Circadian Rhythms In Rats Research Articles

Rat circadian rhythms entrain to a descending saw-tooth light intensity cycle

We reexamined whether rat circadian rhythms entrained to the light intensity cycle of a descending saw-tooth (ST-d) form, in which illuminance decreased rectilinearly from 300 lx to 0 lx in 24 h, and abruptly returned to 300 lx (lights-on time). Ambulation, drinking and subcutaneous body temperature were simultaneously monitored in 5 intact, 5 pinealectomized and 5 orchiectomized rats. Additionally, sleep was monitored in the intact rats. In all the rats, entrainment was confirmed during 65 days' exposure to the ST-d cycle. The waveforms of the entrained rhythms were much modified compared with those during LD 12:12. The estimated activity periods of the entrained rhythms straddled the lights-on time of the ST-d cycle. In all the groups of rats, administration of a single ST-d cycle in constant dim red light produced only delay shifts irrespective of its circadian phase, and there was no significant circadian variation in the magnitude of phase shifts. The results indicate that rat circadian rhythms entrain to the ST-d cycle with an unexpected phase position, which cannot be explained by the phase-response curve.

Hypothyroidism blunts light responsivity of rat circadian rhythms : Mark S. Bauer, M.D., Andrew Soloway, B.A., Mary Dratman, M.D., Margaret Kreider, Ph.D., Peter C. Whybrow, M.D. University of Pennsylvania, Philadelphia, PA 19104

Hypothyroidism blunts light responsivity of rat circadian rhythms : Mark S. Bauer, M.D., Andrew Soloway, B.A., Mary Dratman, M.D., Margaret Kreider, Ph.D., Peter C. Whybrow, M.D. University of Pennsylvania, Philadelphia, PA 19104

Effects of aging on food-entrained circadian rhythms in the rat

Twenty-four hour schedules of restricted food availability entrain a component of the circadian activity rhythm in rats via a food-entrainable pacemaker separate from the light-entrainable pacemaker. The effect of aging on food-entrained circadian rhythms was examined in 6 rats maintained on a restricted diurnal feeding schedule from age 3–21 months and again from 24–25 months. Food-entrainment, measured as behavioral anticipation of a 1-hr daily mealtime during the middle of the light period and persistence of this anticipation rhythm during food deprivation, was apparent in the aged rats when recorded in wheel-running cages from 20–21 months of age. Despite the long duration of restricted diurnal food access, the aged rats, like young rats, rapidly reverted to nocturnal activity when transferred to ad lib feeding. When restricted diurnal feeding was reinstated at 24 months age, these rats, now recorded in food-bin monitoring cages, required more time for a food anticipation pattern to emerge and showed a lower amplitude food anticipation rhythm compared to a group of young adult rats. These age-related changes are similar to those that characterize photically entrained circadian rhythms and suggest that both components of the rat's multioscillatory circadian timekeeping system deteriorate in parallel over the life span.

Sex differences in the development of the motor activity circadian rhythm in rats under constant light

Differences between sexes in the maturation of the motor activity rhythm have been studied in rats (10 females and 7 males) born and raised under LL and isolated from the day of weaning. Motor activity data were registered every 30 minutes for 45 days after weaning. Periodogram analysis was applied to each animal data and the daily power spectra were calculated on the basis of the period, tau. The process of rhythm evolution was studied by means of an analysis of variance of a multivariant linear model, and by defining two mathematical functions that fit to the evolution of the total daily motor activity (TDMA) and the power content of the circadian harmonic (PCCH) through time: a sigmoidal function, which presents an inflexion point was used for the study of the evolution of the PCCH values through time; and a gaussian function, which presents a minimum was used for the evolution of the TDMA values. Results indicate that males show more ultradian components than females just after weaning, and take a longer time to acquire the circadian harmonic as the main harmonic in the daily power spectrum. The acquisition of the circadian character is preceeded by a decrease in the TDMA, in the case of the males and is followed by a decrease in TDMA in the case of the females. These results suggest sexual differences in the organization and maturation of the circadian system in rats.

