| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Zoology, University of Wisconsin-Madison, Madison, Wisconsin 53706
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Plasma levels of corticosterone (B) respond acutely to exercise in all mammals that have been studied, but the literature contains conflicting reports regarding how chronic activity alters this response. We measured acute and chronic effects of voluntary activity on B in a novel animal model, mice selectively bred for high voluntary wheel running. Female mice were housed with or without wheels for 8 wk beginning at 26 days of age. Wheel-access selection mice had significantly higher B at night 8, day 15, and night 29, compared with wheel-access controls. Elevation of B was an acute effect of voluntary exercise. When adjusted for running in the previous 20 min, no difference between wheel-access selection and control animals remained. No training effect on B response was observed. These results are among the strongest evidence that, in some animals, the acute B response is unaffected by chronic voluntary exercise. In mice without wheels, selection mice had significantly higher B than controls at day 15, night 29, and night 50, suggesting that selection resulted in a modulation of the hypothalamic-pituitary-adrenal axis. Growth over the first 4 wk of treatment was significantly and inversely related to average night B levels within each of the four treatment groups.
artificial selection; endurance training; evolution; glucocorticoids; growth; stress response
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
GLUCOCORTICOIDS PLAY AN IMPORTANT ROLE in the mobilization of energy reserves during physical activity by stimulating gluconeogenesis, promoting lipolysis of blood lipids, and increasing protein catabolism. A wide range of studies, in several species of mammals, have reported acute increases in the plasma concentration of glucocorticoids in response to submaximal (12, 30, 53), maximal (17, 32), and supramaximal (41, 43) exercise. Although the glucocorticoid response to light physical activity is variable, these previous studies have generally established that plasma glucocorticoid levels rise with moderate to exhaustive exercise and that higher exercise workloads elicit greater glucocorticoid response (16, 51).
The effect of chronic exercise on the glucocorticoid response to exercise is less clear (29). In studies of both humans and other mammals, researchers have reported increases (50, 52), decreases (53), and no change (6, 14) in the glucocorticoid response after training. Because forced-exercise training regimens are commonly employed to study endocrine responses in nonhuman animals (see Ref. 6), a confounding of the effects of exercise and psychological stress may contribute to the observed variation in training response. Chronic exposure to psychological stressors (novel environment or foot shock) failed to attenuate (42) or actually increased (22, 34) the glucocorticoid stress response in rats and mice, demonstrating that even lengthy habituation protocols may not adequately remove the psychological component of the stress response to forced exercise. Despite conflicting results, overall these studies suggest that physical training can affect the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis and that the effects of training vary with exercise type, intensity, and duration (51).
In addition to supporting activity via metabolic modulation, glucocorticoids also have complex effects in the central nervous system (54), including effects on locomotor behavior (2, 7, 11). For example, in captive screech owls, peaks in corticosterone corresponded with periods of high locomotor activity at the time of dispersal (3). In red-eared slider turtles (Trachemys scripta elegans), administration of exogenous corticosterone in physiological doses increased locomotor activity over the next 48 h (10). In rats, corticosterone was necessary for the occurrence of schedule-induced wheel running after adrenalectomy (33), and chronic corticosterone administration to intact animals resulted in increased locomotor activity (56). Corticosterone is also self-administered intravenously by catheterized rats (37) and thus is thought to have reinforcing properties. The self-reinforcing property may relate to the expression of "sensation-seeking behavior" (37) and perhaps also to the motivation for voluntary wheel running.
We have developed a novel mouse model to study the evolution of physiological traits that support increased levels of locomotor activity, including the role of glucocorticoids in voluntary exercise. After 24 generations of artificial selection for high voluntary wheel running, selection-line mice ran an average 2.7 times more revolutions per day compared with mice from nonselected control lines (26). Daily wheel-running distances among selection-line females averaged 16.2 km at generation 24 (21). Females of both selection and control lines run enough to train (physically condition) themselves, as demonstrated by the increased activity of mitochondrial (e.g., citrate synthase, cytochrome-c oxidase, pyruvate dehydrogenase) and glycolytic enzymes (e.g., hexokinase) (24), and increased hematocrit and blood hemoglobin concentration (unpublished data) after 8 wk of wheel access. Selection-line females also have reduced body mass (48) and reduced fat mass (45) compared with control lines, suggesting a possible trade-off between energy expenditures for growth and activity (5).
