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Restricted daily feeding entrains methamphetamine dependent circadian rhythm in SCN lesioned rats
$164 RESTRICTED DAILY FEEDING ENTRAINS METHAMPHETAMINE DEPENDENT CIRCADIAN RHYTHM IN SCN LESIONED RATS. SATO HONMA) KEN-ICHI HONMA) TSUTOMU HIROSHIGE) Department of Physiology) Hokkaido University School of Medicine, N-15) W-7 a Sapporo) 060 By continuous administration of methamphetamine, either through drinking water or implanted osmotic minipumps, SCN lesioned rats showed a robust rhythm with a circadian period in many physiological functions. This methamphetamine dependent rhythm has several characteristics similar to those of food-entrainable rhythm, which is another SCN independent rhythm. In the present experiment, restricted daily feeding (RF) was imposed on 6 SCN lesioned and blinded rats showing a stable rhythmicity in their spontaneous locomotor activity recorded by an Animex during methamphetamine treatment. Free access to food was limited to 4 or 6 h per day. Methamphetamine was dissolved in drinking water and given ad libitum. Methamphetamine concentration was initially 0.005%, which was increased to 0.01% or decreased to 0.0025% during the RF. The locomotor rhythm appearing with methamphetamine was phase-set by the RF. The phase angle difference between food presentation and activity onset became more negative with increasing dose of methamphetamine. The dose-dependent change in phase angle difference is most likely due to lengthening of the period of methamphetamine dependent rhythm, because there is a positive correlation between the methamphetamine dose and the period of locomotor rhythm. After termination of the RF schedule, the locomotor rhythm started to free-run from the phase set by the prior RF schedule. These results indicate that the methamphetamine dependent locomotor rhythm is entrained by RF.
C H A N G E S IN THE F R E E - R U N N I N G CIRCADIAN PARAMETERS ELICITED BY i . c . v . H I S T A M I N E . NOBUKO ITOWI*, ATSUSHI YAMATODANI, °KATSUYA NAGAI, °HACHIRO NAKAGAWA and HIROSHI WADA. Department o---f----P-harmacolo~y II__~, Faculty of M e l - ~ and °Division of P r o t e i f i - - - - M e t a - ~ ,
Institute for Protein Research, Osaka University, Osaka 530, Japan. Free-running rhythms elicited by fixed lighting condition reflect an organism's inherent circadian rhythm. Several drugs reportedly modulate these rhythms. We have previously reported the possibility of histaminergic modulation on the circadian rhythms of spontaneous activity and drinking behavior by depleting brain histamine. In this study, we examined the phase-shifting and period-changing effects of 10 jag histamine i.c.v, infused at every three hours of the subjective circadian times (CT) in each rat. Male Wistar rats were kept in continuous dark condition and their spontaneous activity and drinking behavior were automatically recorded by a tri-pod and a drop-counter. Circadian phase of both rhythms, estimated by their subjective dark on-set (CT-12), showed advance, delay or no change according to the subjective drug injection time. Phase-response curve was calculated from these results. Histamine injections during subjective light period (CT-0,3,6,9) tended to show phase-advance effect on both parameters, and reverse phase-delaying effects were seen by injections during subjective dark period (CT12,15,18,21). Period-lengthening and period-shortening effects on both circadian rhythms were also observed by i.c.v, histamine injection. These results, together with the existence of histaminergic terminals in the suprachiasmatic nucleus, the major oscillator of mammalian diurnal rhythms, indicate that neuronal histamine is involved in the modulation of biological rhythms.
C H A N G E S IN THE F R E E - R U N N I N G CIRCADIAN PARAMETERS ELICITED BY i . c . v . H I S T A M I N E . NOBUKO ITOWI*, ATSUSHI YAMATODANI, °KATSUYA NAGAI, °HACHIRO NAKAGAWA and HIROSHI WADA. Department o---f----P-harmacolo~y II__~, Faculty of M e l - ~ and °Division of P r o t e i f i - - - - M e t a - ~ ,
Institute for Protein Research, Osaka University, Osaka 530, Japan. Free-running rhythms elicited by fixed lighting condition reflect an organism's inherent circadian rhythm. Several drugs reportedly modulate these rhythms. We have previously reported the possibility of histaminergic modulation on the circadian rhythms of spontaneous activity and drinking behavior by depleting brain histamine. In this study, we examined the phase-shifting and period-changing effects of 10 jag histamine i.c.v, infused at every three hours of the subjective circadian times (CT) in each rat. Male Wistar rats were kept in continuous dark condition and their spontaneous activity and drinking behavior were automatically recorded by a tri-pod and a drop-counter. Circadian phase of both rhythms, estimated by their subjective dark on-set (CT-12), showed advance, delay or no change according to the subjective drug injection time. Phase-response curve was calculated from these results. Histamine injections during subjective light period (CT-0,3,6,9) tended to show phase-advance effect on both parameters, and reverse phase-delaying effects were seen by injections during subjective dark period (CT12,15,18,21). Period-lengthening and period-shortening effects on both circadian rhythms were also observed by i.c.v, histamine injection. These results, together with the existence of histaminergic terminals in the suprachiasmatic nucleus, the major oscillator of mammalian diurnal rhythms, indicate that neuronal histamine is involved in the modulation of biological rhythms.