular respiration in four lines of mice selectively bred for high voluntary wheel running (S lines) and their four nonselected control (C) lines. Previously, we reported VO2 max of 59 females at three Po2 (hypoxia = 14% O2, normoxia = 21%, hyperoxia = 30%). Here, we test the hypothesis that variation in VO2 max can be explained, in part, by hemoglobin concentration and Po2 necessary to obtain 50% O2 saturation of Hb (an estimate of Hb affinity for O2) of the blood as well as citrate synthase activity and myoglobin concentration of ventricles and gastrocnemius muscle. Statistical analyses controlled for body mass, compared S and C lines, and also considered effects of the mini-muscle phenotype (present only in S lines and resulting from a Mendelian recessive allele), which reduces hindlimb muscle mass while increasing muscle mass-specific aerobic capacity. Although S lines had higher VO2 max than C, subordinate traits showed no statistical differences when the presence of the mini-muscle phenotype was controlled. However, subordinate traits did account for some of the individual variation in VO2 max. Ventricle size was a positive predictor of VO2 max at all three Po2. Blood Hb concentration was a positive predictor of VO2 max in S lines but a negative predictor in C lines, indicating that the physiological underpinnings of VO2 max have been altered by selective breeding. Mice with the mini-muscle phenotype had enlarged ventricles, with higher mass-specific citrate synthase activity and myoglobin concentration, which may account for their higher VO2 max in hypoxia.

Animals↗

PubMed2006

AMP-activated protein kinase is involved in endothelial NO synthase activation in response to shear stress.

OBJECTIVE: The regulation of AMP-activated protein kinase (AMPK) is implicated in vascular biology because AMPK can phosphorylate endothelial NO synthase (eNOS). In this study, we investigate the regulation of the AMPK-eNOS pathway in vascular endothelial cells (ECs) by shear stress and the activation of aortic AMPK in a mouse model with a high level of voluntary running (High-Runner). METHODS AND RESULTS: By using flow channels with cultured ECs, AMPK Thr172 phosphorylation was increased with changes of flow rate or pulsatility. The activity of LKB1, the upstream kinase of AMPK, and the phosphorylation of eNOS at Ser1179 were concomitant with AMPK activation responding to changes in flow rate or pulsatility. The blockage of AMPK by a dominant-negative mutant of AMPK inhibited shear stress-induced eNOS Ser1179 phosphorylation and NO production. Furthermore, aortic AMPK activity and level of eNOS phosphorylation were significantly elevated in the aortas of High-Runner mice. CONCLUSIONS: Our results suggest that shear stress activates AMPK in ECs, which contributes to elevated eNOS activity and subsequent NO production. Hence, AMPK, in addition to serving as an energy sensor, also plays an important role in regulating vascular tone.

AMP-Activated Protein Kinases↗

PubMed2006

Morphometry, ultrastructure, myosin isoforms, and metabolic capacities of the "mini muscles" favoured by selection for high activity in house mice.

Prolonged selective breeding of mice (Mus musculus) for high levels of voluntary wheel running has favoured an unusual phenotype ("mini muscles"), apparently caused by a single Mendelian recessive allele, in which most hind-limb muscles are markedly reduced in mass, but have increased mass-specific activities of mitochondrial enzymes. We examined whether these changes reflect changes in fibre size, number or ultrastructure in normal and "mini-muscle" mice within the two (of four) selectively bred lines (lab designations L3 and L6) that exhibit the phenotype at generations 26 and 27. In both lines, the gastrocnemius and plantaris muscles are smaller in mass (by >50% and 20%, respectively) in affected individuals. The mass-specific activities of mitochondrial enzymes in the gastrocnemius and plantaris muscles were increased in the mini phenotype in both lines, with stronger effects in the gastrocnemius muscle. In the gastrocnemius, the % myosin heavy chain (MHC) IIb was reduced by 50% in L3 and by 30% in L6, whereas the % MHC IIa and I were higher, particularly in L3. Fibre number in the plantaris muscle did not significantly differ between mini and normal muscles, although muscle mass was a significant positive correlate of fibre number. Small fibres were more abundant in mini than normal muscles in L3. Mitochondrial volume density was significantly higher in mini than normal muscle fibres in L3, but not in L6. Microscopy revealed a surprising attribute of the mini muscles: an abundance of small, minimally differentiated, myofibril-containing cells positioned in a disorderly fashion, particularly in the surface layer. We hypothesise that these unusual cells may be satellite cells or type IIb fibres that did not complete their differentiation. Together, these observations suggest that mice with the mini phenotype have reduced numbers of type IIb fibres in many of their hind-limb muscles, leading to a decrease in mass and an increase in mass-specific aerobic capacity in muscles that typically have a high proportion of type IIb fibres. Moreover, the several statistically significant interactions between muscle phenotype and line indicate that the effect of the underlying allele is altered by genetic background.