Because wheel running is both energetically expensive and potentially physiologically taxing, we expected that corticosterone played a role in supporting this type of voluntary exercise. We developed four specific hypotheses. First, as has been shown in many previous studies of mammals, we predicted that plasma corticosterone levels would rise acutely in proportion to the amount of wheel-running activity during some relatively short period of time before sampling. Second, because mice from selection lines exhibit much higher activity on running wheels (at night), we predicted that, compared with mice from control lines, they would show higher levels of corticosterone during activity. Third, we predicted that the acute response to wheel running would increase over time with chronic wheel access. Voluntary exercise is presumably less psychologically stressful than forced running, such that the corticosterone response we measured should predominately reflect exercise-induced changes. In voluntarily exercising female hamsters, the model most similar to our own, chronic exercise led to enhanced glucocorticoid synthesis and release (6). Fourth, we hypothesized that, in the absence of wheels, corticosterone levels in mice from selection lines would not differ from those in control-line mice. These hypotheses were tested in selection and control lines of female mice housed either with or without wheel access for 8 wk beginning at 26 days of age.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Study animals. Juvenile female Hsd:ICR mice (Mus domesticus) were used for the experiment, which was approved by the Institutional Animal Care and Use Committee (IACUC). Females were chosen as the study sex because they demonstrate greater levels of voluntary wheel running than males and have higher peak corticosterone levels in response to exercise (12). Female mice were taken from generation 21 (second litters) of an artificial selection experiment for high voluntary wheel running (46). At generation 21, first-litter females from the four replicate selection lines were running an average of 14,300 revolutions/day on days 5 and 6 of a 6-day test, whereas females from the four randomly bred control lines averaged 5,100 revolutions/day. Pups for this study were weaned at 21 days of age, at which time two females from each of six families per line (n = 96 mice) were chosen at random. Each female was weighed, toe clipped for identification, and housed individually. At 25-27 days of age, the first blood sample (day 0) was collected (see Blood sampling for corticosterone). Immediately after blood sampling, one sister of each pair (no-wheel group) was individually housed in a standard shoebox cage (27 × 17 × 12.5 cm), and the other (wheel-access group) was individually housed in a similar cage but with continuous access to a large running wheel (1.12 m circumference) through a short tube. Animals were maintained on a 12:12-h light-dark cycle with ad libitum access to food (Harlan Teklad Rodent Diet W8604) and water and were weighed weekly. Activity in the wheels was automatically recorded in 1-min bins by computer. Wheel-running data were summarized as total revolutions per day, total number of active 1-min intervals (bins in which any revolutions were recorded) per day, and mean speed (total revolutions divided by number of active intervals). Stage of estrous cycle was determined by vaginal smears within 2 h after blood sampling, beginning at 5 wk of age, following the five stages outlined by Rugh (40). Treatment continued for 52 days.
Blood sampling for corticosterone. Blood samples for corticosterone determination were collected at six times over 52 days with 7-14 days between sampling. Blood was collected 1-3 h after lights on (days 0, 15, 43) and 1-3 h after lights off (nights 8, 29, 50). Small volume (<50 µl) blood samples were drawn by retro-orbital puncture without anesthesia in <2.0 min from first disturbing the mouse. Blood sampling was performed by an experienced researcher (I. Girard) under a protocol approved by the IACUC. Mice were monitored by the staff veterinarian, and none of the 96 females suffered any detectable injuries as a result of the six blood collections.
Blood was collected in heparinized microhematocrit tubes, centrifuged, and the separated plasma was stored at
80°C until analysis.
Steroids were extracted and corticosterone was purified as in a
previous experiment (12) (for a complete methodology, see
Ref. 1). In brief, steroids were extracted from plasma with 7.5 ml ether in two washes. The corticosterone fraction was eluted with 50% ethyl acetate in isooctane from a celite microcolumn with a 1:1 ethylene glycol-to-propylene glycol solid phase.
Corticosterone concentrations (ng/ml plasma) were determined for
duplicate aliquots by radioimmunoassay. Specific binding in the
corticosterone assays was 48.1 ± 4.9% (SD, n = 11) and the limit of detection was 2 ng/ml; intra-assay
coefficient of variation was <5.5%; interassay coefficient of
variation was 11.1% for the low-corticosterone standard and 9.2% for
the high-corticosterone standard. A maximum of 50 samples (in
duplicate) could be included in one assay run. As our primary interest
was a comparison between selection and control animals within a
treatment, samples within a treatment group were analyzed together in a
single run to reduce interassay variation.
Statistical analyses. Statistical analyses were performed by using PROC MIXED in SAS (6.0). For all analyses, the effect of selection history was included as a fixed main effect, and replicate lines were nested within selection history as random effects. The effects of selection history and wheel access on body mass each week was tested with a two-way mixed-model ANOVA. The effect of selection history on wheel running was tested with a mixed-model analysis of covarience (ANCOVA) including wheel freeness as a covariate.
Statistical analyses of corticosterone were conducted separately for each treatment group, except for day 0 before treatment began. Statistical comparisons between treatments were not made, as our hypotheses concerned the effects of selection history on corticosterone. The effect of selection history on corticosterone was tested for each treatment with a mixed-model ANCOVA, including time required to collect blood from first disturbance of the animal, time of day, (z-transform of time of day)2, arousal state (sleeping/resting or alert/active), wheel freeness, and stage of estrous cycle (where applicable) as covariates or cofactors. In wheel-access mice, the acute effect of wheel running on corticosterone was tested by using revolutions in the 20 min before sampling as a covariate in the above model, replacing arousal state. In preliminary analyses, wheel running in the previous 20 min was the best predictor of corticosterone (highest R2) among the measures of wheel activity tested (revolutions in the previous 5, 10, 20, 30, 60, and 120 min). The chronic effect of wheel running on the corticosterone response to exercise was examined in wheel-access mice by testing for both a main effect of treatment day (i.e., sample nights 8, 29, and 50) and a change in the acute effect of wheel running over time (interaction of wheel running and treatment day). The significance of the main effect of treatment and of the interaction (wheel running in previous 20 min × treatment day) was tested in a repeated-measures, mixed-model ANCOVA with covariates and cofactors as described above for the acute-effect model. The relationship between corticosterone and body mass increase over the rapid growth phase (days 0-29) was examined with a two-way mixed-model ANCOVA with selection history and treatment as main effects and body mass at day 29 as the dependent variable. The model included mass at day 0, mean night corticosterone (average of nights 8 and 29), and mean day corticosterone (average of days 0 and 15) as covariates, as well as the interactions between each of the two corticosterone variables and selection history. Further analyses on the effects of mass at day 0 and mean night corticosterone on mass at day 29 were conducted on each of the four treatment groups separately. Although the work of Borer (6) suggests that acute response of plasma corticosterone levels should increase with training (exposure to running wheels), we did not have clear predictions for changes in basal (daytime) levels or active (nighttime) levels in animals without wheel access. Therefore, for simplicity, we report two-tailed P values throughout.| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Wheel running.
