Nonphotic Phase Shifting in the Old and the Cold

When confined to novel running wheels or when given injections of triazolam in their home cages, old hamsters do not become as active as young hamsters. Therefore, lack of nonphotic phase shifting following such manipulations may stem from insufficient activity or arousal. Phase advances can be obtained in some 10-month-old animals when wheel running during the pulse is increased by the presence of females in estrous condition and in most 18-month-old hamsters by combining confinement to a novel wheel with triazolam injections. These data suggest that there is relatively little if anything wrong in aging hamsters with the nonphotic phase-shifting mechanism itself. The reason why in certain situations old hamsters do not shift appears to be because the nonphotic inputs to these shifting mechanisms are not strong enough. However, when running in novel wheels is increased by carrying out the tests at cold temperatures, most old animals did not show subsequent phase shifts. Evidently it is not running per se that is critical for phase shifts, but probably the motivational context for such running.     

Neuropeptide Y microinjected into the suprachiasmatic region phase shifts circadian rhythms in constant darkness

The geniculohypothalamic tract (GHT) is a projection from the intergeniculate leaflet to the suprachiasmatic nucleus (SCN). The GHT exhibits neuropeptide Y (NPY) immunoreactivity and appears to communicate photic information to the SCN. Microinjection of NPY into the SCN has been found to phase shift circadian rhythms of hamsters housed in constant light in a manner similar to the phase shifts produced by pulses of darkness or triazolam injections. In the present study, NPY was injected into the SCN of Syrian hamsters housed in constant darkness and was found to produce phase shifts similar to those seen in hamsters housed in constant light. Microinjections were not followed by wheel running during the subjective day (the time when NPY microinjections are followed by significant phase advances). These data suggest that NPY produces phase shifts by some mechanism other than by inducing wheel running or by inhibiting the response of SCN neurons to light and supports a role for NPY in nonphotic shifting of the circadian clock.     

Nonphotic phase shifting in female Syrian hamsters: interactions with the estrous cycle

Nonphotic phase shifting of circadian rhythms was examined in female Syrian hamsters. Animals were stimulated at zeitgeber time 4.5 by either placing them in a novel running wheel or by transferring them to a clean home cage. Placement in a clean home cage was more effective than novel wheel treatment in stimulating large (> 1.5 h) phase shifts. Peak phase shifts (ca. 3.5 h) and the percentage of females showing large phase shifts were comparable to those found in male hamsters stimulated with novel wheels. The amount of activity induced by nonphotic stimulation and the amount of phase shifting varied slightly with respect to the 4-day estrous cycle. Animals tended to run less and shift less on the day of estrus. Nonphotic stimulation on proestrus often resulted in a 1-day delay of the estrous cycle reflected in animals' postovulatory vaginal discharge and the expression of sexual receptivity (lordosis). This delay of the estrous cycle was associated with large phase advances and high activity. These results extend the generality of nonphotic phase shifting to females for the first time and raise the possibility that resetting of circadian rhythms can induce changes in the estrous cycle.     

Phase shifting by novelty-induced running: activity dose-response curves at different circadian times

This study compared phase shifting after novelty-induced running at different circadian times (CTs). In Experiment 1, hamsters were confined to novel wheels for 3 h, starting at CTs 2, 4, 6, 8, 10 or 22. The largest shifts were found at CTs 2, 4 and 6. At each CT there was a relationship between the number of revolutions during the pulse and the size of phase shift. Maximum shifts were usually observed at each CT when animals ran 5000–9000 revolutions during the pulse. In Experiment 2, hamsters were confined to novel wheels for 1 h, also starting at CTs 2, 4, 6, 8, 10 or 22. Unlike with 3-h pulses, the largest shifts with 1-h pulses occurred at CT 8. In Experiment 3, hamsters were shut into a small nest box after a 1-h pulse at CT 8; phase shifting was unaffected, showing that movement about the home cage after a 1-h pulse had ended was not required for shifting. At CTs 2, 4 and 22, 3-h pulses produced shifts but 1-h pulses did not. Possibly, there are two different mechanisms of nonphotic phase shifting that can be activated by being placed in a novel wheel, but the results can also be explained in terms of a single mechanism. Accepted: 8 August 1997     

Effects of food deprivation on locomotor activity, plasma glucose, and circadian clock resetting in Syrian hamsters

