Relationship of atypical melatonin rhythm with two circadian clock outputsin B6D2F(1) mice

Circadian rhythms in body temperature, locomotor activity, and the circadia n changes of plasma and pineal melatonin content were investigated in B6D2F (1) mice synchronized by 12 h of light and 12 h of darkness. During 8 wk co ntinuous 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 det ected. Mean plasma melatonin concentration rose steadily during the light s pan 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 content s displayed large and statistically significant circadian changes, with a c omposite rhythm of period (24 + 12 h). This mouse model has predominant pro duction and secretion of melatonin during the day. This possibly contribute s to a similar coupling between chronopharmacology mechanisms and the rest- activity cycle in these mice and in human subjects.