Prenatal stress alters circadian activity of hypothalamo-pituitary-adrenal axis and hippocampal corticosteroid receptors in adult rats of both gender.

Prenatal stress impairs activity of the hypothalamo-pituitary-adrenal (HPA) axis in response to stress in adult offspring. So far, very few data are available on the effects of prenatal stress on circadian functioning of the HPA axis. Here, we studied the effects of prenatal stress on the circadian rhythm of corticosterone secretion in male and female adult rats. To evaluate the effects of prenatal stress on various regulatory components of corticosterone secretion, we also assessed the diurnal fluctuation of adrenocorticotropin, total and free corticosterone levels, and hippocampal corticosteroid receptors. Finally, in the search of possible maternal factors, we studied the effects of repeated restraint stress on the pattern of corticosterone secretion in pregnant female rats. Results demonstrate that prenatal stress induced higher levels of total and free corticosterone secretion at the end of the light period in both males and females, and hypercorticism over the entire diurnal cycle in females. No diurnal fluctuation of adrenocorticotropin was observed in any group studied. The effects of prenatal stress on corticosterone secretion could be mediated, at least in part, by a reduction in corticosteroid receptors at specific times of day. Results also show that prepartal stress alters the pattern of corticosterone secretion in pregnant females. Those data indicate that prenatally stressed rats exhibit an altered temporal functioning of the HPA axis, which, taken together with their abnormal response to stress, reinforces the idea of a general homeostatic dysfunction in those animals.     

Prenatal stress alters circadian activity of hypothalamo–pituitary–adrenal axis and hippocampal corticosteroid receptors in adult rats of both gender

Prenatal stress impairs activity of the hypothalamo–pituitary–adrenal (HPA) axis in response to stress in adult offspring. So far, very few data are available on the effects of prenatal stress on circadian functioning of the HPA axis. Here, we studied the effects of prenatal stress on the circadian rhythm of corticosterone secretion in male and female adult rats. To evaluate the effects of prenatal stress on various regulatory components of corticosterone secretion, we also assessed the diurnal fluctuation of adrenocorticotropin, total and free corticosterone levels, and hippocampal corticosteroid receptors. Finally, in the search of possible maternal factors, we studied the effects of repeated restraint stress on the pattern of corticosterone secretion in pregnant female rats. Results demonstrate that prenatal stress induced higher levels of total and free corticosterone secretion at the end of the light period in both males and females, and hypercorticism over the entire diurnal cycle in females. No diurnal fluctuation of adrenocorticotropin was observed in any group studied. The effects of prenatal stress on corticosterone secretion could be mediated, at least in part, by a reduction in corticosteroid receptors at specific times of day. Results also show that prepartal stress alters the pattern of corticosterone secretion in pregnant females. Those data indicate that prenatally stressed rats exhibit an altered temporal functioning of the HPA axis, which, taken together with their abnormal response to stress, reinforces the idea of a general homeostatic dysfunction in those animals. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 302–315, 1999     

Circadian rhythm of circulating corticosterone and urinary excretion of catecholamines, serotonin and their catabolites in rats treated with imipramine

The circadian rhythm of serum corticosterone was assessed in rats entrained to a 12:12 LD cycle and treated with tricyclic imipramine (25 mg/kg/day) via osmotic pumps for a period of 14 days; urinary excretion of catecholamines, serotonin and their catabolites was also assessed. We observed that imipramine did not modify the phase position of the corticosterone rhythm but rather lowered the animal's responsiveness as shown by the lower peak of corticosterone at 2000 and by the smaller amplitude of its circadian rhythm; moreover imipramine had no effect on urinary excretion of catecholamines, serotonin and their catabolites during LD cycle.     