On average, mice from selection lines ran more revolutions per day than
those from control lines during each of the 52 treatment days (Fig.
1A). Wheel running generally
increased over the first 3 wk of wheel access, then stabilized over
weeks 4-8. Over days 14-52, mice from selection lines ran an average of
14,474 ± 741 (SE) revolutions/day, and mice from control lines
ran an average of 6,456 ± 426 revolutions/ day [effect of
selection history: F(1, 6) = 23.3, P = 0.003]. Most of the difference in number of wheel revolutions between
selection and control lines was caused by the greater average running
speed [F(1, 6) = 31.3, P = 0.002] of
the selection lines (30.3 ± 1.21 revolutions per active 1-min interval) compared with the control lines (14.1 ± 0.67 revolutions/min), with no statistically significant difference in the
average time spent running per day over days
14-52 [selection lines: 474 ± 14.5 min/day;
control lines: 423 ± 21.9 min/day; F(1, 6) = 0.84, P = 0.30].
|
Plasma corticosterone levels in day and night samples.
The effects of selection history, arousal state, and stage of estrous
cycle on plasma corticosterone levels are summarized in Table
1. No differences in morning plasma
corticosterone levels existed between female mice from selection and
control lines just before initiation of treatment at 26 ± 1 days
of age. In wheel-access mice, females from selection lines had
significantly higher plasma corticosterone levels at night
8, day 15, and night 29. In mice housed
without wheels, selection-line females had significantly higher plasma
corticosterone levels at day 15, night 29, and
night 50. Arousal state (resting/sleeping or alert/active)
was a highly significant predictor of corticosterone level in most
samplings of wheel-access mice (night 8, day 15,
night 29, and day 43) but was a significant
cofactor only for day 43 in no-wheel mice. The number of
alert/active animals at the first morning sampling was 4 selection and
10 control mice (wheel-treatment groups combined, total
n = 96). In wheel-access mice, the number of
alert/active animals was as follows: night 8 (17 selection,
19 control); day 15 (8 selection, 11 control); night
29 (24 selection, 21 control); day 43 (8 selection, 13 control); night 50 (24 selection, 23 control). In no-wheel
mice, the number of alert/active animals was as follows: night
8 (11 selection, 9 control); day 15 (5 selection, 11 control); night 29 (17 selection, 15 control); day
43 (14 selection, 10 control); night 50 (22 selection,
20 control).
|
Acute and chronic effects of wheel running on corticosterone. Although differences in the overall plasma corticosterone levels were found (see above), once plasma corticosterone levels were adjusted statistically for the amount of wheel running 20-min immediately before sampling, no selection-history differences remained [F(1, 6) < 4.2, P > 0.08; Table 3].
At night, females from selection lines tended to run more revolutions in the 20 min before blood sampling than did control-line mice, but the difference was significant only at night 29 (Table 2). On day 15, control-line females ran significantly more than selection-line females in the 20 min before sampling, although the amount of wheel running was relatively low compared with night sampling periods. The number of revolutions in the 20 min before blood sampling was a significant positive predictor of plasma corticosterone levels at day 15 and in all night samples (Table 3). The acute effect of wheel running was not different between control and selection animals in any sampling period [interaction of wheel-running × selection history: F(1, 6) < 2.0, P > 0.3], as illustrated in Fig. 2. The partial regression coefficients (b' ± SE) for the effect of wheel running on (square-root transformed) plasma corticosterone were 0.015 ± 0.006 (night 8), 0.012 ± 0.003 (night 29), and 0.019 ± 0.006 (night 50).
|
|
|
Body mass.
Body mass was not significantly different between control and selection
lines either at weaning [n = 96, F(1,
6) < 0.5, P > 0.8] or just before initiation of
treatment [F(1, 6) < 0.5, P > 0.7;
Fig. 3]. Mass increased over the first 3 wk of treatment in all animals and was significantly higher in control
females than in selection females in week 4 [day
22: F(1, 6) = 6.91, P = 0.039],
week 5 [day 29: F(1, 6) = 6.14, P = 0.048], week 7 [day 43:
F(1, 6) = 6.13, P = 0.047], and
week 8 [day 50: F(1, 6) = 7.03, P = 0.038]. The main effect of wheel access was
significant only at day 50 [F(1, 6) = 10.2, P = 0.019], when animals housed without wheels had
higher mass than wheel-access mice. No significant interaction between
selection history and treatment existed in any week.
