Single injections of triazolam,a short-acting benzodiazepine,lengthen the period of the circadian activity rhythm in golden hamsters

Single injections of the benzodiazepine, triazolam, induce phase shifts and cause a lengthening of the circadian activity rhythm in the golden hamster. The effect of triazolam on period depends on the phase of injection, but is not dependent on the direction of the phase shifts. Triazolam injections caused increases in period that were associated with phase advances as well as phase delays in the activity rhythm. This relationship between triazolam-induced phase shifts and changes in period is different from the relationship between light-induced phase shifts and period changes.     

Beta-methyl carboline, a benzodiazepine inverse agonist, attenuates the effect of triazolam on the circadian rhythm of locomotor activity

The benzodiazepine triazolam, the benzodiazepine inverse agonist, beta-methyl carboline (beta-CCM) or both, were administered to adult male hamsters under conditions of constant light. When given alone, triazolam induced phase advances in the circadian activity rhythm of about 90 min, while beta-CCM when given alone, had no effect on phase of the activity rhythm. However, when triazolam and beta-CCM were given at the same time, the magnitude of the phase advances induced by triazolam were attenuated to about 30 min. These data, in conjunction with previous results, provide pharmacological evidence for a GABAergic system involved in the regulation of a central circadian pacemaker.     

β-Methyl carboline,a benzodiazepine inverse agonist,attenuates the effect of triazolam on the circadian rhythm of locomotor activity

Summary The benzodiazepine triazolam, the benzodiazepine inverse agonist, -methyl carboline (-CCM) or both, were administered to adult male hamsters under conditions of constant light. When given alone, triazolam induced phase advances in the circadian activity rhythm of about 90 min, while -CCM when given alone, had no effect on phase of the activity rhythm. However, when triazolam and -CCM were given at the same time, the magnitude of the phase advances induced by triazolam were attenuated to about 30 min. These data, in conjunction with previous results, provide pharmacological evidence for a GABAergic system involved in the regulation of a central circadian pacemaker.     

Pentobarbital-induced phase shifts of circadian rhythms of locomotor activity are not mediated through stimulated activity in mice

The possibility that phase shifts of circadian rhythms of locomotor activity induced by pentobarbital injections are mediated through hyperactivity after recovery from the sedative condition was tested in DBA/2 mice. The mice were restrained for 3 h in a tube immediately after injections of pentobarbital at either CT 9 or CT 0. The results indicated that immobilization did not block the phase shifts, suggesting that pentobarbital-induced phase shifts are not due to increasing the level of activity.     

Pentobarbital-induced phase shifts of circadian rhythms of locomotor activity are not mediated through stimulated activity in mice

Summary The possibility that phase shifts of circadian rhythms of locomotor activity induced by pentobarbital injections are mediated through hyperactivity after recovery from the sedative condition was tested in DBA/2 mice. The mice were restrained for 3 h in a tube immediately after injections of pentobarbital at either CT 9 or CT 0. The results indicated that immobilization did not block the phase shifts, suggesting that pentobarbital-induced phase shifts are not due to increasing the level of activity.     

Seasonal variations in the nyctohemeral rhythm of plasma testosterone in the European badger Meles meles L

In the badger a seasonal sexual rhythm of the plasma testosterone is observed. There is also a nycthemeral rhythm of the testosterone secretion; during the regressed period of the testis this rhythm is bimodal with testosterone peaks during the light phase of the day; during the active period and "activity rhythm" with many transitorys peaks during the dark phase is added.     

Exogenous melatonin accelerates re-entrainment: Attenuation of the circadian rhythm of metabolic rate in the canary,Serinus canaria

Administration of melatonin in the drinking water (200 g/ml in 1% ethanol) decreased the time of re-entrainment of the circadian rhythm of the metabolic rate (measured as oxygen uptake) of domestic canaries (Serinus canaria) after 10-h delay phase shifts of the light-dark (LD) cycle by 1.3 days on average. Associated with faster re-entrainment, the amplitude of the metabolic rhythm was attenuated by 46% on, average on the first day after the shift as compared with about 25% in the controls. After re-entrainment, the amplitude of the metabolic rhythm during melatonin administration was about 23% lower than in the controls. The minimum resting metabolic rate increased by ca 5% on average during treatment with melatonin. The results are consistent with the hypothesis that constant high plasma levels of melatonin act on higher levels of the circadian oscillatory system rather than by directly affecting peripheral or central photoreceptors.     