Restraint stress delays reentrainment in male and female diurnal and nocturnal rodents

A temporary loss of normal circadian entrainment, such as that associated with shift work and transmeridian travel, can result in an array of detrimental symptoms, making rapid reentrainment of rhythmicity essential. While there is a wealth of literature examining the effects of stress on the entrained circadian system, less is known about the influence of stress on circadian function following a phase shift of the light: dark (LD) cycle. The authors find that recovery of locomotor activity synchronization is altered by restraint stress in the diurnal rodent Octodon degus (degu) and the nocturnal rat. In the first experiment, degus were subjected to a 6-h phase advance of the LD cycle. Sixty minutes after the new lights-on, animals underwent 60 min of restraint stress. The number of days it took each animal to reentrain its activity rhythms to the new LD cycle was recorded and compared to the number of days it took the animal to reentrain under control conditions. When subjected to restraint stress, degus took 30% longer to reentrain their activity rhythms (p < 0.01). In a second experiment, rats underwent a similar experimental paradigm. As with the degus, stress significantly delayed the reentrainment of rats' activity rhythms (p < 0.01). There was no interaction between sex and stress on the rate of reentrainment for either rats or degus. Furthermore, there was no effect of stress on the free-running activity rhythm of degus, suggesting that the effect of stress on reentrainment rate is not secondary to alterations of period length. Together, these data point to a detrimental effect of stress on recovery of entrainment of circadian rhythms, which is independent of activity niche and sex.     

Effects of photoperiod on rat motor activity rhythm at the lower limit of entrainment

The experiment described here studied the rat motor activity pattern as a function of the photoperiod of circadian light-dark cycles in the limits of entrainment (22-and 23-h periods). In most cases, the overt rhythm showed 2 circadian components: 1 that followed the external LD cycle and a 2nd rhythm that was free run. The expression of these components was directly dependent on the photoperiod, and there was a gradual transition in the manifestation of 1 or the other. The component with a period equal to that of the external cycle was more manifested under long photoperiods, while the other 1 was more expressed during short photoperiods. Also, the period of the free-running component was longer under T22 than T23. For each period, the free-running component was longer under a longer photoperiod. At first sight, the presence of these 2 components in most of the rats might appear to be due to the fact that in the limits of entrainment, some rats do not entrain and thus show a free-running rhythm plus masking. However, the gradation observed in the different patterns of the overt motor activity rhythm, especially those patterns related to the different balance between the 2 components and the length of the period of the free-running component under LD as a function of the photoperiod, suggests that the circadian system can be functionally dissociated.     

Circadian locomotory rhythm and the influence of moulting in Australian field cricket nymphs

ABSTRACT. Evidence is presented for a circadian control of locomotory activity in the larval stadia of the cricket, Teleogryllus commodus Walker. Under light—dark cycles (LD), maximal activity occurs around the L/D transition and/or in the hours preceding it. Free-running rhythm patterns longer than 24 h are observed in constant light. Re-entrainment to phase advances in the LD cycle is also accompanied by several transient cycles. However, free-running rhythms under constant darkness or transients when exposed to LD cycle delays were not found. LD cycles during the eighth stadium set the phase of a free-running rhythm in the adult, even if the nymph does not show a rhythm. Nymphal activity is often erratic and is disrupted periodically by the moulting cycle, but moulting does not interrupt the operation of the circadian system. The daily timing of the moult itself is not under circadian control.     

Influence of the corticosterone rhythm on photic entrainment of locomotor activity in rats

The question of involvement of glucocorticoid hormones as temporal signals for the synchronization of the timekeeping system was addressed in rats with different corticosterone status. The authors showed that adrenalectomy had no effects on the synchronization of wheel-running activity rhythms to a steady-state LD 12:12 cycle, regardless of whether it was compensated for by a corticosterone replacement therapy that either reinstated constant plasma concentrations of the hormone or mimicked its natural rhythm. However, after a 12-h phase shift (daylight reversal), the lack of circulating corticosterone induced a significant shortening of the resynchronization rate (less than 3 days vs. 7 days). Normalization required restoration of a rhythmic corticosterone secretion that was synchronized to the new photoperiod. Under constant darkness, the corticosterone rhythm did not show any synchronizing effect, providing evidence that it participates in entrainment of the locomotor activity rhythm through modulation of light effects. It is proposed that, under stable lighting conditions, circulating glucocorticoids contribute to stabilizing activity rhythms by reinforcing resistance of the circadian timing system to variations of the photoperiod. Experimental evidence that serotonergic neurons are involved in relaying their modulatory effects to the clock is also presented.     