Alleles↗

PubMed2006

Experimental evolution and phenotypic plasticity of hindlimb bones in high-activity house mice.

Studies of rodents have shown that both forced and voluntary chronic exercise cause increased hindlimb bone diameter, mass, and strength. Among species of mammals, "cursoriality" is generally associated with longer limbs as well as relative lengthening of distal limb segments, resulting in an increased metatarsal/femur (MT/F) ratio. Indeed, we show that phylogenetic analyses of previously published data indicate a positive correlation between body mass-corrected home range area and both hindlimb length and MT/F in a sample of 19 species of Carnivora, although only the former is statistically significant in a multiple regression. Therefore, we used an experimental evolution approach to test for possible adaptive changes (in response to selective breeding and/or chronic exercise) in hindlimb bones of four replicate lines of house mice bred for high voluntary wheel running (S lines) for 21 generations and in four nonselected control (C) lines. We examined femur, tibiafibula, and longest metatarsal of males housed either with or without wheel access for 2 months beginning at 25-28 days of age. As expected from previous studies, mice from S lines ran more than C (primarily because the former ran faster) and were smaller in body size (both mass and length). Wheel access reduced body mass (but not length) of both S and C mice. Analysis of covariance (ANCOVA) revealed that body mass was a statistically significant predictor of all bone measures except MT/F ratio; therefore, all results reported are from ANCOVAs. Bone lengths were not significantly affected by either linetype (S vs. C) or wheel access. However, with body mass as a covariate, S mice had significantly thicker femora and tibiafibulae, and wheel access also significantly increased diameters. Mice from S lines also had heavier feet than C, and wheel access increased both foot and tibiafibula mass. Thus, the directions of evolutionary and phenotypic adaptation are generally consistent. Additionally, S-line individuals with the mini-muscle phenotype (homozygous for a Mendelian recessive allele that halves hindlimb muscle mass [Garland et al., 2002, Evolution 56:1,267-1,275]) exhibited significantly longer and thinner femora and tibiafibulae, with no difference in bone masses. Two results were considered surprising. First, no differences were found in the MT/F ratio (the classic indicator of cursoriality). Second, we did not find a significant interaction between linetype and wheel access for any trait, despite the higher running rate of S mice.

Animals↗

PubMed2006

Artificial selection for increased maternal defense behavior in mice.

Maternal aggression is directed towards intruders by lactating females and is critical for defense of offspring. Within-family selection for increased maternal defense in outbred house mice (Mus domesticus; Hsd:ICR strain) was applied to one selected (S) line, using total duration of attacks in a 3-min test as the selection criterion. One control (C) line was maintained and both lines were propagated by 13 families in each generation. Prior to selection, heritability of maternal aggression was estimated to be 0.61 based on mother-offspring regression. Duration of attacks responded to selection with a mean realized heritability of 0.40 (corrected for within-family selection) after eight generations. At generation 5, the S and C line also differed significantly for litter size at birth and at mid-lactation (both lower in S), average individual pup mass at midlactation (higher in S), and pup retrieval latency (longer in S), but not for other maternal measures that we studied (e.g., dam mass). Additionally, number of entries to middle and closed plus maze compartments was significantly higher in S mice in Generation 5. This is the first study to select for high maternal defense and these mice will be made available as a tool for understanding the genetic and neural basis of maternal aggression.

