A chronobiological study of the pathogeneses and treatments of human circadian rhythm disorders using animal models

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A. Model of acute time-zone change and triazolam: The phase-shifting effect of triazolam (5 mg i.p.) on free-running circadian rhythms of ambulation and drinking was examined in rats. No consistent relationship between the circadian times of triazolam injection and the phase shifts was found. This result for rats was different from that for hamsters reported by Turek et al. (1986). After 5 mg triazolam was i.p. injected to rats at 5 different times of the transition period for 6-h phase advance of a 12:12 light- dark cycle, the number of days needed for re-entrainment of circadian rhythms was determined. The effect of time of triazolam injection on the number of days for re-entrainment was different among circadian rhythms of ambulation, drinking, body temperature and sleep. These results suggest that there is a species difference in the phase-shifting effect of triazolam.B. Model of seasonal affective disorder (SAD) and bright light exposure: Photoperiodism is supposed to be involved … More in the pathogenesis of SAD. In search of an animal model for SAD, we examined the effects of ambient photoperiods and illuminances on the circadian rhythms of locomotor activity and drinking in male rats. On the short days (LD ratio = 0.5) with the lowest illuminance (5 1x), acrophase was most delayed and activity time was most prolonged in comparison to the long and equal days with higher illuminances. We examined the effect of the timing of a bright light exposure (1 h, 2000 1x) on the acrophase of behavioral circadian rhythm. When bright light was given at the beginning or at the end of the light period, acrophaie was slightly (less than 1 h) shifted. When bright light was given 3 h before the onset of the light period to simulate the timing of morning bright light exposure for SAD, acrophase was markedly (5 h) advanced. From these results, we analogized in SAD patients that circadian rhythm would be phase-delayed in winter, and morning bright light would show a therapeutic effect by phase-advancing the delayed circadian rhythm. Less