Circadian Rhythm of the Pupillary Response to Morphine and to Naloxone

Mice respond to morphine with characteristic mydriasis which is antagonized by naloxone. The present study presents data on the diurnal variation of these responses. The mydriatic response is at its highest level at 0800 and has a nadir at 2400. This effect is not influenced by ambient light conditions. The miotic response to naloxone in the morphine-dilated pupil is maximal between 1200 and 1600 and minimal at 0400. The curves of the responses to the two drugs, therefore, differ as do their acrophases. Pharmacokinetic factors are probably not responsible for the observed variations. It is speculated that these diurnal changes may reflect cyclic alteration in the affinity of the opiate receptors to agonists and antagonists, respectively, or in the number of available receptors.     

Circadian Rhythm in Pineal N-Acetyltransferase Activity: Rapid Phase Reversal and Response to Shorter than 24-Hour Cycles (IV)

N-Acetyltransferase (NAT) is an enzyme whose rhythmic activity in the pineal gland and retina is responsible for circadian rhythms in melatonin. The NAT activity rhythm has circadian properties such as persistence in constant conditions and precise control by light and dark. Experiments are reported in which chicks (Gallus domesticus), raised for 3 weeks in 12 h of light alternating with 12 h of dark (LD12:12), were exposed to 1-3 days of light-dark treatments during which NAT activity was measured in their pineal glands. (a) In LD12:12, NAT activity rose from less than 4.5 nmol/pineal gland/h during the light-time to 25-50 nmol/pineal gland/h in the dark-time. Constant light (LL) attenuated the amplitude of the NAT activity rhythm to 26-45% of the NAT activity cycle in LD12:12 during the first 24 h. (b) The timing of the increase in NAT activity was reset by the first full LD12:12 cycle following a 12-h phase shift of the LD12:12 cycle (a procedure that reversed the times of light and dark by imposition of either 24 h of light or dark). This result satisfies one of the criteria for NAT to be considered part of a circadian driving oscillator. (c) In less than 24-h cycles [2 h of light in alternation with 2 h of dark (LD2:2), 4 h of light in alternation with 4 h of dark (LD4:4), and 6 h of light in alternation with 6 h of dark (LD6:6)], NAT activity rose in the dark during the chicks' previously scheduled dark-time but not the previously scheduled light-time of LD12:12. In a cycle where 8 h of light alternated with 8 h of dark (LD8:8), NAT activity rose in both 8-h dark periods, even though the second one fell in the light-time of the prior LD12:12 schedule.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circadian Rhythm of Blood Pressure: Internal and External Time Triggers

Diurnal blood pressure (BP) fluctuations are superimposed by a 24-h rhythm with usually lower levels during the night and higher levels during the day. In contrast to other rhythmic bioparameters, the diurnal BP rhythm is largely dependent on activity and sleep rather than on clock time. This has been demonstrated by the BP characteristics after shifted sleeping and working phases, during transition from sleep to wakefulness, and by the influence of sleep and activities on the 24-h BP curve during normal daily routines. Whereas the circadian rhythm of BP is predominantly governed by external time triggers, endogenous rhythmic-ity can only be detected by time microscopic analysis or in conditions where effects of external time triggers are almost excluded.     

Circadian Rhythm of Activity in Japanese Quail in Constant Darkness: Variability of Clarity and Possibility of Selection

In conditions of constant darkness, interindividual variability in the clarity of circadian rhythmicity was observed in sexually immature young quail, with birds classified as more or less rhythmic or arrhythmic. The relative clarity of this circadian rhythm was observed on the actograms by measurement of the autocorrelation coefficient ratio over 12 cycles. Autocorrelation coefficients were calculated from sequential series of total activity over 12-minute periods. Crosses of selected phenotypes with different clarities of rhythmicity were conducted in order to study the possibility of selection of this characteristic. From a random population (N = 42, twice), pairs of the most rhythmic birds (3 families), and pairs of arrhythmic birds (4 families) were reared. Autocorrelation coefficient ratios of Fl birds from rhythmic families (N = 54) were greater than those of Fl birds (N = 48) from arrhythmic families (t-test, p <. 0001). These ratios in offspring were significantly correlated with that of the mean parent of each clutch of siblings (N= 102, r =.35, p =. 0003). This result was maintained in a second generation (F2) of birds, for which significant differences in expressed rhythmicity were observed. That is, autocorrelation coefficient ratios of F2 birds from two rhythmic families (TV = 30) were greater than those of F2 birds from arrhydimic families (N = 20) (t-test, p =. 039). Comparison of F2 outbred and inbred birds from rhythmic pairs showed greater values of autocorrelation coefficient ratios in the case of inbred birds (N = 16) than for outbred birds (N = 30; t-test, p =. 036). There was no difference between outbred (N = 20) and inbred birds (N = 15) from arrhythmic pairs. Therefore, selection of a rhythmic strain seems possible, whereas crosses between two arrhythmic birds may also give rise to rhythmic birds. Comparisons between rhythmic birds of different families did not show differences in the free-running period of the circadian rhythm, which is true also for rhythmic birds bred from two arrhythmic parents. Therefore, our selection procedure did not seem to be based on the characteristics of the pacemaker itself, but rather on a downstream event. Although the parents were not selected on the basis of quantity of activity per cycle or on the duration of the active phase, significant differences among the offspring of different families were shown. (Chronobiology International, 75(3), 219–230, 1998)     