Circadian rhythms in Syrian hamsters can be phase advanced by activity or arousal stimulated during the daily rest phase ("subjective day"). A widely used method for stimulating activity is confinement to a novel wheel. Some hamsters decline to run, and some procedures may reduce the probability of running. The authors evaluated food deprivation (FD) as a method to promote running. Given evidence that perturbations of cell metabolism or glucose availability may affect circadian clock function in some tissues or species, they also assessed the effects of FD on free-running circadian phase, resetting responses to photic and nonphotic stimuli and plasma glucose. In constant light, a 27-h fast significantly increased running in a novel wheel and marginally increased the average size of resulting phase shifts. FD, without novel wheel confinement, was associated with some very large phase shifts or disruption of rhythmicity in hamsters that spontaneously ran in their home wheels during the subjective day. Hamsters that ran only during the usual active phase (subjective night) or that were prevented from running did not exhibit phase shifts, despite refeeding in the mid-subjective day. Using an Aschoff Type II design for measuring shifts, a 27-h fast significantly increased the number of hamsters that ran continuously when confined to a novel wheel but did not affect the dose-response relation between the amount of running and the size of the resulting shift. A day of fasting also did not affect the size of phase delay or advance shifts to 30-min light pulses in the subjective night. Plasma glucose was markedly reduced by wheel running in combination with fasting but was increased by running in nonfasted hamsters. These results establish FD as a useful tool for stimulating activity in home cage or novel wheels and indicate that in Syrian hamsters, significant alterations in glucose availability, associated with running, fasting, and refeeding, have surprisingly little effect on circadian pacemaker function.     

τ Changes After Single Nonphotic Events

Changes in the free-running period of the circadian rhythms of hamsters occur after single nonphotic events such as a 3-h pulse of running induced by being put in a novel wheel. These changes are mostly in the direction of longer periods, and can exceed 0.2 h; the magnitude of the effect depends on the circadian phase of the pulse. The phase response curves for period changes do not match up with those for phase shifts of the rhythms. Data on free-running rhythms after anisomycin injections and after novelty-induced wheel running in τ mutant hamsters support the view that period changes and phase shifts can occur independently of one another.     

Circadian clock resetting by sleep deprivation without exercise in Syrian hamsters: dark pulses revisited

Circadian rhythms in Syrian hamsters can be phase shifted by procedures that stimulate wheel running ("exercise") in the mid-subjective day (the hamster's usual sleep period). The authors recently demonstrated that keeping hamsters awake by gentle handling, without continuous running, is sufficient to mimic this effect. Here, the authors assessed whether wakefulness, independent of wheel running, also mediates phase shifts to dark pulses during the midsubjective day in hamsters free-running in constant light (LL). With running wheels locked during a 3 h dark pulse on day 3 of LL, hamsters (N = 16) averaged only 43+/-15 min of spontaneous wake time and phase shifted only 24+/-43 min. When wheels were open during a dark pulse, two hamsters remained awake, ran continuously, and showed phase advance shifts of 7.3 h and 8.7 h, respectively, whereas the other hamsters were awake <60 min and shifted only 45+/-38 min. No animals stayed awake for 3 h without running. Additional time in LL (10 and 20 days) did not potentiate the waking or phase shift response to dark pulses. When all hamsters were sleep deprived with wheels locked during a dark pulse, phase advance shifts averaged 261+/-110 min and ranged up to 7.3 h. These shifts are large compared to those previously observed in response to the 3 h sleep deprivation procedure. Additional tests revealed that this potentiated shift response is dependent on LL prior to sleep deprivation but not LL after sleep deprivation. A final sleep deprivation test showed that a small part of the potentiation may be due to suppression of spontaneous wheel running by LL. These results indicate that some correlate of waking, other than continuous running, mediates the phase-shifting effect of dark pulses in the mid-subjective day. The mechanism by which LL potentiates shifting remains to be determined. The lack of effect of subsequent LL on the magnitude of shifts to sleep deprivation in the dark suggests that LL reduces responsivity to light by processes that take >3 h of dark to reverse.     

Triazolam and Phase-Shifting Acceleration Re-Evaluated

In two experiments, triazolam (2.5 and 1.5 mg/animal) failed to significantly enhance the rate of re-entrainment of hamsters (Mesocricetus auratus) to an 8-hr advance of their light-dark cycle. Evidently the phase-shifting effects of triazolam are not robust. The animals did not run much in their wheels in response to the drug in these two experiments. In a third experiment, triazolam (0.5 and 2.5 mg/animal) produced phase advances of activity rhythms of hamsters in the dark. In this experiment, running in response to the drug was greater. Hamsters given triazolam but confined to their nest boxes over the next few hours did not show phase shifts. The phase-shifting effects of triazolam (when they do occur) appear to be mediated through activity increases. Triazolam-treated hamsters became ataxic in all three of these experiments. Suggestions that triazolam may be useful in ameliorating rhythm disturbances in people should be treated with a caution.     