Aggression↗

PubMed2006

Maximum aerobic performance in lines of Mus selected for high wheel-running activity: effects of selection, oxygen availability and the mini-muscle phenotype.

We compared maximum aerobic capacity during forced exercise (VO2max) in hypoxia (PO2=14% O2), normoxia (21%) and hyperoxia (30%) of lines of house mice selectively bred for high voluntary wheel running (S lines) with their four unselected control (C) lines. We also tested for pleiotropic effects of the ;mighty mini-muscle' allele, a Mendelian recessive that causes a 50% reduction in hind limb muscle but a doubling of mass-specific aerobic enzyme activity, among other pleiotropic effects. VO2max of female mice was measured during forced exercise on a motorized treadmill enclosed in a metabolic chamber that allowed altered PO2. Individual variation in VO2max was highly repeatable within each PO2, and values were also significantly correlated across PO2. Analysis of covariance showed that S mice had higher body-mass-adjusted VO2max than C at all PO2, ranging from +10.7% in hypoxia to +20.8% in hyperoxia. VO2max of S lines increased practically linearly with PO2, whereas that of C lines plateaued from normoxia to hyperoxia, and respiratory exchange ratio (=CO2 production/VO2max) was lower for S lines. These results suggest that the physiological underpinnings of VO2max differ between the S and C lines. Apparently, at least in S lines, peripheral tissues may sustain higher rates of oxidative metabolism if central organs provide more O2. Although the existence of central limitations in S lines cannot be excluded based solely on the present data, we have previously reported that both S and C lines can attain considerably higher VO2max during cold exposure in a He-O2 atmosphere, suggesting that limitations on VO2max depend on interactions between the central and peripheral organs involved. In addition, mini-muscle individuals had higher VO2max than did those with normal muscles, suggesting that the former might have higher hypoxia tolerance. This would imply that the mini-muscle phenotype could be a good model to test how exercise performance and hypoxia tolerance could evolve in a correlated fashion, as previous researchers have suggested.

Analysis of Variance↗

PubMed2006

Phenotypic plasticity and experimental evolution.

Natural or artificial selection that favors higher values of a particular trait within a given population should engender an evolutionary response that increases the mean value of the trait. For this prediction to hold, the phenotypic variance of the trait must be caused in part by additive effects of alleles segregating in the population, and also the trait must not be too strongly genetically correlated with other traits that are under selection. Another prediction, rarely discussed in the literature, is that directional selection should favor alleles that increase phenotypic plasticity in the direction of selection, where phenotypic plasticity is defined as the ability of one genotype to produce more than one phenotype when exposed to different environments. This prediction has received relatively little empirical attention. Nonetheless, many laboratory experiments impose selection regimes that could allow for the evolution of enhanced plasticity (e.g. desiccation trials with Drosophila that last for several hours or days). We review one example that involved culturing of Drosophila on lemon for multiple generations and then tested for enhanced plasticity of detoxifying enzymes. We also review an example with vertebrates that involves selective breeding for high voluntary activity levels in house mice, targeting wheel-running behavior on days 5+6 of a 6-day wheel exposure. This selection regime allows for the possibility of wheel running itself or subordinate traits that support such running to increase in plasticity over days 1-4 of wheel access. Indeed, some traits, such as the concentration of the glucose transporter GLUT4 in gastrocnemius muscle, do show enhanced plasticity in the selected lines over a 5-6 day period. In several experiments we have housed mice from both the Selected (S) and Control (C) lines with or without wheel access for several weeks to test for differences in plasticity (training effects). A variety of patterns were observed, including no training effects in either S or C mice, similar changes in both the S and C lines, greater changes in the S lines but in the same direction in the C lines, and even opposite directions of change in the S and C lines. For some of the traits that show a greater training effect in the S lines, but in the same direction as in C lines, the greater effect can be explained statistically by the greater wheel running exhibited by S lines ('more pain, more gain'). For others, however, the differences seem to reflect inherently greater plasticity in the S lines (i.e. for a given amount of stimulus, such as wheel running/day, individuals in the S lines show a greater response as compared with individuals in the C lines). We suggest that any selection experiment in which the selective event is more than instantaneous should explore whether plasticity in the appropriate (adaptive) direction has increased as a component of the response to selection.