The Role of Wheel Running in the Coupling of Two Simultaneous Circadian Rhythms of Motor Activity in the Rat

Motor activity is among the non-photic stimuli that act on the internal clock. We have tested the role of motor activity in the circadian pattern of rats under conditions near the lower limits of entrainment, that induce circadian rhythm dissociation. Three groups of 8 rats each were used: a) rats kept individually in 25×25×15 cm cages, b) rats in 50×25×15 cm cages, and c) rats in 50×25×15 cm cages with access to a running wheel. All the rats were kept under light-dark cycles of 22 hours (T22, 11L:11D) for 50 days, after which they were transferred to constant darkness. All the rats without a running wheel showed a motor activity pattern with two statistically significant circadian rhythms in the periodogram of Sokolove and Bushell: one circadian component entrained by the LD cycle, and another free-running. The rats with access to a running wheel showed several patterns: 5 rats showed only one rhythm entrained to the LD cycle, 2 rats showed circadian rhythm dissociation, and 1 showed only a free running rhythm. We believe that the simultaneous manifestation of two circadian components reflects the functional dissociation of the oscillators population that constitutes the circadian pacemaker, of the rat. Physical exercise acts on the pacemaker reinforcing the strongest group of oscillators, which, depending on the structure of the circadian system of the rat, is usually the one entrained to the LD cycle. This study supports the hypothesis that motor activity couples the oscillators that form the circadian system of the rat.     

The Role of Wheel Running in the Coupling of Two Simultaneous Circadian Rhythms of Motor Activity in the Rat

Motor activity is among the non-photic stimuli that act on the internal clock. We have tested the role of motor activity in the circadian pattern of rats under conditions near the lower limits of entrainment, that induce circadian rhythm dissociation. Three groups of 8 rats each were used: a) rats kept individually in 25×25×15 cm cages, b) rats in 50×25×15 cm cages, and c) rats in 50×25×15 cm cages with access to a running wheel. All the rats were kept under light-dark cycles of 22 hours (T22, 11L:11D) for 50 days, after which they were transferred to constant darkness. All the rats without a running wheel showed a motor activity pattern with two statistically significant circadian rhythms in the periodogram of Sokolove and Bushell: one circadian component entrained by the LD cycle, and another free-running. The rats with access to a running wheel showed several patterns: 5 rats showed only one rhythm entrained to the LD cycle, 2 rats showed circadian rhythm dissociation, and 1 showed only a free running rhythm. We believe that the simultaneous manifestation of two circadian components reflects the functional dissociation of the oscillators population that constitutes the circadian pacemaker, of the rat. Physical exercise acts on the pacemaker reinforcing the strongest group of oscillators, which, depending on the structure of the circadian system of the rat, is usually the one entrained to the LD cycle. This study supports the hypothesis that motor activity couples the oscillators that form the circadian system of the rat.     

Evaluation of the inhibitory effect of circulating corticosteroids on circadian stimulated and stress induced secretion of ACTH in rats

Male rats were bilaterally adrenalectomized in order to measure the extent of inhibition exerted by endogenous corticosteroids on both basal ACTH secretion along its circadian rhythm and ether-stress induced ACTH secretion. In intact controls, plasma ACTH levels at the circadian maximum exceeded by 4 times the circadian minimum, and ACTH response 15 min after ether-stress surpassed the circadian minimum by 20 times. In adrenalectomized rats, the daily minimum was 8 times that of the controls. Nevertheless the circadian maximum was 3 times above the rhythm's minimum, while the maximal stress response (15 min) surpassed the circadian minimum by 8 times. In adrenalectomized rats supplemented with a solid source of corticosterone inducing a stable plasma corticosterone level equivalent to the controls' circadian minimum (3 micrograms/100 ml), the ACTH rhythm still fluctuated twice as high as in intact controls. The tonic feed-back inhibition exerted by endogenous corticosteroids on ACTH secretion appeared thus significantly stronger than the GABAergic inhibition to the corticotropic system which was previously studied under similar standard conditions.     