Double-pulse experiments with nonphotic and photic phase-shifting stimuli.

Three-hour pulses of novelty-induced wheel running in the early to middle subjective day of golden hamsters produced phase advances of 2-3 hr. This phase shifting could be almost totally abolished by a light pulse following within 3 hr of the exercise pulse. When light pulses occurred about 8 hr after the exercise pulses, the phase-advancing effects of the latter were enhanced. Consideration of the amplitude of the phase response curve (PRC) for light pulses alone, in the test paradigms used here, showed that nonphotic and photic phase shifts did not combine additively. Antagonistic and synergistic interactions between photic and nonphotic shifts may have to be taken into account if it transpires that exercise in people can be used to assist adjustment to new schedules after crossing time zones, or in shiftwork.     

Nonphotic phase shifting in hamster clock mutants.

Golden hamsters with the tau mutation were kept in the dark and induced to become active through confinement to a novel running wheel for 3 hr. The response of the mutants to this nonphotic phase-shifting stimulus differed from that of wild-type hamsters. The mutants showed larger phase shifts, and their phase response curves differed in shape, with an advance portion at about circadian time 24, a phase at which wild types show delays. The results establish that the tau mutation, in addition to its already known effects, alters the response of the circadian system to nonphotic events.     

Feeding melatonin enhances the phase shifting response to triazolam in both young and old golden hamsters

Aging alters many aspects of circadian rhythmicity, including responsivity to phase-shifting stimuli and the amplitude of the rhythm of melatonin secretion. As melatonin is both an output from and an input to the circadian clock, we hypothesized that the decreased melatonin levels exhibited by old hamsters may adversely impact the circadian system as a whole. We enhanced the diurnal rhythm of melatonin by feeding melatonin to young and old hamsters. Animals of both age groups on the melatonin diet showed larger phase shifts than control-fed animals in response to an injection with the benzodiazepine triazolam at a circadian time known to induce phase advances in the activity rhythm of young animals. Thus melatonin treatment can increase the sensitivity of the circadian timing system of young animals to a nonphotic stimulus, and the ability to increase this sensitivity persists into old age, indicating exogenous melatonin might be useful in reversing at least some age-related changes in circadian clock function.     

Behavioral and Serotonergic Regulation of Circadian Rhythms

Endogenous depression is often accompanied by alterations in core parameters of circadian rhythms, and antidepressant treatments, including serotonergic drugs, sleep deprivation and exercise, alter circadian phase or period in humans or animal models. Antidepressants may act in part through the circadian system, and behavioral antidepressants through a common serotonergic path to the clock. This review evaluates the evidence from animal models that serotonin (5-HT) mediates phase-shifting effects of behavioral stimuli on circadian rhythms. In rodents, 'exercise' stimulated during the rest phase of the rest-activity cycle induces large phase shifts of circadian rhythms. These shifts can be mimicked by short-term sleep deprivation without intense activity. During wheel running or sleep deprivation, 5-HT release in the suprachiasmatic nucleus (SCN) circadian clock is significantly elevated. Lesions of 5-HT afferents to the SCN attenuate phase shifts or entrainment induced by activity in response to some stimuli (e.g., triazolam injections in hamsters, treadmill running in mice) but not others (e.g., novel wheel confinement in hamsters). Antagonists selective to 5HT_{1, 2} or ₇ receptors do not attenuate shifts induced by wheel running, although 5-HT_2/7 antagonists do partially block shifts to saline injections. 5-HT agonists (e.g., 8-OH-DPAT) induce large shifts in vitro, but much smaller shifts in vivo, particularly if administered directly to the SCN. Procedures for inducing 5-HT supersensitivity in vivo result in larger shifts to 8-OH-DPAT. 5-HT stimuli may affect the clock by direct and indirect pathways, particularly through the thalamic intergeniculate leaflet, and the role of these pathways may differ across species. At the level of the SCN, 5-HT likely acts through 5-HT₇ receptors on neurons and possibly also glial cells. These receptors may be useful targets for the development of antidepressant drugs. In aggregate, the literature provides mixed support for the hypothesis that exercise or behavioral arousal shift the circadian clock by a 5-HT pathway; the role of indirect pathways, interactions with other transmitters, cellular adaptations to denervation, glial cells, and species differences remain to be more fully clarified. Serotonergic and behavioral stimuli provide an intriguing route to elucidate the circadian clockworks and their possible role in depression.     