Characteristics of Food-Entrained Orcadian Rhythms in Rats During Long-Term Exposure to Constant Light

Rats possess a system of circadian oscillators that permit entrainment of circadian activity rhythms independently to 24 hr cycles of light-dark and food access. The nature of interactions between food- and light-entrainable oscillators was examined by observing the generation and persistence of food-entrained circadian rhythms in rats whose light-entrainable rhythms were eliminated by long-term exposure to constant light. Most of these rats showed a delayed generation of food-entrained rhythms and only one of eight animals showed persistence of food associated rhythms during a 4-day food deprivation test. Rats whose light-entrainable rhythms are eliminated by suprachiasmatic nuclei ablation show, in contrast, normal generation and persistence of food-entrained rhythms. The results suggested a disruptive influence of constant light on non-photic entrainment, possibly due to coupling forces between damped light-entrainable oscillators and the food-entrainable oscillators.

Effect of ovariectomy and estradiol on unity of female rat circadian rhythms

Sixteen rats were ovariectomized and given either a 1-cm implant of crystalline estradiol-17 beta (eight rats) or an empty implant (eight rats). A further six rats were sham ovariectomized and given empty implants, and eight rats were left unoperated. The rats were exposed to 70 days of constant dim light (LL) with a maximum illumination level of 20 lx, and circadian running and drinking rhythms were monitored. In LL, both the running and drinking activity rhythms of the ovariectomized, blank-implanted rats became markedly disrupted, whereas unoperated and sham-operated rats maintained unified rhythms. Estradiol-implanted rats developed fewer rhythm desynchronies, and the majority displayed a single band of free-running activity. Rather than being arrhythmic, the activity of the LL-exposed ovariectomized rats appeared to contain several free-running components. Thus these data are consistent with the concept of a multioscillatory basis to the circadian system and support a role for the ovary and its hormone estradiol in the maintenance of coherence between component oscillators.

Melatonin and circadian control in mammals.

Although pinealectomy has little influence on the circadian locomotor rhythms of laboratory rats, administration of the pineal hormone melatonin has profound effects. Evidence for this comes from studies in which pharmacological doses of melatonin are administered under conditions of external desynchronization, internal desynchronization, steady state light-dark conditions, and phase shifts of the zeitgeber. Taken together with recent findings on melatonin receptor concentration in the rat hypothalamus, particularly at the level of the suprachiasmatic nuclei, these results suggest that melatonin is a potent synchronizer of rat circadian rhythms and has a direct action on the circadian pacemaker. It is possible, therefore, that the natural role of endogenous melatonin is to act as an internal zeitgeber for the total circadian structure of mammals at the level of cell, tissue, organ, whole organism and interaction of that organism with environmental photoperiod changes.

Food-Anticipatory Circadian Rhythms in Rats with Paraventricular and Lateral Hypothalamic Ablations

Neural mechanisms generating food-anticipatory circadian rhythms in rats are sep arate from the suprachiasmatic nuclei, a putative circadian pacemaker for light-entrainable circadian rhythms. We attempted to localize these mechanisms using lesions focused on the paraventricular and lateral hypothalamic areas, two regions that have functional properties likely to characterize a food-entrainable circadian oscillator. Rats with complete radiofre quency ablation of the paraventricular and suprachiasmatic nuclei or ibotenic acid destruction of the lateral hypothalamus showed anticipatory circadian rhythms to a 2-hr daily mealtime, as measured by locomotor activity or activity directed toward a food bin. The long-term continued function of the meal-associated oscillator was also unaffected by the lesions, as demonstrated by a reappearance of activity at the former mealtime during 3 days of starvation after 11 or 12 days of ad libitum feeding. Several rats with total or partial paraventricular lesions failed to exhibit anticipatory locomotor activity, but did show anticipatory food- bin-related activity. These hypothalamic lesions may alter the probability of particular antic ipatory behaviors, but they do not eliminate the food-entrainable circadian timekeeping func tion.

Alterations of motor activity circadian rhythm in rats with adjuvant arthritis

Adjuvant arthritis in rats produces alterations in the motor activity circadian rhythm. Specifically arthritic animals show a decrease in the total daily motor activity and an advance in the acrophase of the rhythm. Slight changes are also observed in the power content of the circadian harmonic as well as in the amplitude.