Adaptation, Physiological↗

PubMed2006

Clostridial enteropathy in lactating outbred swiss-derived (ICR) mice.

Reports of severe enteric disease of unknown etiology affecting lactating mice have appeared in the literature. Clostridial disease similar to that seen in cattle and sheep on high-carbohydrate rations and caused by Clostridium perfringens has been suspected in these mouse outbreaks but has not been isolated from affected mice. The present report describes a severe, necrotizing enterocolitis associated with overgrowth of C. perfringens type A in lactating Swiss-derived (ND4) mice. Mice nursing large litters of pups in the second week of life were the most severely affected. The organism isolated from dead or moribund mice was positive by polymerase chain reaction assay for the gene for the C. perfringens a toxin, but actual toxin production was not determined. The disease in this mouse colony was ameliorated by increasing the fat and calorie content of the diet of lactating dams, which each received 1 g peanut butter every 48 h.

Animals↗

PubMed2005

Effects of size, sex, and voluntary running speeds on costs of locomotion in lines of laboratory mice selectively bred for high wheel-running activity.

Selective breeding for over 35 generations has led to four replicate (S) lines of laboratory house mice (Mus domesticus) that run voluntarily on wheels about 170% more than four random-bred control (C) lines. We tested whether S lines have evolved higher running performance by increasing running economy (i.e., decreasing energy spent per unit of distance) as a correlated response to selection, using a recently developed method that allows for nearly continuous measurements of oxygen consumption (VO2) and running speed in freely behaving animals. We estimated slope (incremental cost of transport [COT]) and intercept for regressions of power (the dependent variable, VO2/min) on speed for 49 males and 47 females, as well as their maximum VO2 and speeds during wheel running, under conditions mimicking those that these lines face during the selection protocol. For comparison, we also measured COT and maximum aerobic capacity (VO2max) during forced exercise on a motorized treadmill. As in previous studies, the increased wheel running of S lines was mainly attributable to increased average speed, with males also showing a tendency for increased time spent running. On a whole-animal basis, combined analysis of males and females indicated that COT during voluntary wheel running was significantly lower in the S lines (one-tailed P=0.015). However, mice from S lines are significantly smaller and attain higher maximum speeds on the wheels; with either body mass or maximum speed (or both) entered as a covariate, the statistical significance of the difference in COT is lost (one-tailed P> or =0.2). Thus, both body size and behavior are key components of the reduction in COT. Several statistically significant sex differences were observed, including lower COT and higher resting metabolic rate in females. In addition, maximum voluntary running speeds were negatively correlated with COT in females but not in males. Moreover, males (but not females) from the S lines exhibited significantly higher treadmill VO2max as compared to those from C lines. The sex-specific responses to selection may in part be consequences of sex differences in body mass and running style. Our results highlight how differences in size and running speed can account for lower COT in S lines and suggest that lower COT may have coadapted in response to selection for higher running distances in these lines.

Animals↗

PubMed2005

Contractile abilities of normal and "mini" triceps surae muscles from mice (Mus domesticus) selectively bred for high voluntary wheel running.