Changes in phase-angle under light–dark cycles influenced by nonphotic stimulation

ABSTRACT

Most work looking at nonphotic effects on circadian rhythms is conducted when animals are held under freerunning conditions, usually constant darkness. However, for nonphotic effects to be functionally significant, they should be demonstrable under conditions in which most animals live, i.e., a 24-hr light–dark cycle (LD). Syrian hamsters held in LD 6:18 were administered nonphotic stimulation in the form of a 3-hr confinement to a novel wheel starting about 6 hr before the start of their normal nightly activity bout. This resulted in a 2.5-hr advance of their activity rhythm on the next day that gradually receded to about 1.5 hr over the next 10 days. When hamsters held in LD 6:18 were given five novel wheel confinements over 13 days their nightly activity onset advanced 3 hr and remained at that phase for at least 2 weeks. Home cage wheel deprivation experiments indicated that high levels of home cage activity are necessary to maintain the advanced phase. These results show that nonphotic stimulation can have large, long-lasting effects on daily rhythms in LD and suggest a possible mechanism whereby nocturnal rodents might achieve phase flexibility in response to seasonal changes.     

Age-related changes in circadian responses to dark pulses

Aging involves many alterations in circadian rhythms, including a loss of sensitivity to both photic and nonphotic time signals. This study investigated the sensitivity of young and old hamsters to the phase advancing effect of a 6-h dark pulse on the locomotor activity rhythm. Each hamster was tested four times during a period of approximately 9 mo; periods of exposure to a 14-h photoperiod were alternated with the periods of exposure to constant light (20-80 lx), during which the dark pulses were administered. There was no significant difference in the phase shifts exhibited by the young (4-10 mo) and old hamsters (19-25 mo) or in the amount of wheel running activity displayed during each dark pulse. However, young hamsters had a significantly greater propensity to exhibit split rhythms immediately after the dark pulses. These results suggest that, although aging does not reduce the sensitivity of the circadian pacemaker to this nonphotic signal, it alters one property of the pacemaker, i.e., the flexibility of the coupling of its component oscillators.     

Intensive voluntary wheel running may restore circadian activity rhythms and improves the impaired cognitive performance of arrhythmic Djungarian hamsters

Circadian rhythms are highly important not only for the synchronization of animals and humans with their periodic environment but also for their fitness. Accordingly, the disruption of the circadian system may have adverse consequences. A certain number of animals in our breeding stock of Djungarian hamsters are episodically active throughout the day. Also body temperature and melatonin lack 24-h rhythms. Obviously in these animals, the suprachiasmatic nuclei (SCN) as the central pacemaker do not generate a circadian signal. Moreover, these so-called arrhythmic (AR) hamsters have cognitive deficits. Since motor activity is believed to stabilize circadian rhythms, we investigated the effect of voluntary wheel running. Hamsters were bred and kept under standardized housing conditions with food and water ad libitum and a 14 L/10 D lighting regimen. AR animals were selected according to their activity pattern obtained by means of passive infrared motion detectors. In a first step, the daily activity behavior was investigated for 3 weeks each without and with running wheels. To estimate putative photic masking effects, hamsters were exposed to light (LPs) and DPs and also released into constant darkness for a minimum of 3 weeks. A novel object recognition (NOR) test was performed to evaluate cognitive abilities both before and after 3 weeks of wheel availability. The activity patterns of hamsters with low wheel activity were still AR. With more intense running, daily patterns with higher values in the dark time were obtained. Obviously, this was due to masking as LPs did suppress and DPs induced motor activity. When transferred to constant darkness, in some animals the daily rhythm disappeared. In other hamsters, namely those which used the wheels most actively, the rhythm was preserved and free-ran, what can be taken as indication of a reconstitution of circadian rhythmicity. Also, animals showing a 24-h activity pattern after 3 weeks of extensive wheel running were able to recognize the novel object in the NOR test but not so before. The results show that voluntary exercise may reestablish circadian rhythmicity and improve cognitive performance.     