|
Relationships among wheel running, plasma corticosterone, and growth. Over the first 4 wk of treatment (days 0 through 29), selection females increased mass by an average of 6.83 ± 0.32 g (treatment groups combined), compared with an increase of 9.24 ± 0.32 g in control mice. Body-mass increase over the first 4 wk was inversely related to the average night corticosterone values in each of the four groups. In an analysis of all animals, mass at day 29 of treatment was predicted by mass at day 0 [partial F(1, 63) = 23.2, P < 0.0001, positive slope] and by mean night corticosterone [F(1, 63) = 12.7, P < 0.0001, negative slope] but not by mean day corticosterone [F(1, 63) = 1.87, P = 0.18, negative slope]. In this analysis, selection history [partial F(1, 6) = 5.57, P = 0.06], treatment [F(1, 63) = 1.42, P < 0.24], and the interactions of selection history and treatment with corticosterone [F(1, 6) < 2.15, P > 0.15] were not significant predictors of mass at day 29.
When each group was examined separately, mean night corticosterone was a negative and statistically significant predictor of mass at day 29 in each, as illustrated in Fig. 4, A and B [significance of the effect of mean night corticosterone in wheel-access selection: partial F(1, 14) = 4.85, P = 0.045; wheel-access control: F(1, 17) = 7.94, P = 0.012; no-wheel selection: F(1, 16) = 12.8, P = 0.003; no-wheel control: F(1, 13) = 10.6, P = 0.006]. (Note: exclusion of the selection animal with a mean corticosterone value of 593 ng/ml did not change the results.) Interestingly, initial mass (day 0) was a significant positive predictor (F > 10.6, P < 0.007) of mass at day 29 in three groups but was not a significant predictor in the analysis of wheel-access control animals [F(1, 17) = 1.57, P = 0.23, but slope was still positive].
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Our results demonstrate that the acute response of plasma corticosterone is directly and linearly related to the amount of voluntary exercise in house mice, confirming the general findings of a proportional plasma corticosterone response under conditions of moderate or heavy exercise. As demonstrated in earlier studies of chronic wheel access in these mice (21, 27, 48), females voluntarily exercised for several hours each night at levels that appeared to be of moderate to heavy intensity. Mean wheel-running speeds during peak activity over weeks 3-8 were 32 (control) and 85% (selection) of the estimated maximal aerobic speed (3.4 km/h for a 23-g mouse; from Fig. 6 of Ref. 28). As expected, selection animals had higher absolute corticosterone levels than controls during two nocturnal sampling periods (nights 29 and 50), but this difference was explainable by the greater wheel running of selection mice in the minutes before sampling.
No evidence of a training effect on corticosterone response to exercise was found after chronic wheel access, as the acute response of corticosterone to the amount of wheel running in the previous 20 min was consistent across 50 days of wheel access and never differed between control and selection groups. These results appear to be among the first reports of corticosterone response to chronic high voluntary exercise in a nonhuman animal (see Ref. 6 for changes in basal steroidogenesis in voluntarily exercising hamsters) and may provide the clearest evidence that, in some animals, the acute corticosterone response is unaffected by chronic, moderate to heavy voluntary exercise.
Although no selection-history effect was found among wheel-access animals, selection females housed in regular cages without wheels had significantly higher corticosterone levels than controls without wheels in one daytime and two nighttime sampling periods. Because we have no measure of locomotor activity in groups housed without wheels, we cannot determine whether corticosterone is related to home-cage activity. In a separate study of home-cage activity at generation 24, selection females housed in photobeam activity-cages had 3.7-fold greater ambulations than control mice on the second day of a 2-day test in cages larger than those used in the present study (38). These data suggest that the differences in corticosterone levels among animals in home cages might also be explained in part by differences in locomotor activity in the absence of wheels. However, we do not know if such differences would persist for several weeks. Moreover, results from previous studies suggest that home-cage activity is physiologically less taxing than wheel running, which does elicit responses consistent with endurance-training effects. Compared with "sedentary" animals, wheel-access mice demonstrated increases in maximum aerobic capacity (47) and in metabolic capacities of the hindlimb (24) and endurance of the gastrocnemius (57). It is unlikely that selection mice without wheels were exercising at the same intensity as their counterparts with wheel access, even though the treatment groups demonstrated plasma corticosterone levels of similar magnitude. Therefore, home-cage activity may be a poor predictor of corticosterone levels in animals without wheels, a hypothesis that could be tested with the use of photobeam activity cages.
Alternatively, the high corticosterone levels of selection females housed without wheels may be reflective of a modulation of the HPA axis as a result of selection for increased wheel-running behavior. Upregulation of the HPA axis could result in both increased wheel-running behavior and increased corticosterone release downstream. One potential mediator of such a relationship is corticotropin-releasing factor (CRF). CRF stimulates corticotropin and glucocorticoid secretion but also has behavioral effects in the central nervous system (31, 36), independent of its action on the anterior pituitary. Central administration of CRF can produce dramatic increases in locomotor activity in both rats (25, 44) and mice (19), depending on dose and testing conditions. This effect may be independent of CRF stimulation of the pituitary (19), as locomotor activation was not blocked by dexamethasone at a dose that prevented a CRF-induced rise in plasma corticosterone (8, 9), nor by hypophysectomy (20). Also, corticosterone itself may also play a role in promoting locomotor behavior.