Circadian Rhythm of Blood Pressure: Internal and External Time Triggers

Diurnal blood pressure (BP) fluctuations are superimposed by a 24-h rhythm with usually lower levels during the night and higher levels during the day. In contrast to other rhythmic bioparameters, the diurnal BP rhythm is largely dependent on activity and sleep rather than on clock time. This has been demonstrated by the BP characteristics after shifted sleeping and working phases, during transition from sleep to wakefulness, and by the influence of sleep and activities on the 24-h BP curve during normal daily routines. Whereas the circadian rhythm of BP is predominantly governed by external time triggers, endogenous rhythmicity can only be detected by time microscopic analysis or in conditions where effects of external time triggers are almost excluded.     

Circadian Rhythms of Enzymes' Activity in Mice Tissues During Exposure to Continuous Illumination

Activity rhythms of enzymes were determined in various tissues of C57BL/6J male mice. The determinations were carried out on mice which were kept in 14 hr light: 10 hr dark regimen, and on day 2, day 5 and day 21 during exposure to continuous illumination. Locomotor activity rhythms were followed in light: dark and up to the seventh day in constant light. All the activities exhibited a significant circadian rhythm in the light: dark regimen. During the exposure to continuous illumination, the locomotor activity exhibit a free running circadian rhythm with a consistent 24 hr and 40 min, major period component. At the same time recording the rhythms of enzyme activity; enzymes exhibited various formats of response which differed from those of the locomotor activity. The results suggest that rhythms of enzyme activity, as well as the desynchronization of the rhythms, are not enzyme specific.     

Action Spectrum for Resetting the Circadian Phototaxis Rhythm in the CW15 Strain of Chlamydomonas: I. Cells in Darkness

We have developed protocols for phase shifting the circadian rhythm of Chlamydomonas reinhardtii by light pulses. This paper describes the photobiology of phase-resetting the Chlamydomonas clock by brief (3 seconds to 15 minutes) light pulses administered during a 24 hour dark period. Its action spectrum exhibited two prominent peaks, at 520 and 660 nanometers. The fluence at 520 nanometers required to elicit a 4 hour phase shift was 0.2 millimole photon per square meter, but the pigment that is participating in resetting the clock under these conditions is unknown. The fluence needed at 660 nanomoles to induce a 4 hour phase shift was 0.1 millimole photon per square meter, which is comparable with that needed to induce the typical low fluence rate response of phytochrome in higher plants. However, the phase shift by red light (660 nanometers) was not diminished by subsequent administration of far-red light (730 nanometers), even if the red light pulse was as short as 0.1 second. This constitutes the first report of a regulatory action by red light in Chlamydomonas.     

血压昼夜节律特征及其分子调控机制

正常血压具有典型的昼夜节律特征。血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系,是独立于血压水平的重要致病因素。血压昼夜节律的产生和维持与时钟基因的周期性表达有关。时钟基因bmal1、per2是体内生物钟系统运行的关键基因,其表达水平和节律变化直接调节血压的昼夜节律。     

血压昼夜节律特征及其分子调控机制

正常血压具有典型的昼夜节律特征。血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系,是独立于血压水平的重要致病因素。血压昼夜节律的产生和维持与时钟基因的周期性表达有关。时钟基因bmal1、per2是体内生物钟系统运行的关键基因,其表达水平和节律变化直接调节血压的昼夜节律。     

Dim Nighttime Illumination Interacts With Parametric Effects of Bright Light to Increase the Stability of Circadian Rhythm Bifurcation in Hamsters