Characteristics of the circadian activity rhythm in common marmosets (Callithrix j. jacchus)

The circadian activity rhythm of the common marmoset, Callithrix j. jacchus was investigated by long-term recording of the locomotor activity of 15 individuals (5 males, 10 females) from 1.5 to 8 years old, both under constant illumination and under LD 12:12. The mean period of the spontaneous circadian rhythm was 23.2 ± 0.3 h. Neither sex-specific differences nor a systematic influence of light intensity on the spontaneous period were observed, but the period was dependent on the duration of the trial and on the age of the individual. Due to the short spontaneous period, in LD 12:12 there was a distinct advance of the activity phase with respect to the light time and a masking of the true onset of activity by the inhibitory direct effect of low light intensity during the dark time. After an 8 h delay shift of the LD 12:12, re-entrainment of the circadian activity rhythm required an average of 6.8 ± 0.7 days; the average re-entrainment time after an 8 h phase advance of the LD cycle was 8.6 ± 1.3 day. This directional effect is ascribed to characteristics of the phase-response curve. No ultradian components were observed, either in the LD-entrained or the free-running circadian activity rhythm.     

Circadian photoentrainment: parameters of phase delaying

Experiments were carried out using simulated den cages to delineate specific characteristics of phase delaying in circadian photoentrainment of a nocturnal rodent, the flying squirrel. The principal experiments entailed presentation of one to five consecutive 15-min white-light pulses per activity cycle at activity onset to animals free-running in darkness, in order to determine the immediate and final phase-shifting effect. Auxiliary experiments recorded entrainment patterns on light-dark (LD) schedules in the den cages. Phase response curves (PRCs) based on 15-min white-light pulses in standard wheel cages were also constructed for these animals as background information for interpreting the phase-delaying experiments. Exposure of a den animal to light by light sampling at the time of initial arousal from the rest state at circadian time (CT) 12, either by an LD schedule or by a 15-min light pulse, resulted in a return to the nest box for a short rest period. The phase delay occurring after a single light exposure at activity onset was equal to the induced rest, thus suggesting an immediate phase shift. The maximum delay was about 1 1/2 hr/cycle, with the amount of delay related to the number of light exposures. During the photoentrained state on an LD schedule, the activity rhythm of a den-housed animal was essentially free-running on the days following a phase delay. The data are used to expand current models for photoentrainment of circadian activity rhythms in nocturnal rodents.     

Plasma Corticosterone, Motor Activity and Metabolic Circadian Patterns in Streptozotocin-Induced Diabetic Rats

Experiments were conducted in male rats to study the effects of streptozotocin-induced diabetes on circadian rhythms of (a) plasma corticosterone concentrations; (b) motor activity; and (c) metabolic patterns. Animals were entrained to LD cycles of 12: 12 hr and fed ad libitum.

A daily rhythm of plasma corticosterone concentrations was found in controls animals with peak levels at 2400 hr and low values during the remaining hours. This rhythm was statistically confirmed by the cosinor method and had an amplitude of 3.37μg/100 ml and the acrophase at 100 hr. A loss of the normal circadian variation was observed in diabetic animals, with a nadir at the onset of light period and high values throughout the remaining hours; cosinor analysis of these data showed no circadian rhythm, delete and a higher mean level than controls.

As expected, normal rats presented most of their motor activity during the dark period with 80+ of total daily activity; the cosinor method demonstrated a circadian rhythm with an amplitude of 60+ of the mean level and the acrophase at 0852 hr. Both diabetic and control rats showed a similar activity during the light phase, but diabetic animals had less activity than controls during the night and their percentage of total daily activity was similar in both phases of the LD cycle (50+ for each one). With the cosinor method we were able to show the persistence of a circadian rhythm in the motor activity of diabetic rats, but with a mesor and amplitude lower than in controls (amplitude rested at 60+ of the mean level) and its acrophase advanced to 0148 hr.