As reported previously, artificial selection of house mice caused a 2.7-fold increase in voluntary wheel running of four replicate selected lines compared with four random-bred control lines. Two of the selected lines developed a high incidence of a small-muscle phenotype ("mini muscles") in the plantar flexor group of the hindlimb, which apparently results from a simple Mendelian recessive allele. At generations 36-38, we measured wheel running and key contractile characteristics of soleus and medial gastrocnemius muscles from normal and mini muscles in mice from these selected lines. Mice with mini muscles ran faster and a greater distance per day than normal individuals but not longer. As expected, in mini-muscle mice the medial and lateral gastrocnemius muscles were approximately 54 and 45% the mass of normal muscles, respectively, but the plantaris muscles were not different in mass and soleus muscles were actually 30% larger. In spite of the increased mass, contractile characteristics of the soleus were unchanged in any notable way between mini and normal mice. However, medial gastrocnemius muscles in mini mice were changed markedly toward a slower phenotype, having slower twitches; demonstrated a more curved force-velocity relationship; produced about half the mass-specific isotonic power, 20-50% of the mass-specific cyclic work and power (only 10-25% the absolute power if the loss in mass is considered); and fatigued at about half the rate of normal muscles. These changes would promote increased, aerobically supported running activity but may compromise activities that require high power, such as sprinting.

Animal Husbandry↗

PubMed2005

Maximal metabolic rates during voluntary exercise, forced exercise, and cold exposure in house mice selectively bred for high wheel-running.

Selective breeding for high wheel-running activity has generated four lines of laboratory house mice (S lines) that run about 170% more than their control counterparts (C lines) on a daily basis, mostly because they run faster. We tested whether maximum aerobic metabolic rates (V(O2max)) have evolved in concert with wheel-running, using 48 females from generation 35. Voluntary activity and metabolic rates were measured on days 5+6 of wheel access (mimicking conditions during selection), using wheels enclosed in metabolic chambers. Following this, V(O2max) was measured twice on a motorized treadmill and twice during cold-exposure in a heliox atmosphere (HeO2). Almost all measurements, except heliox V(O2max), were significantly repeatable. After accounting for differences in body mass (S < C) and variation in age at testing, S and C did not differ in V(O2max) during forced exercise or in heliox, nor in maximal running speeds on the treadmill. However, running speeds and V(O2max) during voluntary exercise were significantly higher in S lines. Nevertheless, S mice never voluntarily achieved the V(O2max) elicited during their forced treadmill trials, suggesting that aerobic capacity per se is not limiting the evolution of even higher wheel-running speeds in these lines. Our results support the hypothesis that S mice have genetically higher motivation for wheel-running and they demonstrate that behavior can sometimes evolve independently of performance capacities. We also discuss the possible importance of domestication as a confounding factor to extrapolate results from this animal model to natural populations.

Age Factors↗

PubMed2005

Phylogenetic approaches in comparative physiology.

Over the past two decades, comparative biological analyses have undergone profound changes with the incorporation of rigorous evolutionary perspectives and phylogenetic information. This change followed in large part from the realization that traditional methods of statistical analysis tacitly assumed independence of all observations, when in fact biological groups such as species are differentially related to each other according to their evolutionary history. New phylogenetically based analytical methods were then rapidly developed, incorporated into ;the comparative method', and applied to many physiological, biochemical, morphological and behavioral investigations. We now review the rationale for including phylogenetic information in comparative studies and briefly discuss three methods for doing this (independent contrasts, generalized least-squares models, and Monte Carlo computer simulations). We discuss when and how to use phylogenetic information in comparative studies and provide several examples in which it has been helpful, or even crucial, to a comparative analysis. We also consider some difficulties with phylogenetically based statistical methods, and of comparative approaches in general, both practical and theoretical. It is our personal opinion that the incorporation of phylogeny information into comparative studies has been highly beneficial, not only because it can improve the reliability of statistical inferences, but also because it continually emphasizes the potential importance of past evolutionary history in determining current form and function.

Computer Simulation↗

PubMed2005

Muscle fiber-type variation in lizards (Squamata) and phylogenetic reconstruction of hypothesized ancestral states.