Another explanation for the unexpectedly high corticosterone levels in the selection animals housed without wheels can be proposed but is difficult to test. It is possible that, for animals selectively bred for high wheel-running activity, the absence of a wheel is psychologically stressful. However, selection females with locked wheels unable to rotate actually demonstrated lower frequencies of biting and sniffing behaviors compared with controls (27). The behavior of mice unable to run on wheels is therefore not characterized by the increase in stereotypes normally observed in rodents under stress (55).
An unexpected finding was the consistent negative correlation between growth and endogenous corticosterone levels measured on nights 8 and 29 in each of the four treatment groups. We have previously reported that selection-line females demonstrated reduced body mass (generation 14; Ref. 48) and reduced fat mass (generation 13, whole body fat mass; Ref. 49; generation 17, retroperitoneal fat pad weight; Ref. 18) compared with control-line females. In the present study, lower early growth rates in selection females led to a significant difference in mass by the third week of treatment compared with controls, and this difference was maintained into adulthood. Although a number of hypothetical relationships between wheel running, corticosterone, and growth can be suggested, our data, which are descriptive in nature, do not allow us to distinguish among them. One possibility is that reduction in growth rate and elevated plasma corticosterone are each correlated to responses of selection for high wheel running but are not causally related to each other. Arguing against this possibility is the fact that the negative relationship between growth and corticosterone levels was significant within each of the four groups, including the control animals not under selection for wheel running.
Instead, we suggest that wheel running, corticosterone levels during
activity, and suppression of growth may be linked at the level of the
central nervous system. As proposed above, one potential mediator of
such a relationship is CRF, which affects energy balance and release of
growth hormone. CRF is thought to play an important role in the control
of food intake and energy expenditure independently of its actions on
the HPA axis. Centrally administered CRF decreased food intake and body
mass in rats (4) and decreased food intake in fat-tailed
dunnarts (Sminthopsis crassicaudata; Ref. 23)
and goldfish (Carassius auratus; Ref. 15).
Hypersecretion of CRF may also be responsible for weight loss in
anorexia nervosa (25). Additionally, stress also inhibits secretion of growth hormone in rats (36), perhaps through
the action of CRF neurons. Central administration of CRF in rats
decreased growth hormone secretion in a dose-dependent manner
(35), and stress-induced decreases in plasma growth
hormone concentrations are blocked by pretreatment with the CRF
antagonist 
-helical CRF9-41 (39).
It is also possible that voluntary wheel running (and maybe voluntary home-cage activity) is causally related to both elevated corticosterone and reduced growth through separate pathways. Clearly the HPA axis responds acutely to exercise and causes elevated plasma corticosterone levels. Suppression of growth in exercising animals could result from limited energy availablility or through alterations in hormone pathways other than the HPA axis. Energy deficits from insufficient food or forced exercise can result in reduced body mass (5). In rats, daily voluntary running reduced fat, protein, and body mass in young males (but not females), possibly through the involvement of gonadal hormones (13). Obviously, level of running and selection history are confounded in our study, and we are prevented from any substantive discussion of the relationships of wheel running, corticosterone, and growth. Experimental studies, perhaps with adrenalectomized animals or with manipulation of CRH levels, will be required to elucidate this interesting finding.
| |
ACKNOWLEDGEMENTS |
|---|
We thank Michael Stern and Kevin E. Bonine for help with collection of blood samples; Drs. David H. Abbott and Wendy Saltzman of the Wisconsin Regional Primate Research Center for contributions to the experimental design; Dan Wittwer of Assay Services for essential training and valuable laboratory assistance; Jeff Alexander and Wayne Nehls for excellent animal maintenance; Drs. Lisa Krugner-Higby and Janet Welter for attentive care of our animals; Justin S. Rhodes for assistance with statistical analyses; and J. S. R. and W. S. for helpful comments on various versions of the manuscript.
| |
FOOTNOTES |
|---|
The study was funded by U.S. National Science Foundation Grant IBN-9728434 (to T. Garland, Jr.).
Present address of T. Garland, Jr.: Department of Biology, University of California, Riverside, CA 92521.
Address for reprint requests and other correspondence: I. Girard, Dept. of Zoology, 430 Lincoln Drive, Univ. of Wisconsin-Madison, Madison, WI 53706 (E-mail: igirard{at}facstaff.wisc.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
10.1152/japplphysiol.00465.2001
Received 10 May 2001; accepted in final form 23 November 2001.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Abraham, GE,
Buster JE,
Lucas LA,
Corrales PC,
and
Teller RC.
Chromatographic separation of steroid hormones for use in radioimmunoassay.
Anal Lett
5:
509-511,
1972.
2.
Astheimer, LB,
Buttemer WA,
and
Wingfield JC.
Interactions of corticosterone with feeding, activity, and metabolism in passerine birds.
Ornis Scand
23:
355-365,
1992.
3.
Belthoff, JR,
and
Dufty AM, Jr.
Corticosterone, body condition and locomotor activity: a model for dispersal in screech-owls.
Anim Behav
55:
405-415,
1998.
4.