The endogenous circadian pacemaker of mammals is synchronized to the environmental day by the ambient cycle of relative light and dark. The present studies assessed the actions of light in a novel circadian entrainment paradigm where activity rhythms are bifurcated following exposure to a 24-h light:dark:light:dark (LDLD) cycle. Bifurcated entrainment under LDLD reflects the temporal dissociation of component oscillators that comprise the circadian system and is facilitated when daily scotophases are dimly lit rather than completely dark. Although bifurcation can be stably maintained in LDLD, it is quickly reversed under constant conditions. Here the authors examine whether dim scotophase illumination acts to maintain bifurcated entrainment under LDLD through potential interactions with the parametric actions of bright light during the two daily photophases. In three experiments, wheel-running rhythms of Syrian hamsters were bifurcated under LDLD with dimly lit scotophases, and after several weeks, dim scotophase illumination was either retained or extinguished. Additionally, “full” and “skeleton” photophases were employed under LDLD cycles with dimly lit or completely dark scotophases to distinguish parametric from nonparametric effects of bright light. Rhythm bifurcation was more stable in full versus skeleton LDLD cycles. Dim light facilitated the maintenance of bifurcated entrainment under full LDLD cycles but did not prevent the loss of rhythm bifurcation in skeleton LDLD cycles. These studies indicate that parametric actions of bright light maintain the bifurcated entrainment state; that dim scotophase illumination increases the stability of the bifurcated state; and that dim light interacts with the parametric effects of bright light to increase the stability of rhythm bifurcation under full LDLD cycles. A further understanding of the novel actions of dim light may lead to new strategies for understanding, preventing, and treating chronobiological disturbances. (Author correspondence: jevans@msm.edu)     

Cerebroid Ganglion is the Presumptive Pacemaker of the Circadian Rhythm of Electrical Response to Light in the Crayfish

One of the most widely studied circadian rhythms in invertebrates is that of light responsiveness whose underlying mechanisms seem to involve different groups of oscillators which act as pacemakers. Although, in crayfish, there are clear circadian rhythms in the electroretinogram (ERG) amplitude, the precise location of the pacemaker system driving this rhythm is uncertain. Some data suggest that the circadian pacemaker could be located in a group of neurosecretory cells of the supraesophageal ganglion (the cerebroid ganglion or brain) and that the sinus gland plays a determinant role in the generation and expression of this rhythm through periodic release of pigment-dispersing hormone (PDH). The aim of this work is to examine the role of the brain in the expression of the ERG circadian activity. The hypothesis we test is that the electrical activity at the brain level has a circadian behavior in the firing pattern of spontaneous multiunit activity (MUA) and in visual evoked potentials (VEPs). The results indicate that there are robust circadian rhythms in both MUA, recorded from several regions of the brain, and in the averaged VEPs recorded from the protocerebrum area. These rhythms are 180° out of phase to one another. The rhythm of VEPs showed a main peak at midnight which was in close phase relationship with the ERG amplitude rhythm.     

Circadian Rhythm of Blood Pressure in Congestive Heart Failure and Effects of ACE Inhibitors

In 33 patients with heart failure (NYHA 11-III), the 24-h blood pressure rhythm was examined before and after the titration period of two ACE inhibitors. Blood pressure was measured by the oscillometric method using the blood pressure monitor 90202 from SpaceLabs, Inc. The measurements were taken from 06:OO to 22:OO h every 20 min and from 22:00 to 06:00 h every hour. Patients were randomized to therapy with either captopril (group 1, n = 17) or enalapril (group 2, n = 16). The average daily dosage of captopril was 41 ± 3 mg given in three divided doses (08:00, 12:00, and 17:00 h). The mean dose of enalapril was 8 ± 1 mg once daily (08:00 h). Serum electrolytes, serum creatinine, and plasma renin activity were measured before and during therapy with both ACE inhibitors. Twenty-four-hour blood pressure measurements were taken before and on the fifth day of treatment with ACE inhibitors. Both groups were not different with respect to the degree of heart failure, the concomitant medication, and the 24-h profiles of blood pressure and heart rate before initiation of ACE inhibition. The 24-h blood pressure values on day 5 were consistently below the pretreatment values (p < 0.005) in both groups. Both groups did not differ significantly during ACE inhibition in their 24-h blood pressure and heart rate profiles. In both groups, the mesor of the systolic and diastolic blood pressure decreased significantly by the same degree (by 4.7/5.1 mmg Hg in group 1 and 6.4/4.1 mm Hg in group 2). The systolic/diastolic blood pressure amplitude decreased slightly in both groups. Before treatment, serum sodium, potassium, and creatinine were within the normal range. The increase in potassium (0.5 ± 0.1 mmol/L) reached statistical significance (p < 0.01) only in the captopril group, whereas it was not significant in the enalapril group (0.1 ± 0.1 mmol/L). Serum creatinine was not significantly altered by both ACE inhibitors. No relationship could be found between the changes in serum potassium or creatinine and the mean of the 24-h blood pressure values during ACE inhibition. Captopril and enalapril showed comparable blood pressure profiles and similar effects on renal function at the end of the titration on day 5. It can therefore be concluded that the effects on blood pressure rhythm and renal function are similar with a single daily dose of enalapril compared to captopril given three times daily.     