Behavioral and Serotonergic Regulation of Circadian Rhythms

Endogenous depression is often accompanied by alterations in core parameters of circadian rhythms, and antidepressant treatments, including serotonergic drugs, sleep deprivation and exercise, alter circadian phase or period in humans or animal models. Antidepressants may act in part through the circadian system, and behavioral antidepressants through a common serotonergic path to the clock. This review evaluates the evidence from animal models that serotonin (5-HT) mediates phase-shifting effects of behavioral stimuli on circadian rhythms. In rodents, 'exercise' stimulated during the rest phase of the rest-activity cycle induces large phase shifts of circadian rhythms. These shifts can be mimicked by short-term sleep deprivation without intense activity. During wheel running or sleep deprivation, 5-HT release in the suprachiasmatic nucleus (SCN) circadian clock is significantly elevated. Lesions of 5-HT afferents to the SCN attenuate phase shifts or entrainment induced by activity in response to some stimuli (e.g., triazolam injections in hamsters, treadmill running in mice) but not others (e.g., novel wheel confinement in hamsters). Antagonists selective to 5HT_{1, 2} or ₇ receptors do not attenuate shifts induced by wheel running, although 5-HT_2/7 antagonists do partially block shifts to saline injections. 5-HT agonists (e.g., 8-OH-DPAT) induce large shifts in vitro, but much smaller shifts in vivo, particularly if administered directly to the SCN. Procedures for inducing 5-HT supersensitivity in vivo result in larger shifts to 8-OH-DPAT. 5-HT stimuli may affect the clock by direct and indirect pathways, particularly through the thalamic intergeniculate leaflet, and the role of these pathways may differ across species. At the level of the SCN, 5-HT likely acts through 5-HT₇ receptors on neurons and possibly also glial cells. These receptors may be useful targets for the development of antidepressant drugs. In aggregate, the literature provides mixed support for the hypothesis that exercise or behavioral arousal shift the circadian clock by a 5-HT pathway; the role of indirect pathways, interactions with other transmitters, cellular adaptations to denervation, glial cells, and species differences remain to be more fully clarified. Serotonergic and behavioral stimuli provide an intriguing route to elucidate the circadian clockworks and their possible role in depression.     

Nonphotic entrainment in a diurnal mammal, the European ground squirrel (Spermophilus citellus).

Entrainment by nonphotic, activity-inducing stimuli has been investigated in detail in nocturnal rodents, but little is known about nonphotic entrainment in diurnal animals. Comparative studies would offer the opportunity to distinguish between two possibilities. (1) If nonphotic phase shifts depend on the phase of the activity cycle, the phase response curve (PRC) should be about 180 degrees out of phase in nocturnal and diurnal mammals. (2) If nonphotic phase shifts depend on the phase of the pacemaker, the two PRCs should be in phase. We used the diurnal European ground squirrel (Spermophilus citellus) in a nonphotic entrainment experiment to distinguish between the two possibilities. Ten European ground squirrels were kept under dim red light (<1 lux) and 20 +/- 1 degrees C. During the entrainment phase of the experiment, the animals were confined every 23.5 h (T) to a running wheel for 3 h. The circadian rhythms of 6 squirrels entrained, 2 continued to free run, and 2 possibly entrained but displayed arrhythmicity during the experiment. In a second experiment, a photic pulse was used in a similar protocol. Five out of 9 squirrels entrained, 1 did not entrain, and 3 yielded ambiguous results. During stable entrainment, the phase-advancing nonphotic pulses coincided with the end of the subjective day, while phase-advancing light pulses coincided with the start of the subjective day: mean psi(nonphotic) = 11.4 h; mean psi(photic) = 0.9 h (psi defined as the difference between the onset of activity and the start of the pulse). The data for nonphotic entrainment correspond well with those from similar experiments with nocturnal Syrian hamsters where psi(nonphotic) varied from 8.09 to 11.34 h. This indicates that the circadian phase response to a nonphotic activity-inducing stimulus depends on the phase of the pacemaker rather than on the phase of the activity cycle.     