Reentrainment of rat circadian activity rhythms: effects of melatonin.

Experiments were conducted to determine whether daily melatonin injections could influence reentrainment of circadian locomotor activity rhythms in male Long-Evans rats after phase shifts of the light dark (LD) cycle. When exposed to a 5-h advance of the LD cycle, six out of 15 rats injected daily with melatonin at the new dark onset reentrained by a phase delay of the activity rhythm. The remaining nine melatonin-injected rats and 14 of the 15 control injected rats phase advanced. Daily melatonin injections administered at the old dark onset did not alter direction of reentraining transients but decreased latency to reach steady-state entrainment. In contrast, the effects of melatonin injections given at the end of both the old and new dark periods are difficult to interpret due to the effects of the injection procedure itself at these times. Following an 8-h advance of the LD cycle, all melatonin-injected rats phase advanced while all vehicle and uninjected control rats phase delayed when injections were given at the old dark onset. As has been found in other research areas, the time of day of melatonin administration appears to be a critical factor in its mode of action. It is yet to be established whether these results from the use of pharmacological doses of melatonin are indicative of endogenous melatonin's involvement in the circadian reentrainment mechanism.

Development of circadian rhythms in rats with lesions of serotonergic system

In order to assess the role of the serotonergic system in the development of overt circadian rhythms in the rat, serotonin neurons in the brain were destroyed either by thermocoagulation of the median raphe (MRL) or by an intracerebroventricular injection of the neurotoxin, 5,7-dihydroxytryptamine (DHT). The reductions in serotonin content induced by two manipulations with MRL and DHT were 41% and 100% in the striatum, 40% and 66% in the hypothalamus, and 62% and 88% in the hippocampus, respectively. Neither manipulation eliminated the expression of circadian rhythms in corticosterone (CS) secretion, locomotor activity and drinking behavior, and changed the phase relationship in the overt CS rhythm. Also, 5,7-DHT treatments did not significantly affect the free-running period in locomotor activity. However, the emergence of CS circadian rhythm was delayed for one week in both MRL and DHT groups compared to the intact control ones. These results suggested that a serotonergic system would not be essential for the generation of the endogenous rhythm and the photoentrainment of overt circadian rhythms, but seems to participate in the only development of CS rhythms during the early stage of life.

Characteristics of SCN independent circadian rhythms in rats given methamphetamine

Characteristics of SCN independent circadian rhythms in rats given methamphetamine

Dose-dependent entrainment of rat circadian rhythms by daily injection of melatonin.

Previous work in our laboratory has shown that daily injection of large doses of the pineal hormone melatonin entrains the free-running locomotor rhythms of rats held in constant darkness and synchronizes the disrupted patterns of rats maintained in constant bright light. The present experiments determined the dose-response characteristics of entrainment to daily melatonin injections and made preliminary biochemical estimates of blood melatonin levels and half-lives after two critical doses of the hormone. The data indicated that the median effective dose for melatonin as an entraining agent in free-running rats was 5.45 +/- 1.33 micrograms/kg, considerably lower than doses previously employed and lower than doses employed in reproductive and metabolic studies in rats and hamsters. The data further indicated that the response to melatonin was quantal; rats either entrained to melatonin or they did not. No "partial entrainment" was evident, nor were there differences in phase angle, activity, or period among all effective doses. Biochemical estimates of blood melatonin after either 1 mg/kg or 1 microgram/kg of melatonin indicated that all effective doses resulted in supraphysiological levels of blood melatonin, although doses of 1 microgram/kg resulted in blood levels that were within one order of magnitude of normal nighttime values. Together, the data suggest that the rat circadian system is sensitive to the pineal hormone melatonin at or below doses required to effect rodent reproduction. Whether this sensitivity reflects a role for the pineal gland in rat circadian organization, however, still remains to be determined.