The metabolic activity pattern of diabetic rats also changed: whereas controls showed a greater metabolic activity during the night (70+ food; 82+ water; 54+ urine; 67+ faeces), diabetics did not show differences between both phases of the LD cycle. Water ingested and urine excreted by the diabetic group were higher than normal during light and dark periods; food consumed and faeces excreted were higher than controls only in the light phase.

These data suggest that alterations in circadian rhythms of plasma corticosterone and motor activity are consecutive to the loss of the feeding circadian pattern, due to polyphagia and polydipsia showed by these animals, which need to extend intakes during the light and dark phases.     

Behavioral and neurochemical sources of variability of circadian period and phase: studies of circadian rhythms of npy-/- mice

The cycle length or period of the free-running rhythm is a key characteristic of circadian rhythms. In this study we verify prior reports that locomotor activity patterns and running wheel access can alter the circadian period, and we report that these treatments also increase variability of the circadian period between animals. We demonstrate that the loss of a neurochemical, neuropeptide Y (NPY), abolishes these influences and reduces the interindividual variability in clock period. These behavioral and environmental influences, from daily distribution of peak locomotor activity and from access to a running wheel, both act to push the mean circadian period to a value < 24 h. Magnitude of light-induced resetting is altered as well. When photoperiod was abruptly changed from a 18:6-h light-dark cycle (LD18:6) to LD6:18, mice deficient in NPY were slower to respond to the change in photoperiod by redistribution of their activity within the prolonged dark and eventually adopted a delayed phase angle of entrainment compared with controls. These results support the hypothesis that nonphotic influences on circadian period serve a useful function when animals must respond to abruptly changing photoperiods and point to the NPYergic pathway from the intergeniculate leaflet innervating the suprachiasmatic nucleus as a circuit mediating these effects.     

Locomotor activity rhythm in four wrasse species under varying light conditions

Under controlled laboratory conditions, the locomotor activity rhythms of four species of wrasses (Suezichthys gracilis, Thalassoma cupido, Labroides dimidiatus andCirrhilabrus temminckii) were individually examined using an actograph with infra-red photo-electric switches in a dark room at temperatures of 21.3–24.3°C, for 7 to 14 days. The locomotor activity ofS. gracilis occurred mostly during the light period under a light-dark cycle regimen (LD 12:12; 06:00-18:00 light, 18:00-06:00 dark). The locomotor activity commenced at the beginning of the light period and continued until a little before the beginning of dark period. The diel activity rhythm of this species synchronizes with LD. Under constant illumination (LL) this species shows distinct free-running activity rhythms varying in length from 23 hrs. 39 min. to 23 hrs. 47 min. Therefore,S. gracilis appears to have a circadian rhythm under LL. However, in constant darkness (DD), the activity of this species was greatly suppressed. All the fish showed no activity rhythms in DD conditions. After DD, the fish showed the diel activity rhythm with the resumption of LD, but this activity began shortly after the beginning of light period. The fish required several days to synchronize with the activity in the light period. Therefore,S. gracilis appeared to continue the circadian rhythm under DD. InT. cupido, the locomotor activity commenced somewhat earlier than the beginning of the light period and continued until the beginning of the dark period under LD. The diel activity rhythm of this species synchronizes with LD. Under LL, four of the five specimens of this species tested showed free-running activity rhythms for the first 5 days or longer varying in length from 22 hrs. 54 min. to 23 hrs. 39 min. Although the activity of this species was suppressed under DD, two of five fish showed free-running activity rhythms throughout the experimental period. The lengths of such free-running periods were from 23 hrs. 38 min. to 23 hrs. 50 min. under DD. Therefore, it was ascertained thatT. cupido has a circadian rhythm. InL. dimidiatus, the locomotor activity rhythm under LD resembled that observed inT. cupido. The diel activity rhythm of this species synchronizes with LD. Under LL, four of seven of this species showed free-running activity rhythms throughout the experimental period. The lengths of such free-running periods were from 23 hrs. 07 min. to 25 hrs. 48 min. Although the activity of this species was suppressed under DD, three of five fish showed free-running activity rhythms throughout the experimental period. The lengths of such free-running periods were from 23 hrs. 36 min. to 23 hrs. 41 min. under DD. Therefore, it was ascertained thatL. dimidiatus has a circadian rhythm. Almost all locomotor activity of C.temminckii occurred during the light period under LD. The diel activity rhythm of this species coincides with LD. Under LL, two of four of this species showed free-running activity rhythms throughout the experimental period. The lengths of such free-running periods were from 23 hrs. 32 min. to 23 hrs. 45 min. Although the activity of this species was suppressed under DD, one of the four fish showed free-running activity rhythms throughout the experimental period. The length of the free-running period was 23 hrs. 21 min. under DD. Therefore,C. temminckii appeared to have a circadian rhythm. According to field observations,S. gracilis burrows and lies in the sandy bottom whileT. cupido, L. dimidiatus, andC. temminckii hide and rest in spaces among piles of boulders or in crevices of rocks during the night. It seems that the differences in nocturnal behavior among the four species of wrasses mentioned above are closely related to the intensity of endogenous factors in their locomotor activity rhythms.     