Internal interactions within the human circadian system: the masking effect

In the realm of human circadian rhythms, the masking effect is defined as the change in the course of deep body temperature induced by changes in the degree of physical activity, or by the alteration between sleep and wake. This effect is particularly obvious during internal desynchronization where the rhythms of deep body temperature, and the sleep-wake sleep cycle - i.e. one of the masking factors - run with different periods. Every sleep onset is accompanied by a rapid drop, and wake onset by a rapid rise in deep body temperature, each one with an overshoot of about 50% of the steady state variations. When rhythms are calculated, with the dominant temperature period as the screening period, exclusively from data obtained during sleep episodes, on the one hand, and from those obtained exclusively during wake, on the other, two average cycles emerge: the 'sleep temperature curve' and the 'wake temperature curve'. Both run in parallel but are separated by the 'masking effect'. As derived from many experiments, the mean masking effect amounts to 0.28 +/- 0.06 degree C. The masking effect also depends to some extent on the phase of the temperature rhythm; it is larger than average around the temperature maximum and during the descending phase of the temperature cycle, where the alertness commonly is highest and the probability to sleep, in general, and the REM sleep propensity, in particular, are smaller than average. This also can be interpreted to indicate that the sleep temperature curve is phase advanced relative to the wake temperature curve; this, on the average, by 0.9 +/- 0.3 h. If the individually determined amount of masking is added to the temperature data obtained during sleep, or subtracted from the temperature data obtained during wake, a temperature curve emerges that can be thought of as being 'purified' of the masking effect. Analyses of this artificial curve allow estimation of that part of the internal interactions uninfluenced by the masking effect. On the average, about half of the amount of interaction between the rhythm of sleep-wake and that of deep body temperature is explained by the masking effect, whereas the other half is 'oscillatory interaction'. Both types of interaction are inherent and inseparable parts of the circadian clock mechanism, as can be deduced from model considerations.     

Chronobiology of sleep in humans

Periodic circadian (24-h) cycles play an important role in daily hormonal and behavioural rhythms. Usually our sleep/wake cycle, temperature and melatonin rhythms are internally synchronized with a stable phase relationship. When there is a desynchrony between the sleep/wake cycle and circadian rhythm, sleep disorders such as advanced and delayed sleep phase syndrome can arise as well as transient chronobiologic disturbances, for example from jet lag and shift work. Appropriately timed bright light is effective in re-timing the circadian rhythm and sleep pattern to a more desired time, ameliorating these disturbances. Other less potent retiming effects may also be obtained from the judicious use of melatonin and exercise.     

Photoperiodic regulation of mating behaviour in the linden bug,Pyrrhocoris apterus,is mediated by a brain inhibitory factor

Active inhibition of mating behaviour in a male insect is reported here for the first time. InPyrrhocoris apterus L. (Heteroptera), the most important inhibitory pathway runs from the pars intercerebralis (PI) of the brain and does not pass through the corpora allata. The inhibitory activity of the PI is promoted by short day conditions and suppressed by long days. As the effect of photoperiod is delayed, transfer procedures enabled us to record daily rhythms in mating behaviour during short days. While the extirpation of the PI results in a discrete phase shift of the long day rhythm, there is a much less significant phase shift after this operation during short days. Thus the PI has been shown to mediate the effect of photoperiod on both the inhibition and the rhythm of mating behaviour.     

Ontogenetic analysis of the theta rhythm during paradoxical sleep in rats]

In the rat, an ontogenetic study of theta rhythm during paradoxical sleep shows a clear evolution between the 14th and the 30th postnatal day. During this period, its mean frequency increases from 5 to 7 cycles per second, and its spectrum shows significant changes. These parameters (mean frequency and spectral components) of the theta rhythm could be a useful index of brain maturation in the rat.     

Model-as-replica,model-as-instrument: Representational power and contextual versatility in animal models

Existing scholarship on animal models tends to foreground either of the two major roles research organisms play in different epistemic contexts, treating their representational and instrumental roles separately. Based on an empirical case study, this article explores the changing relationship between the two epistemic roles of a research organism over the span of a decade, while the organism was used to achieve various knowledge ends. This rat model was originally intended as a replica of human susceptibility to cardiac arrest. In a fortunate stroke of serendipity, however, the experimenters detected the way mother-infant interactions regulated the pups’ resting cardiac rate. This intriguing outcome thus became the model’s new representational target and began driving the development of an experimental system. Henceforth, the model acquired an instrumental function, serving to detect and measure system-specific differences. Its subsequent development involved creating stimulus-response measures to explain and theorize those differences. It was this instrumental use of the model that pushed the experimenters into unchartered territory and conferred to the model an ability to adapt to varied epistemic contexts. Despite the prominence of this instrumental role, however, the model’s representational power continued to guide research. The model’s representational target was widened beyond heart rate to reflect other functional phenomena, such as behavioral activity and sleep/wake rhythm. The rat model was thus transformed from an experimental organism designed to instantiate cardiac regulation to a model organism taken to represent the development of a whole, intact animal under the regulatory influence of maternal care. This article examines this multifaceted transformation within the context of the salient shifts in modeling practice and variations in the model’s representational power. It thus explores how the relationship between the representational and instrumental uses of the model changed with respect to the varying exigencies of the investigative context, foregrounding its contextual versatility.     

