
Figure 1
Circadian rhythms of pineal 5-HT, N-acetylserotonin (NAS), and melatonin in a LEW rat over a 5-day period. A. 5-HT (pink), NAS (blue), and melatonin (yellow) profiles of a single LEW rat are shown for 5 consecutive cycles. In this and all subsequent figures, the shaded gray areas represent the dark period (18:00 h to 6:00 h). The daily boundaries were arbitrarily set at 13:00 h for ease of comparison. B. 5-HT (top panel), NAS (middle panel), and melatonin (bottom panel) data from each 24 h period (13:00 h to 13:00 h) were normalized to its nocturnal maximum values and superimposed together. Pineal secretory activities of 5-HT, NAS, and melatonin in different cycles were represented with different colors, and the values of 5-HT, NAS, and melatonin from the same cycle were represented with the same colors. The horizontal dashed lines represent onset phase of 5-HT (top panel, 80%), NAS (middle panel, 20%), and melatonin (bottom panel, 20%). C. Profiles of 5-HT (pink), NAS (blue), and melatonin (yellow) of the rat shown in B were superimposed in the same panel for a clearer comparison.

Figure 2
Circadian profiles of pineal 5-HT and melatonin secretion from multiple outbred SD and Wistar rats. A. Entrained profiles of 5-HT (upper panel) and melatonin (lower panel) secretion from 6 SD rats. All data points were normalized to the nocturnal peak values of each circadian cycle. Each rat is represented by a different color. 5-HT and melatonin secretion from the same rat is shown in the same color. B. Secretory activities of 5-HT (upper panel) and melatonin (lower panel) from 8 Wistar rats. C. Comparison of 5-HT (upper panel) and melatonin (lower panel) secretion profiles from SD (red) and Wistar (green) rats. D. Phase angle difference in MT-on is independent of pineal mechanisms. Norepinephrine (NE, 20 uM) was infused directly into the pineal gland of the rats ID2263 (pink) and ID2269 (blue) for 3.5 hrs (11:00 h-14:30 h; blue shaded area). Data for melatonin secretion were normalized to the nocturnal maximum of the first night.

Figure 3
Circadian profiles of pineal 5-HT and melatonin secretion from multiple inbred PVG and LEW rats. A. Entrained profiles of 5-HT (upper panel) and melatonin (lower panel) secretion from 4 PVG rats. All data points were normalized to the nocturnal peak values of each circadian cycle. Each rat is represented by a different color. 5-HT and melatonin secretion from the same rat is shown in the same color. B. Secretory activities of 5-HT (upper panel) and melatonin (lower panel) from 4 LEW rats. C. Comparison of 5-HT (upper panel) and melatonin (lower panel) secretion profiles from PVG (yellow) and LEW (blue) rats. D. Comparison of 5-HT (upper panel) and melatonin (lower panel) secretion profiles from all 4 strains of rats: SD (red), Wistar (green), PVG (yellow), and LEW (blue) rats. E. Phase angle difference in MT-on between PVG and LEW rats is independent of pineal mechanisms. Norepinephrine (NE, 20 uM) was infused directly into the pineal gland of 2 PVG (ID2294 and ID2297) and 2 LEW (ID2287 and ID2291) rats for 4 hrs (11:00 h-15:00 h; blue shaded area). Data for melatonin secretion at night were normalized to the nocturnal maximum, whereas data between 9:00 h and 15:00 h were normalized to the maximum levels stimulated by the norepinephrine (13:00 h-14:00 h). Compared to PVG rats, appearance of melatonin following norepinephrine stimulation was slightly delayed (10–20 min). This difference was due to the time needed to change drug-filled syringes.

Figure 4
Circadian profiles of pineal 5-HT and melatonin secretion from multiple outbred Syrian hamsters. A. Entrained profiles of 5-HT (upper panel) and melatonin (lower panel) secretion from 3 Syrian hamsters. All data points were normalized to the nocturnal peak values of each circadian cycle. Each hamster is represented by a different color. 5-HT and melatonin secretion from the same hamster is shown in the same color. B. Comparison of 5-HT (upper panel) and melatonin (lower panel) secretion profiles from outbred animals. Data from SD rats (red), Wistar rats (green), and hamsters (blue) are superimposed to show the relative timing of 5-HT and melatonin secretion.

Figure 5
Comparison of the relative timing of 5-HT onset (5HT-on) and melatonin onset (MT-on). SD: red dots (n = 6), PVG: blue dots (n = 4), LEW: yellow dots (n = 4), Wistar: green dots (n = 8), Syrian hamsters: blue dots (n = 3). The 5HT-on represents the intervals (min) between the dark onset (18:00 h in all animals) and the early 5-HT surge at 80% of the nocturnal maximum levels. The MT-on indicates the time interval (min) between the dark onset (18:00 h) and the melatonin onset at 20% of the nocturnal maximum levels. The vertical dashed line represents the 5HT-on at 60 min, whereas the horizontal dashed lines represent values of MT-on from hamsters (upper line, 300 min) and rats (lower line, 110 min) when 5HT-on is 60 min.