Different light-dark cycles affect growth rate and food intake of mice

The adaptation of the endogenous rhythm of an organism to external cycles may influence the development of physiological processes in animals. Light not only synchronizes the circadian system, but also exerts profound direct effects: the immediate reduction of melatonin release at night-time and the inhibition of locomotor activity in nocturnal rodents after a light pulse are well-known examples, yet little is known about effects of different light/dark (LD) cycles on the level of corticosterone, growth hormone and growth rate. Mice were raised under different period length of LD cycle including LD5:5 (light: 5 h; dark: 5 h), LD12:12 (light: 12 h; dark: 12 h) and LD16:16 (light: 16 h; dark: 16 h) for four weeks. Mice in LD5:5 and LD16:16 groups manifested higher locomotor activity, plasma corticosterone and growth hormone concentrations and growth rate than the LD12:12 group. The results suggest that different LD cycles may affect many physiological processes including growth rate, food intake and hormones, and the change of growth rate in different LD cycles may be related to the level of corticosterone and growth hormone concentrations. The results also suggest that both the long-period LD cycle and short-period LD cycles can improve the growth of mice, but they disturbed the biorhythm stabilization and affected hormone secretion; in general, these conditions would not promote the animals' survival.     

Inhibiting cortisol response accelerates recovery from a photic phase shift

Jetlag results when a temporary loss of circadian entrainment alters phase relationships among internal rhythms and between an organism and the outside world. After a large shift in the light-dark (LD) cycle, rapid recovery of entrainment minimizes the negative effects of internal circadian disorganization. There is evidence in the existing literature for an activation of the hypothalamic-pituitary-adrenal (HPA) axis after a photic phase shift, and it is possible that the degree of HPA-axis response is a determining factor of reentrainment time. This study utilized a diurnal rodent, Octodon degus, to test the prediction that the alteration of cortisol levels would affect the reentrainment rate of circadian locomotor rhythms. In experiment 1, we examined the effects of decreased cortisol (using metyrapone, an 11beta-hydroxylase inhibitor) on the rate of running-wheel rhythm recovery after a 6-h photic phase advance. Metyrapone treatment significantly shortened the length of time it took animals to entrain to the new LD cycle (11.5% acceleration). In experiment 2, we examined the effects of increased cortisol on the rate of reentrainment after a 6-h photic phase advance. Increasing plasma cortisol levels increased the number of days (8%) animals took to reentrain running-wheel activity rhythms, but this effect did not reach significance. A third experiment replicated the results of experiment 1 and also demonstrated that suppression of HPA activity via dexamethasone injection is capable of accelerating reentrainment rates by approximately 33%. These studies provide support for an interaction between the stress axis and circadian rhythms in determining the rate of recovery from a phase shift of the LD cycle.     