Patterns of wheel running are related to Fos expression in neuropeptide-Y-containing neurons in the intergeniculate leaflet of Arvicanthis niloticus

A variety of nonphotic influences on circadian rhythms have been documented in mammals. In hamsters, one such influence, running in a novel wheel, is mediated in part by the pathway extending from neuropeptide-Y (NPY)-containing cells within the intergeniculate leaflet (IGL) of the thalamus to the hypothalamic suprachiasmatic nucleus (SCN). Arvicanthis niloticus is a species in which all individuals are diurnal with respect to general activity and body temperature when they are housed without a running wheel, but access to a running wheel induces a subset of individuals to become nocturnal. In the first study, the authors evaluated the possibility that nocturnal and diurnal patterns of wheel running in Arvicanthis are correlated with differences in IGL function. Adult male Arvicanthis housed in a 12:12 light-dark (LD) cycle were monitored in wheels, classified as nocturnal or diurnal, and then perfused either 4 h after lights-on or 4 h after lights-off. Sections through the intergeniculate leaflet were processed for immunohistochemical labeling of Fos and NPY. The percentage of NPY cells that expressed Fos was significantly influenced by an interaction between time of day and phenotype such that it rose from night to day in diurnal animals, and from day to night in nocturnal animals. In the second experiment, the authors established that running in a wheel actually induces Fos in the IGL of Arvicanthis. Specifically, the proportion of NPY cells expressing Fos was increased by access to wheels in nocturnal animals at night and in diurnal animals during the day. In the third experiment, the authors established that lesions of the IGL eliminate NPY fibers within the SCN, suggesting that these IGL cells project to the SCN in this species as has been established in other rodents. Together, these data demonstrate a clear difference in NPY cell function in nocturnal and diurnal Arvicanthis that appears to be caused, at least in part, by the differences in their wheel-running patterns, and that NPY cells within the IGL project to the SCN in Arvicanthis.     

Effects of wheel running on photoperiodic responses of Djungarian hamsters (Phodopus sungorus)

Djungarian hamsters (Phodopus sungorus) were exposed to artificial short days either with access to a running wheel (RW) or without. Within 6 weeks RW hamsters considerably increased their body mass, whereas controls showed the typical body mass reduction. Estimation of paired testis weights indicated a decelerated testis regression in RW hamsters. Subsequent locking of RWs for 9 weeks led to a decline in body mass of RW animals in parallel to controls. Daily torpor was almost completely missing in hamsters with initially unlocked wheels. During the final phase when RWs were again unlocked (3 weeks), body mass of exercising hamsters increased again, while controls reached the nadir in body mass. In comparison to equiponderate long-day (LD) controls the relative liver weight of RW hamsters was significantly increased unlike the relative heart weight. However, the latter tended to be higher than in sedentary LD hamsters. A growth-stimulating effect of wheel running was proven by elongated femora in exercising short-day (SD) hamsters compared to SD controls and suggested by exercise-induced elevation of body mass in a further experiment under continuous LD conditions, indicating a growth-promoting effect of wheel running independent from the photoperiod.     

Voluntary exercise stabilizes photic entrainment of djungarian hamsters (Phodopus sungorus) with a delayed activity onset

ABSTRACT

The Djungarian hamsters of our breeding colony show unstable daily activity patterns when kept under standard laboratory conditions. Moreover, part of them develops a delayed activity onset (DAO) or an arrhythmic phenotype. In former studies, we have shown that the system of photic entrainment works at its limits. If the period length (tau) increases, which is the case in DAO hamsters, the light-induced phase advances are too small to compensate the daily delay of the activity rhythm caused by tau being longer than 24 h. Accordingly, under natural conditions, there must be further (environmental) factors to enable a stable entrainment. One of these may be the higher level of motor activity. Animals must cover long distances to search for food, sexual partners and others. In the laboratory, hamsters are kept singly in small cages. This does restrict animals’ options for motor activity. Also, there is less need for moving around as the hamsters are fed ad libitum.

In the present study, a series of experiments was performed to investigate the putative effect of the activity level. To begin with, wild type (WT) and DAO animals were given access to running wheels. 50% of DAO hamsters developed a WT activity pattern. As the main reason for the DAO phenomenon is their long tau together with a too weak photic phase response, the effect of wheel running on these parameters was investigated in further experiments. With higher activity level, tau decreased in WT hamsters but increased in DAO animals even though the increase for the activity onset was only close to significance. Moreover, the photic phase responses were weaker though significant only for the activity offset of DAO hamsters.

Based on the assumptions that running wheel activity will affect the phase response and/or the free running period, the results of the present paper do not provide an explanation for why part of DAO hamsters developed a WT phenotype when they had access to running wheels. Obviously, mechanisms downstream from the suprachiasmatic nuclei must be taken into account when investigating the stabilizing, improving circadian entrainment effect of motor activity.