Benoit, SC,
Thiele TE,
Heinrichs SC,
Rushing PA,
Blake KA,
and
Steeley RJ.
Comparison of central administration of corticotropin-releasing hormone and urocortin on food intake, conditioned taste aversion, and c-Fos expression.
Peptides
21:
345-351,
2000.
5.
Borer, KT.
Neurohumoral mediation of exercise-induced growth.
Med Sci Sports Exerc
26:
741-754,
1994.
6.
Borer, KT,
Bestervelt LL,
Mannheim M,
Brosamer MB,
Thompson M,
Swamy U,
and
Piper WN.
Stimulation by voluntary exercise of adrenal glucocorticoid secretion in mature female hamsters.
Physiol Behav
51:
713-718,
1992.
7.
Breuner, CW,
Greenberg AL,
and
Wingfield JC.
Noninvasive cortisocterone treatment rapidly increases activity in Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii).
Gen Comp Endocrinol
111:
386-394,
1998.
8.
Britton, DR,
Varela M,
Garcia A,
and
Rosenthal M.
Dexamethasone suppresses pituitary-adrenal but not behavioral effects of centrally administered CRF.
Life Sci
38:
211-216,
1986.
9.
Britton, KT,
Lee G,
Dana R,
Risch SC,
and
Koob GF.
Activating and "anxiogenic" effects of corticotropin releasing factor are not inhibited by blockade of the pituitary-adrenal system with dexamethasone.
Life Sci
39:
1281-1286,
1986.
10.
Cash, WB,
and
Holberton RL.
Effects of exogenous corticosterone on locomotor activity in the red-eared slider turtle, Trachemys scripta elegans.
J Exp Zool
284:
637-644,
1999.
11.
Challet, E,
Le Maho Y,
Robin JP,
Malan A,
and
Cherel Y.
Involvement of corticosterone in the fasting-induced rise in protein utilization and locomotor activity.
Pharmacol Biochem Behav
50:
405-412,
1995.
12.
Coleman, MA,
Garland T, Jr,
Marler CA,
Newton SS,
Swallow JG,
and
Carter PA.
Glucocorticoid response to forced exercise in laboratory house mice (Mus domesticus).
Physiol Behav
63:
279-285,
1998.
13.
Cortright, RN,
Chandler MP,
Lemon PWR,
and
DiCarlo SE.
Daily exercise reduces fat, protein and body mass in male but not female rats.
Physiol Behav
62:
105-111,
1997.
14.
Dellwo, M,
and
Beauchene RE.
The effect of exercise, diet restriction, and aging on the pituitary: adrenal axis in the rat.
Exp Gerontol
25:
553-562,
1990.
15.
De Pedro, N,
Alonso-Gomez AL,
Gancedo B,
Valenciano AI,
Delgado MJ,
and
Alonso-Bedate M.
Effect of alpha-helical-CRF[9-41] on feeding in goldfish: involvement of cortisol and catecholamines.
Behav Neurosci
111:
398-403,
1997.
16.
Deschenes, MR,
Kraemer WJ,
Maresh CM,
and
Crivello JF.
Exercise-induced hormonal changes and their effects upon skeletal muscle tissue.
Sports Med
12:
80-93,
1991.
17.
Devenport, L,
Doughty D,
Heiberger B,
Burton D,
Brown R,
and
Stith R.
Exercise endurance in rats: roles of type I and II corticosteroid receptors.
Physiol Behav
53:
1171-1175,
1993.
18.
Dumke, CL,
Rhodes JS,
Garland T, Jr,
Maslowski E,
Swallow JG,
Wetter AC,
and
Cartee GD.
Genetic selection of mice for high voluntary wheel running: effect on skeletal muscle glucose uptake.
J Appl Physiol
91:
1289-1297,
2001.
19.
Dunn, AJ,
and
Berridge CW.
Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses?
Brain Res Rev
15:
71-100,
1990.
20.
Eaves, M,
Thatcher-Britton K,
Rivier J,
Vale W,
and
Koob GF.
Effects of corticotropin releasing factor on locomotor activity in hypophysectomized rats.
Peptides
6:
923-926,
1985.
21.
Girard, I,
McAleer MW,
Rhodes JS,
and
Garland T, Jr.
Selection for high voluntary wheel running increases speed and intermittency in house mice (Mus domesticus).
J Exp Biol
204:
4311-4320,
2001.
22.
Hennessy, MB.
Sensitization of the plasma corticosterone response to novel environments.
Physiol Behav
50:
1175-1180,
1991.
23.
Hope, PJ,
Turnbull H,
Farr S,
Morley JE,
Rice KC,
Chrousos GP,
Torpy DJ,
and
Wittert GA.
Peripheral administration of CRF and urocortin: effects on food intake and the HPA axis in the marsupial Sminthopsis crassicaudata.
Peptides
21:
669-677,
2000.
24.
Houle-Leroy, P,
Garland T, Jr,
Swallow JG,
and
Guderley H.
Effects of voluntary activity and genetic selection on muscle metabolic capacities in house mice Mus domesticus.
J Appl Physiol
89:
1608-1616,
2000.
25.
Koob, GF,
and
Britton KT.
Behavioral effects of corticotropin-releasing factor.