Possible evidence for shift work schedules in the media workers of the ant species Camponotus compressus

The locomotor activity rhythm of the media workers of the ant species Camponotus compressus was monitored under constant conditions of the laboratory to understand the role of circadian clocks in social organization. The locomotor activity rhythm of most ants entrained to a 24 h light/dark (12:12 h; LD) cycle and free-ran under constant darkness (DD) with circadian periodicities. Under entrained conditions about 75% of media workers displayed nocturnal activity patterns, and the rest showed diurnal activity patterns. In free-running conditions these ants displayed three types of activity patterns (turn-around). The free-running period (τ) of the locomotor activity rhythm of some ants (10 out of 21) showed period lengthening, and those of a few (6 out of 21) showed period shortening, whereas the locomotor activity rhythm of the rest of the ants (5 out of 21) underwent large phase shifts. Interestingly, the pre-turn-around τ of those ants that showed nocturnal activity patterns during earlier LD entrainment was shorter than 24 h, which became greater than 24 h after 6-9 days of free-run in DD. On the other hand, the pre-turn-around τ of those ants, which exhibited diurnal patterns during earlier LD entrainment, was greater than 24 h, which became shorter than 24 h after 6-9 days of free-run in DD. The patterns of activity under LD cycles and the turn-around of activity patterns in DD regime suggest that these ants are shift workers in their respective colonies, and they probably use their circadian clocks for this purpose. Circadian plasticity thus appears to be a general strategy of the media workers of the ant species C. compressus to cope with the challenges arising due to their roles in the colony constantly exposed to a fluctuating environment.     

Altered circadian rhythm reentrainment to light phase shifts in rats with low levels of brain angiotensinogen

In this study, we aimed to investigate the adaptation of blood pressure (BP), heart rate (HR), and locomotor activity (LA) circadian rhythms to light cycle shift in transgenic rats with a deficit in brain angiotensin [TGR(ASrAOGEN)]. BP, HR, and LA were measured by telemetry. After baseline recordings (bLD), the light cycle was inverted by prolonging the light by 12 h and thereafter the dark period by 12 h, resulting in inverted dark-light (DL) or light-dark (LD) cycles. Toward that end, a 24-h dark was maintained for 14 days (free-running conditions). When light cycle was changed from bLD to DL, the acrophases (peak time of curve fitting) of BP, HR, and LA shifted to the new dark period in both SD and TGR(ASrAOGEN) rats. However, the readjustment of the BP and HR acrophases in TGR(ASrAOGEN) rats occurred significantly slower than SD rats. The LA acrophases changed similarly in both strains. When light cycle was changed from DL to LD by prolonging the dark period by 12 h, the reentrainment of BP and LA occurred faster than the previous shift in both strains. The readjustment of the BP and HR acrophases in TGR(ASrAOGEN) rats occurred significantly slower than SD rats. In free-running conditions, the circadian rhythms of the investigated parameters adapted in TGR(ASrAOGEN) and SD rats in a similar manner. These results demonstrate that the brain RAS plays an important role in mediating the effects of light cycle shifts on the circadian variation of BP and HR. The adaptive behavior of cardiovascular circadian rhythms depends on the initial direction of light-dark changes.     

Vitamin B12 accelerates re-entrainment of activity rhythms in rats.

The effects of methyl vitamin B12 (5-6 mg/kg, p.o.) on the entrainment of circadian running wheel activity rhythm to a new lighting schedule were measured in rats. After the light-dark (LD) cycle was abruptly reversed, rats given vitamin B12 took less time to entrain their circadian locomotor activity rhythm to the new cycle than did controls. This result indicates that vitamin B12 accelerates the reentrainment of the mammalian circadian activity rhythm following an abrupt change in the environmental LD cycle.