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1 Laboratoire "Rythmes Biologiques and Chronothérapeutique," Institut du Cancer et d'Immunogénétique et Université Paris XI, Hôpital Paul Brousse, 94807 Villejuif Cedex; 2 Institut de Recherches Internationales Servier, 92415 Courbevoie; and 3 Technologie Servier, 45000 Orléans, France
Circadian rhythms in body temperature, locomotor activity, and the circadian changes of plasma and pineal melatonin content were investigated in B6D2F1 mice synchronized by 12 h of light and 12 h of darkness. During 8 wk continuous recording, activity and temperature displayed a marked stable and reproducible circadian rhythm, with both peaks occurring near the middle of darkness. Both 24- and 12-h rhythmic components were also significantly detected. Mean plasma melatonin concentration rose steadily during the light span and reached a maximum (30.6 ± 10.0 pg/ml) at 11 h after light onset (HALO), then gradually decreased after the onset of darkness to a nadir (4.7 ± 0.4 pg/ml) at 20 HALO. Mean pineal content followed a pattern parallel to that of plasma concentration (peak at 11 HALO: 17.7 ± 1.0 pg/gland; trough at 17 HALO: 4.7 ± 1.0 pg/gland). In addition, a second sharp peak was observed at 21 HALO (20.2 ± 3.5 pg/gland). Plasma and pineal contents displayed large and statistically significant circadian changes, with a composite rhythm of period (24 + 12 h). This mouse model has predominant production and secretion of melatonin during the day. This possibly contributes to a similar coupling between chronopharmacology mechanisms and the rest-activity cycle in these mice and in human subjects.
circadian rhythms; body temperature; locomotor activity; pineal gland
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