A phase response curve for the locomotor activity rhythm of the rat

Summary A phase response curve was obtained for the locomotor activity rhythm of the rat,Mus norvegicus albicus, by interrupting a free-running rhythm with light signals of short duration. The response curve obtained was continuous and had the switch-over point at the position of 2 h before the acrophase, followed by the portion of advancing phase shift. The pattern of the curve was typical for the nocturnal rodent.     

Phase-dependent shift of free-running human circadian rhythms in response to a single bright light pulse

Responsiveness of free-running human circadian rhythms to a single pulse of bright light was examined in a temporal isolation unit. Bright light (5000 lx) of either 3 or 6 h duration, applied during the early subjective day, produced phase-advance shifts in both the sleep-wake cycle and the rhythm of rectal temperature; the light pulse had essentially no effect on the phase of the circadian rhythms, when it was introduced during the late subjective day or the early subjective night. The results indicate that bright light can reset the human circadian pacemaker.     

Effect of light at night on the pineal rhythm in N-acetyltransferase activity in the Syrian hamsterMesocricetus auratus

Summary Pineal N-acetyltransferase activity in the male Syrian hamster exhibited a daily rhythm; the maximal night-time value was 3.5-fold higher than the day-time value. When hamsters were exposed to light at night N-acetyltransferase declined within 30 min to 1/5 of its former activity. These results indicate that in the Syrian hamster the pineal melatonin rhythm may be regulated at least partly via changes in N-acetyltransferase activity.The authors are grateful to Mrs Marie Svobodová for her skillful technical assistance.     

Phase response curve to anisomycin in tau mutant hamsters.

Administration of the protein synthesis inhibitor, anisomycin, to wild type hamsters produces phase shifts in their circadian rhythms that have similarities to shifts produced by non-photic behavioral stimulation. A mutation that shortens the period of rhythms in hamsters results in altered responsiveness to non-photic input. However, responses of the mutants to anisomycin are unaffected: their phase response curve (PRC) for anisomycin is similar to that of wild types. This suggests that 1) anisomycin is not acting on mechanisms specifically involved in non-photic behavioral phase shifting, and 2) the mutation affects the non-photic input pathway or the pacemaker itself at a point that is upstream from anisomycin's site of action.     

Phase response curve to anisomycin intau mutant hamsters

Administration of the protein synthesis inhibitor, anisomycin, to wild type hamsters produces phase shifts in their circadian rhythms that have similarities to shifts produced by non-photic behavioral stimulation. A mutation that shortens the period of rhythms in hamsters results in altered responsiveness to non-photic input. However, responses of the mutants to anisomycin are unaffected: their phase response curve (PRC) for anisomycin is similar to that of wild types. This suggests that 1) anisomycin is not acting on mechanisms specifically involved in non-photic behavioral phase shifting, and 2) the mutation affects the non-photic input pathway or the pacemaker itself at a point that is upstream from anisomycin's site of action.     

Use of the specific benzodiazepine antagonist,Ro 15-1788, in studies of physiological dependence on benzodiazepines

Summary The specific benzodiazepine antagonist, Ro 15-1788, elicited withdrawal symptoms in squirrel monkeys, cats, rats and mice made tolerant and physically dependent by subchronic administration of high doses of diazepam, lorazepam or triazolam.     

Experimental evidence of the territorial defense,hypothesis in insular Blue Tits

Many insular vertebrates have unusually high population densities and are characterized by behavioural shifts including reduced territory size and reduced situation-specific aggressiveness. Compared to their mainland counterparts, Blue Tits on the island of Corsica exhibit many traits that fit the trends observed in crowded insular populations. We demonstrate from behavioural observations in aviaries and from hormone measurements that Corsican its are less aggressive than mainland ones. These shifts, as well as changes in reproductive patterns, support the defense hypothesis.     

Human slow wave sleep: A review and appraisal of recent findings,with implications for sleep functions,and psychiatric illness

Recent findings concerning human slow wave sleep (hSWS-stages 3+4; delta EEG activity) are critically reviewed. Areas covered include the significance of the first hSWS cycle; hSWS in extended sleep; relationship between hSWS, prior wakefulness and sleep loss; hSWS influence on sleep length; problems with hSWS deprivation; influence of the circadian rhythm; individual differences in hSWS, especially, age, gender and constitutional variables such as physical fitness and body composition. Transient increases in hSWS can be produced by increasing both the quality and quantity of prior wakefulness, with an underlying mechanism perhaps relating to the waking level of brain metabolism. Whilst there may also be thermoregulatory influences on hSWS, hypotheses that energy conservation and brain cooling are major roles for hSWS are debatable. hSWS seems to offer some form of cerebral recovery, with the prefrontal cortex being particularly implicated. The hSWS characteristics of certain forms of major psychiatric disorders may well endorse this prefrontal link.