In: Corticotropin-Releasing Factor: Basic and Clinical Studies of a Neuropeptide, edited by De Souza EB,
and Nemeroff CB.. Boca Raton, FL: CRC, 1990, p. 253-266.
26.
Koteja, P,
and
Garland T, Jr.
Response to R. Eikelboom.
Anim Behav
61:
F25-F26,
2001.
27.
Koteja, P,
Garland T, Jr,
Sax JK,
Swallow JG,
and
Carter PA.
Behaviour of house mice artificially selected for high levels of voluntary wheel running.
Anim Behav
58:
1307-1318,
1999.
28.
Koteja, P,
Swallow JG,
Carter PA,
and
Garland T, Jr.
Energy cost of wheel running in house mice: implications for coadaptation of locomotion and energy budgets.
Physiol Biochem Zool
72:
238-249,
1999.
29.
Kraemer, WJ,
Deschenes MR,
and
Fleck SJ.
Physiological adaptations to resistance exercise. Implications for athletic conditioning.
Sports Med
6:
246-256,
1988.
30.
Kraemer, WJ,
Fleck SJ,
Dziados JE,
Harman EA,
Marchitelli LJ,
Gordon SE,
Mello R,
Frykman PN,
Koziris LP,
and
Triplett NT.
Changes in hormonal concentrations after different heavy-resistance exercise protocols in women.
J Appl Physiol
75:
594-604,
1993.
31.
Krahn, DD,
Gosnell BA,
Levine AS,
and
Morley JE.
Behavioral effects of corticotropin-releasing factor: localization and characterization of central effects.
Brain Res
443:
63-69,
1988.
32.
Kuoppasalmi, K,
Naveri H,
Harkonen M,
and
Adlercreutz H.
Plasma cortisol, androstenedione, testosterone and luteinizing hormone in running exercise of different intensities.
Scand J Clin Lab Invest
40:
403-409,
1980.
33.
Lin, W,
Singer G,
and
Papasava M.
The role of adrenal corticosterone in schedule-induced wheel running.
Pharmacol Biochem Behav
30:
101-106,
1988.
34.
Neufeld, JH,
Breen L,
and
Hauger R.
Extreme posture elevates corticosterone in a forced ambulation model of chronic stress in rats.
Pharmacol Biochem Behav
47:
233-240,
1994.
35.
Ono, N,
Lumpkin MD,
Samson WK,
McDonald JK,
and
McCann SM.
Intrahypothalamic action of corticotrophin-releasing factor (CRF) to inhibit growth hormone and LH release in the rat.
Life Sci
35:
1117-1123,
1984.
36.
Owens, MJ,
and
Nemeroff CB.
Physiology and pharmcology of corticotropin-releasing factor.
Pharmacol Rev
43:
425-473,
1991.
37.
Piazza, PV,
Deroche V,
Deminiere JM,
Maccari S,
Le Moal M,
and
Simon H.
Corticosterone in the range of stress-induced levels possesses reinforcing properties: implications for sensation-seeking behaviors.
Proc Natl Acad Sci USA
90:
11738-11742,
1993.
38.
Rhodes, JS,
Hosack GR,
Girard I,
Kelley AE,
Mitchell GS,
and
Garland T, Jr.
Differential sensitivity to acute administration of cocaine, GBR 12909, and fluoxetine in mice selectively bred for hyperactive wheel-running behavior.
Psychopharmacology (Berl)
158:
120-131,
2001.
39.
Rivier, C,
and
Vale W.
Involvement of corticotropin-releasing factor and somatostatin in stress-induced inhibition of growth hormone secretion in the rat.
Endocrinology
117:
2478-2482,
1985.
40.
Rugh, R.
The Mouse: Its Reproduction and Development. Minneapolis, MN: Burgess, 1968.
41.
Schnabel, A,
Kindermann W,
Steinkraus V,
Salas-Fraire O,
and
Biro G.
Metabolic and hormonal responses to exhaustive supramaximal running with and without 
-adrenergic blockade.
Eur J Appl Physiol
52:
214-218,
1984.
42.
Shanks, N,
Griffiths J,
Zalcman S,
Zacharko RM,
and
Anisman H.
Mouse strain differences in plasma corticosterone following uncontrollable footshock.
Pharmacol Biochem Behav
36:
515-519,
1990.
43.
Snegovskaya, V,
and
Viru A.
Steroid and pituitary hormone responses to rowing: relative significance of exercise intensity and duration and performance level.
Eur J Appl Physiol
67:
59-65,
1993.
44.
Sutton, RE,
Koob GF,
Le Moal M,
Rivier J,
and
Vale W.
Corticotropin releasing factor produces behavioural activation in rats.
Nature
297:
331-333,
1982.
45.
Swallow, JG.
Artificial Selection for High Voluntary Activity in House Mice: a Study in Evolutionary Physiology (PhD thesis). Madison, WI: University of Wisconsin-Madison, 1998.
46.
Swallow, JG,
Carter PA,
and
Garland T, Jr.
Artificial selection for increased wheel-running behavior in house mice.
Behav Genet
28:
227-237,
1998.
47.
Swallow, JG,
Garland T, Jr,
Carter PA,
Zhan WZ,
and
Sieck GC.
Effects of voluntary activity and genetic selection on aerobic capacity in house mice (Mus domesticus).