Response of Respiration of Tobacco Leaves in Light and Darkness and the CO(2) Compensation Concentration to Prior Illumination and Oxygen

The course of respiration in control leaves of tobacco (Nicotiana tabacum L.) that were illuminated 4 to 5 hours and then darkened 0.25 to 10 hours and in tobacco leaves starved of carbohydrate by 14 hours or more of darkness was measured as CO₂ efflux in light and darkness into CO₂-free atmospheres containing 0.04, 2.23, 21, 40, and 100% O₂.     

强光照和全黑暗条件下荒漠沙蜥视网膜内GAP-43表达的免疫组织化学

采用免疫组织化学技术研究了在强光照和全黑暗条件下荒漠沙蜥(Phrynocephalus prezewalskic)视网膜内生长相关蛋白GAP-43的表达变化。结果表明,在正常光照条件下,视网膜内GAP-43阳性表达部位主要存在于内网层;强光照条件下,GAP-43免疫染色部位主要出现在内网层、节细胞层和内核层的部分细胞核。在全黑暗条件下,在视纤维层和内网层呈阳性染色;提示视网膜在不同环境条件下GAP-43的不同定位,可能与其在相应的环境下参与不同的视觉功能有关。     

Circadian Rhythm of Outside-Nest Activity in Wild (WWCPS), Albino and Pigmented Laboratory Rats

The domestication process of the laboratory rat has been going on for several hundred generations in stable environmental conditions, which may have affected their physiological and behavioural functions, including their circadian system. Rats tested in our ethological experiments were laboratory-bred wild Norway rats (WWCPS), two strains of pigmented laboratory rats (Brown Norway and Long Evans), and two strains of albino rats (Sprague-Dawley and Wistar). Rats were placed in purpose-built enclosures and their cycle of activity (time spent actively outside the nest) has been studied for one week in standard light conditions and for the next one in round-the-clock darkness. The analysis of circadian pattern of outside-nest activity revealed differences between wild, pigmented laboratory, and albino laboratory strains. During daytime, albino rats showed lower activity than pigmented rats, greater decrease in activity when the light was turned on and greater increase in activity when the light was switched off, than pigmented rats. Moreover albino rats presented higher activity during the night than wild rats. The magnitude of the change in activity between daytime and nighttime was also more pronounced in albino rats. Additionaly, they slept outside the nest more often during the night than during the day. These results can be interpreted in accordance with the proposition that intense light is an aversive stimulus for albino rats, due to lack of pigment in their iris and choroid, which reduces their ability to adapt to light. Pigmented laboratory rats were more active during lights on, not only in comparison to the albino, but also to the wild rats. Since the difference seems to be independent of light intensity, it is likely to be a result of the domestication process. Cosinor analysis revealed a high rhythmicity of circadian cycles in all groups.     

Effect of Continuous Infusion of Anti-L1 Antibody into the Third Cerebral Ventricle above the Suprachiasmatic Nucleus on the Circadian Rhythm of Locomotor Activity in Rats

During an investigation into the role of the neural cell adhesion molecules such as L1 and NCAM in the generation mechanism of circadian rhythms, we observed that L1-like immunoreactive substance is expressed in the hypothalamic suprachiasmatic nucleus (SCN). Therefore, we examined the effect of continuous infusion of anti-L1 antibody into the third cerebral ventricle above the SCN using an Alzet osmotic minipump, on the circadian rhythm of locomotor activity in rats under constant red dim light (less than 1 lx) condition, in order to elucidate the role of L1 in the mechanism of circadian rhythm. Continuous infusion of intact rabbit IgG into the third cerebral ventricle above the SCN, which was done as a control experiment, shifted the phase of the free-running circadian rhythm and reduced daily locomotor activity for an initial few days, however, it did not eliminate the circadian rhythm. In contrast, continuous infusion of anti-L1 antibody temporarily disrupted the circadian rhythm during the infusion period. Furthermore, the infusion of the anti-L1 antibody but not that of control IgG caused a change in the SCN conformation, from which it appeared that SCN neurons displaced in dorsal direction, 4 days after the start of the infusion. These findings suggest that the cell adhesion molecule, L1, might be involved in the generation and/or transduction of the time signal of the circadian rhythm in the SCN.     