The ACTH-(4–9) analog ORG 2766 and desglycinamide 9-(Arg 8)-vasopressin reverse the retrograde amnesia induced by disrupting circadian rhythms in rats

Disrupting circadian organization by exposing rats to a shifted illumination schedule after training for passive avoidance and shuttle box avoidance behavior resulted in retrograde amnesia as evidenced by impaired performance during retention and extinction testing respectively. A single treatment with either the ACTH-(4–9) analog ORG 2766 or desglycinamide 9-(Arg 8)-vasopressin (DGAVP) 1 hour prior to the retention of passive avoidance or extinction of shuttle box avoidance behavior restored the behavioral impairment. It is suggested that these peptides may be useful to relieve memory deficits induced by disturbances in circadian organization.

Effects of methamphetamine on development of circadian rhythms in rats

To determine the effect of continuous methamphetamine treatment on development of the circadian system, the daily courses of spontaneous locomotor activity and plasma corticosterone level were determined in infant rats. Methamphetamine was dissolved in drinking water at a concentration of 0.005%, and administered to rats from postnatal day 14. The circadian locomotor rhythm in methamphetamine treated rats was not significantly different from that in non-treated rats for the first 4 weeks of drug treatment. Then the rhythm began to show signs of relative coordination and finally split into two activity components. One component entrained to the light-dark cycle, whereas the other free-ran in spite of the light cycle. The rhythm of plasma corticosterone in the methamphetamine treated group was not different from that in the control group at 4 weeks after birth, but was significantly phase-delayed at 8 weeks. Splitting was not observed for the corticosterone rhythm. It is concluded that continuous administration of methamphetamine to infant rats affects the circadian rhythms for spontaneous locomotor activity and plasma corticosterone level. Possible mechanisms of methamphetamine effects were discussed in terms of the circadian system underlying these rhythms.

Acute effect of methyl bromide on sleep-wakefulness and its circadian rhythms in rats.

Acute effect of methyl bromide on sleep-wakefulness and its circadian rhythms in rats.

Effects of continuous supply of light or carbachol to the SCN on the rat free-running rhythm.

Exposure to continuous light (LL) results in elongation of the free-running period of the rat circadian rhythm. However, the LL may not always mean constant intensity of light for the suprachiasmatic nucleus (SCN), since rats may regulate contrast of illumination by their eyelids which are closed during sleep phase. The removal of eyelids caused shortening of the free-running period or arrhythmicity under LL. In addition, implantation of carbachol--acetylcholine agonist--near the SCN also resulted in similar effects.

Effect of constant light on the circadian rhythm in locomotor activity in intact or eyelids-removed rats.

According to the Aschoff's role, exposure to continuous light (LL) results in the elongation of the free-running period of the rat circadian rhythm. However, the LL may not always mean the constant intensity of the light for the suprachiasmatic nucleus, since the rat may regulate the contrast of the illumination by their eyelids which are closed during the sleep phase. In this study, the surgical removal of the eyelids under the LL caused arrhythmicity of the locomotor activity in 7 of 10 rats. The remaining 3 rats maintained the free-running rhythm after the removal of the eyelids. These results suggest that constant light may affect the free-running rhythm of the rat with or without eyelids in the different manner.

Entrainment of rat circadian rhythms by daily injection of melatonin depends upon the hypothalamic suprachiasmatic nuclei

Although pinealectomy has little effect on the generation of circadian rhythmicity by mammals, daily injections of the pineal hormone melatonin entrain free-running rats [30]. The present study was designed to determine if known components of mammalian circadian organization were necessary for melatonin entrainment. Rats received either lesions to the suprachiasmatic nuclei (SCN), sham-lesions or neurotoxic lesions to brain catecholamines or serotonin. They were then allowed to free-run in constant dim red light (DD) before each received daily injections of either 1 mg/kg melatonin or ethanol:saline vehicle for 90 days. They were allowed to free-run for 30 days afterwards. Rats which received sham-lesions or neurotoxic lesions entrained to melatonin injections but not to vehicle. Rats which received complete SCN lesions were unaffected by melatonin or vehicle. These data suggest that the behavioral effects of melatonin, like those on reproduction in seasonally breeding mammals, depend upon an intact circadian system and the SCN.

Lithium effects on selected circadian rhythms in rats

Treating rats with lithium results in clear phase-delays in certain circadian rhythms but has no effect upon other rhythms. Phase-delays can be seen in running-wheel activity rhythms but under certain conditions, phase changes are not noted in SCN 2-DG uptake or pineal melatonin rhythms.