J Appl Physiol
84:
69-76,
1998.
48.
Swallow, JG,
Koteja P,
Carter PA,
and
Garland T.
Artificial selection for increased wheel-running activity in house mice results in decreased body mass at maturity.
J Exp Biol
202:
2513-2520,
1999.
49.
Swallow, JG,
Koteja P,
Carter PA,
and
Garland TJ.
Food consumption and body composition in mice selected for high wheel-running activity.
J Comp Physiol B Biochem Syst Environ Physiol
204:
1177-1190,
2001.
50.
Sylvester, PW,
Forczek S,
Ip MM,
and
Ip C.
Exercise training and the differential prolactin response in male and female rats.
J Appl Physiol
67:
804-810,
1989.
51.
Tharp, GD.
The role of glucocorticoids in exercise.
Med Sci Sports Exerc
7:
6-11,
1975.
52.
Tharp, GD,
and
Buuck RJ.
Adrenal adaptation to chronic exercise.
J Appl Physiol
37:
720-722,
1974.
53.
Viru, M,
Litvinova L,
Smirnova T,
and
Viru A.
Glucocorticoids in metabolic control during exercise: glycogen metabolism.
J Sports Med Phys Fitness
34:
377-382,
1994.
54.
Von Holst, D.
The concept of stress and its relevance for animal behavior.
In: Stress and Behavior, edited by Mooler AP,
Milinski M,
and Slater PJB. San Diego, CA: Academic, 1998, p. 1-131.
55.
Wolfensohn, S,
and
Lloyd M.
Recognition of pain and stress in laboratory animals.
In: Handbook of Laboratory Animal Management and Welfare. Oxford, UK: Oxford University Press, 1994, p. 174-180.
56.
Wolkowitz, OM.
Prospective controlled studies of the behavioral and biological effects of exogenous corticosteroids.
Psychoneuroendocrinology
1994:
233-255,
1994.
57.
Zhan, WZ,
Swallow JG,
Garland T, Jr,
Proctor DN,
Carter PA,
and
Sieck GC.
Effects of genetic selection and voluntary activity on the medial gastrocnemius muscle in house mice.
J Appl Physiol
87:
2326-2333,
1999.
This article has been cited by other articles:
|
|
 |
|
  L. M. Vaanholt, B. De Jong, T. Garland Jr, S. Daan, and G. H. Visser Behavioural and physiological responses to increased foraging effort in male mice J. Exp. Biol., June 1, 2007; 210(11): 2013 - 2024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Colbert, V. Mai, J. A. Tooze, S. N. Perkins, D. Berrigan, and S. D. Hursting Negative energy balance induced by voluntary wheel running inhibits polyp development in APCMin mice Carcinogenesis, October 1, 2006; 27(10): 2103 - 2107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Marqueti, N. A. Parizotto, R. S. Chriguer, S. E. A. Perez, and H. S. Selistre-de-Araujo Androgenic-Anabolic Steroids Associated With Mechanical Loading Inhibit Matrix Metallopeptidase Activity and Affect the Remodeling of the Achilles Tendon in Rats Am. J. Sports Med., August 1, 2006; 34(8): 1274 - 1280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Garland Jr and S. A. Kelly Phenotypic plasticity and experimental evolution J. Exp. Biol., June 15, 2006; 209(12): 2344 - 2361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fediuc, J. E. Campbell, and M. C. Riddell Effect of voluntary wheel running on circadian corticosterone release and on HPA axis responsiveness to restraint stress in Sprague-Dawley rats J Appl Physiol, June 1, 2006; 100(6): 1867 - 1875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Park, O. Chan, Q. Li, M. Kiraly, S. G. Matthews, M. Vranic, and M. C. Riddell Changes in basal hypothalamo-pituitary-adrenal activity during exercise training are centrally mediated Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2005; 289(5): R1360 - R1371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Rezende, M. A. Chappell, F. R. Gomes, J. L. Malisch, and T. Garland Jr Maximal metabolic rates during voluntary exercise, forced exercise, and cold exposure in house mice selectively bred for high wheel-running J. Exp. Biol., June 15, 2005; 208(12): 2447 - 2458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Swallow, J. S. Rhodes, and T. Garland Jr. Phenotypic and Evolutionary Plasticity of Organ Masses in Response to Voluntary Exercise in House Mice Integr. Comp. Biol., June 1, 2005; 45(3): 426 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Rhodes, S. C. Gammie, and T. Garland Jr. Neurobiology of Mice Selected for High Voluntary Wheel-running Activity Integr. Comp. Biol., June 1, 2005; 45(3): 438 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Belter, H. V. Carey, and T. Garland Jr. Effects of voluntary exercise and genetic selection for high activity levels on HSP72 expression in house mice J Appl Physiol, April 1, 2004; 96(4): 1270 - 1276. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||
) and control (
) females
over 24 h during week 4 of treatment, 3 days before
blood sampling. Values are means ± SE.
) wheel access, and in
control female mice with (
) wheel access over 8 wk of treatment beginning at
26 ± 1 days of age. Values are means ± SE. * Significant
effect of selection history [F(1, 6) > 6.1, P < 0.05]. ** Significant effects of both
selection history and treatment [F(1, 6) = 10.2, P < 0.02] in a two-way nested ANCOVA.