Effects of Prolonged Exposure to Darkness on Circadian Photic Responsiveness in the Mouse

Circadian rhythms in mammals are generated by an endogenous pacemaker but are modulated by environmental cycles, principally the alternation of light and darkness. Although much is known about nonparametric effects of light on the circadian system, little is known about other effects of photic stimulation. In the present study, which consists of a series of five experiments in mice, various manipulations of photic stimulation were used to dissect the mechanisms responsible for a variation in the magnitude of light-induced phase-shifts that results from prolonged exposure to darkness. The results confirmed previous observations that prolonged exposure to darkness causes an increase in the magnitude of phase shifts (both phase advances and phase delays) evoked by discrete light pulses. The results also indicated that the increase in responsiveness results from the lack of exposure to light per se and not from collateral effects of exposure to constant darkness such as the lack of previous entrainment. The lack of exposure to light causes the circadian system to undergo a process of dark adaptation similar to dark adaptation in the visual system but with a much slower temporal course. The results suggest that circadian dark adaptation may take place at the retinal level, but it is not clear whether it involves a change in the sensitivity or maximal responsiveness of the system.     

The Potassium Content of Gonyaulax polyedra and Phase Changes in the Circadian Rhythm of Stimulated Bioluminescence by Short Exposures to Ethanol and Valinomycin

A circadian rhythm in the intracellular level of K⁺ in Gonyaulax polyedra is reported. When axenic cultures of Gonyaulax in continuous light (60-75 fot candles) are exposed for 4 hours to 0.1 or 0.2% ethanol, the subsequent free-running rhythm in stimulated bioluminescence is phase-shifted, the amount and direction of the shift being dependent on the time in the circadian cycle when cells are treated. The phase-response curve for ethanol closely resembles that for light in similarly maintained cells. When valinomycin (0.1 or 0.2 μg ml⁻¹) is present in addition to ethanol, the phase of the bioluminescence rhythm is returned to that of an untreated cell suspension. Valinomycin thus negates the effect of ethanol on phase. The intracellular K⁺ level immediately after treatment of a cell suspension for 4 hours with ethanol (0.1%) is about half that of untreated cells. If valinomycin (0.1 μg ml⁻¹) is also present during the 4-hour treatment, the intracellular K⁺ is only slightly lower than in untreated cells. Increasing the external concentration of K⁺ or Na⁺ for 4 hours has no effect on the rhythm of stimulated bioluminescence. These results are interpreted as support for the hypothesis that the mechanism by which circadian oscillations are generated involves changes in membrane properties.     

Effect of Continuous Infusion of Anti-L1 Antibody into the Third Cerebral Ventricle above the Suprachiasmatic Nucleus on the Circadian Rhythm of Locomotor Activity in Rats

During an investigation into the role of the neural cell adhesion molecules such as L1 and NCAM in the generation mechanism of circadian rhythms, we observed that L1-like immunoreactive substance is expressed in the hypothalamic suprachiasmatic nucleus (SCN). Therefore, we examined the effect of continuous infusion of anti-L1 antibody into the third cerebral ventricle above the SCN using an Alzet osmotic minipump, on the circadian rhythm of locomotor activity in rats under constant red dim light (less than 1 lx) condition, in order to elucidate the role of L1 in the mechanism of circadian rhythm. Continuous infusion of intact rabbit IgG into the third cerebral ventricle above the SCN, which was done as a control experiment, shifted the phase of the free-running circadian rhythm and reduced daily locomotor activity for an initial few days, however, it did not eliminate the circadian rhythm. In contrast, continuous infusion of anti-L1 antibody temporarily disrupted the circadian rhythm during the infusion period. Furthermore, the infusion of the anti-L1 antibody but not that of control IgG caused a change in the SCN conformation, from which it appeared that SCN neurons displaced in dorsal direction, 4 days after the start of the infusion. These findings suggest that the cell adhesion molecule, L1, might be involved in the generation and/or transduction of the time signal of the circadian rhythm in the SCN.