Ken-Ichi Honma

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

Entrainment of human circadian rhythms by artificial bright light cycles

Artificial bright light cycles (LD 8∶16) of about 5000 lux during the light period were applied to two subjects in a temporal isolation unit, who had shown free-running circadian rhythms in sleep-wakefulness and rectal temperature. The circadian rhythms were successfully entrained by the artificial light cycle, but the phase relation of the rhythms to the light cycle was substantially different between the two subjects. The result indicated that the artificial bright lights are able to reset human circadian rhythms.

Rhythms in behaviors, body temperature and plasma corticosterone in SCN lesioned rats given methamphetamine

In aperiodic rats with lesions in the suprachiasmatic nuclei (SCN), rhythms with a circadian period in spontaneous locomotion, wheel-running, feeding, drinking, body temperature and plasma corticosterone were restored by chronic administration of methamphetamine. These rhythms were not entrained by a light-dark cycle. Wheel-running, feeding and drinking rhythms in individual rats were in phase in terms of ultradian bout as well as circadian fluctuation. Rhythms of the intraperitoneal temperature appeared accompanying the spontaneous locomotor rhythm. The phase relation between the two rhythms was similar to that of SCN dependent rhythms. Plasma corticosterone also fluctuated in a circadian fashion. The corticosterone peak preceded the activity onset of locomotor rhythm by a few hours, which was similar to the phase relation observed in the SCN intact animals. It is concluded that the oscillatory mechanism underlying the spontaneous locomotor rhythm in SCN lesioned and methamphetamine treated rats drives also other physiological rhythms. The phase-relations among them were similar to those of rhythms driven by the circadian pacemaker in the SCN.

Light suppression of nocturnal pineal and plasma melatonin in rats depends on wavelength and time of day

Effects of light on the pineal and plasma melatonin were examined in Wistar and Long-Evans rats at two different times in the dark phase (light off from 18.00 h to 06.00 h) using lights of two different monochromatic wavelengths but with the same irradiance. The green light pulse (520 nm) given at 24.00 h suppressed the pineal and plasma melatonin to the day-time level for at least 2 h, while the red light (660 nm) pulse given at the same time of the day suppressed pineal melatonin only transiently and did not suppress the plasma melatonin at all. Both green and red lights given at 4.00 h suppressed the pineal and plasma melatonin to a similar extent. The results demonstrated that the suppression of melatonin by light depends on the wavelength of light and the circadian phase.

Seasonality in human sleep.

The timing of sleep and sleep EEG parameters in 10 healthy male subjects were investigated in four seasons under controlled conditions. The phase of nocturnal sleep was delayed about one and a half hours in winter as compared to that in summer. The duration of stage 4 sleep decreased and REM sleep increased significantly in winter compared with summer. The seasonality in the timing of sleep can be explained by photoperiodic time cues, but the changes in sleep EEG parameters are diffucult to explain in terms of photoperiod.

Methamphetamine induced locomotor rhythm entrains to restricted daily feeding in SCN lesioned rats

Rats were lesioned in the SCN and treated with methamphetamine dissolved in drinking water. A robust rhythm appeared in spontaneous locomotor activity which was not affected by blinding. Periodic food restriction (RF) of a 24 hr period was imposed on SCN lesioned rats with free-access to food for 4 or 6 hr per day, while water was given ad lib. The locomotor rhythm induced by methamphetamine treatment was phase-set by RF immediately in most cases but with transients in some. The phase-angle difference (psi) between food presentation and the activity onset became more negative by increasing the dose of methamphetamine. Because there was a positive correlation between methamphetamine dose and the period of locomotor rhythm, the change in psi was most likely due to lengthening of the period. After the termination of the RF schedule, the locomotor rhythm started to free-run from the prior phase set by RF. These results indicate that the methamphetamine dependent locomotor rhythm entrains to RF.

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

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.

Methamphetamine effects on rat circadian clock depend on actograph

Methamphetamine effects on the rest-activity rhythm were examined in 12 blinded rats using two different actographs, an Animex and a running-wheel. D-Methamphetamine was administered chronically by dissolving it in drinking water. During methamphetamine treatment, the rest-activity rhythm measured by an Animex showed a clear sign of relative coordination in addition to the general enhancement of activity level. Analyses of pre- and posttreatment activity rhythms revealed that neither the phase nor the period was affected by methamphetamine treatment. On the other hand, the circadian period was lengthened by methamphetamine treatment when locomotor activity was measured by a running-wheel. These results confirmed our previous findings that the chronic treatment of methamphetamine modified the expression of the circadian rhythms but did not affect the underlying oscillation when measured by an Animex, and further indicated that methamphetamine could affect the underlying oscillation when rats had free access to a running-wheel. It is concluded that the effects of methamphetamine on the circadian clock depend on actograph.

SCN-independent circadian oscillators in the rat

In this short overview, features of the two suprachiasmatic nucleus (SCN)-independent oscillators are described. One is restricted daily feeding (RF)-associated oscillator and the other is methamphetamine-dependent oscillator. We found that both oscillators have free-running period of circadian range, and express themselves in the special state of energy supply or energy deficiency. The expression of the RF-associated oscillator depends heavily on the catecholaminergic input from the medulla, whereas the methamphetamine-dependent oscillator appears to depend on the sympathomimetic effects of the drug. It is plausible that overt rhythms of both oscillators are complex, mainly because of the interaction of hourglass principle with circadian clock mechanism.

Locomotor rhythms induced by methylphenidate in suprachiasmatic nuclei-lesioned rats

A robust locomotor activity rhythm with a circadian period appeared by chronic treatment with methylphenidate or methamphetamine in the suprachiasmatic nuclei (SCN)-lesioned rats whose circadian rhythms had been abolished. The appearance of the rhythmicity was accompanied by an increase in the activity level. However, significant circadian periods were detected only in rats whose locomotor activity increased more than 200% of the pretreatment levels. An increase in the activity level is necessary to generate and/or express the circadian locomotor rhythm in SCN-lesioned rats and there seems to be a threshold.