Previously, we found that phrynosomatid lizards, a diverse group common in the southwestern USA, vary markedly in fiber-type composition of the iliofibularis (a hindlimb muscle important in locomotion). Phrynosomatidae comprises three subclades: the closely related sand and horned lizards, and their relatives the Sceloporus group. The variation in muscle fiber-type composition for 11 phrynosomatid species is attributable mainly to differences between the sand- and horned-lizard subclades. Here, we expand the phrynosomatid database with three additional species and compare these results with data collected for 10 outgroup (distantly related) species. Our goal was to determine if the patterns found in Phrynosomatidae hold across a broader phylogenetic range of the extant lizards and to elucidate the evolution of muscle fiber-type composition and related traits. To allow for meaningful comparisons, data were collected from species that are primarily terrestrial and relatively small in size (3.5-65 g body mass). Results indicate that the fiber-type variation observed within the Phrynosomatidae almost spans the range of variation observed in our sample of 24 species from eight families. However, one species of Acanthodactylus (Lacertidae) had a consistent region of large tonic fibers (that did not stain darkly for either succinic dehydrogenase or myosin ATPase activity), a fiber-type only occasionally seen in the other 23 species examined. Many species have a large proportion of either fast-twitch glycolytic (FG; e.g. sand lizards and Aspidoscelis) or fast-twitch oxidative-glycolytic (FOG) fibers (e.g. horned lizards), with the slow-oxidative proportion occupying only 1-17% of the iliofibularis. Importantly, the negative relationship between FG and FOG composition observed in Phrynosomatidae appears to be a characteristic of lizards in general, and could lead to functional trade-offs in aspects of locomotor performance, as has previously been reported for Lacertidae. Reconstruction of ancestral trait values by use of phylogenetically based statistical methods indicates especially large changes in fiber-type composition during the evolution of horned lizards.

Animals↗

PubMed2005

Selective breeding for high endurance running increases hindlimb symmetry.

Comparative studies provide correlational evidence of morphological adaptations for high locomotor performance, such as the classical indicators of cursoriality in mammals, long limbs and high metatarsal/femur ratios. More recently, enlarged femoral condyles have been suggested as an adaptation for high endurance running in the genus Homo. Asymmetry of locomotor appendages should adversely affect locomotor abilities, but this has not been studied in a rigorous evolutionary context. We used experimental evolution to test for morphological adaptations associated with high voluntary wheel running in selectively bred lines of mice. Surprisingly, the classical indicators of cursoriality had not evolved in concert with high activity levels. Instead, high runners had larger femoral condyles and reduced directional asymmetry of hindlimb bones. We hypothesize that greater limb symmetry and larger femoral heads are general adaptations associated with sustained, high-speed locomotion.

Adaptation, Biological↗

PubMed2004

Opioid-mediated pain sensitivity in mice bred for high voluntary wheel running.

We tested the hypothesis that thermal tail-flick latency, a common measure of pain sensitivity in rodents, would be altered in lines of mice that had been selectively bred for high voluntary wheel-running behavior. Specifically, we predicted that the selected (High-Runner) lines would show decreased pain sensitivity relative to their control (C; randombred) lines, and would respond differently to drugs that block opioid receptors. We first compared tail-flick latency between High-Runner and C female mice during the day (no wheel access) and at night (with wheel access). Second, we compared effects of the opioid antagonist naloxone (10 mg/kg, i.p.) on tail-flick latency during the day (no wheel access). Third, we compared effects of naloxone (5 and 10 mg/kg, i.p.) and naltrexone, a longer-lasting opioid antagonist (0.1, 1, 5, 10, 50, and 100 mg/kg, i.p.), on voluntary wheel running. Tail-flick latencies were longer at night (when mice were active on wheels), but mice from High-Runner and C lines did not differ during the day or night. Administration of naloxone (10 mg/kg, i.p.) decreased tail-flick latency measured during the day, equally in High-Runner and C mice. Naloxone (5 and 10 mg/kg, i.p.) and high doses of naltrexone (50 and 100 mg/kg, i.p.) decreased wheel running equally in High-Runner and C mice. Further studies will be required to determine whether other types of pain sensitivity have also failed to evolve in association with increased voluntary wheel running.

Analysis of Variance↗