| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
The Supradhiasmatic nucleus (SCN) of the hypothalamus represents the Biological Clock in mammals. In rodents, the ablation of the SCN results in total and irreversible loss of the circadian rhythms. However, by chronic administration of methamphetmine, robust rhythms with a circadian period appear in SCN-lesioned rats. An oscillatory mechanism is suggested to drive these rhythms. In this experiment, the localization and the function of this oscillator were studied.
Methods Adult Wistar female rats were used. Bilateral SCN were electrolytically lesioned and rats which showed no locomotor rhythms were used. Periods of rhythms were analyzed using a Chi-square periodogram.
Results Localization of the Oscillator Injection of the 6- hydoroxy dopamine (60HDA) into the lateral ventricle did not change the locomotor rhythm induced by methamphetamine. Locomotor rhythm also appeared in SCN-lesioned and methamphetamine treated rats after injecting 60HDA into the lateral hypothalamus or the nuclues a
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ccumbens. It is considered that the oscillator does not locate in the catecholaminergic pathways or the remaining catecholaminergic neurons are sufficient to drive rhythms. Function of the Oscillator outside the SCN Fourteen substances which have similar structure or pharmacological action to methamphetamine were administered to the SCN-lesioned rats. Among them, methylphenidate and Mazindol increased locomotor activity and induced rhythms In dose-dependent manner. It is concluded that the hyperlocomotive sate plays important role in generating and expressing the rhythms. Locomotor activities of SCN-intact and blinded rats were monitored by two different actograms, the Animex and the running-wheel in order to analyze the interaction of rhythms driven by the oscillators within and outside the SCN. Spontaneous locomotor activity monitored by an Animex showed relative coordination by methinphetamine treatment but the oscillator in the SCN was not affected. On the other hand, wheel-running activity seldom showed relative coordination methamphetamine treatment, while the period of SCN dependent oscillator was elongated. Wheel-running is considered to increase the coupling intensities between the two oscillators. Relation between Food- Entrainable Oscillator (FEO) By periodic food restriction (RF), rhythms appear in many physiological functions which are driven by the FEO. Because the FEO is known to locate outside the SCN, relation between these two SCN independent oscillators was studied. Rhythms appeared by methamphetamine in SCN lesioned rats-entrained to the RF. But the phase-relation to the RF schedule was different in these two rhythms. Mode of interaction between the light-entrainable rhythms was also different. Less
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