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Serotonin and the Mammalian Circadian System: I. In Vitro Phase Shifts by Serotonergic Agonists and Antagonists
Rebecca A. Prosser
Department of Biological Sciences, Stanford University
Robin R. Dean
Sleep Research Center, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305
Dale M. Edgar
Sleep Research Center, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305
H. Craig Heller
Department of Biological Sciences, Stanford University
Joseph D. Miller
Department of Biological Sciences, Stanford University, Sleep Research Center, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305
The primary mammalian circadian clock, located in the suprachiasmatic nuclei (SCN), receives a major input from the raphe nuclei. The role of this input is largely unknown, and is the focus of this research. The SCN clock survives in vitro, where it produces a 24-hr rhythm in spontaneous neuronal activity that is sustained for at least three cycles. The sensitivity of the SCN clock to drugs can therefore be tested in vitro by determining whether various compounds alter the phase of this rhythm. We have previously shown that the nonspecific serotonin (5-HT) agonist quipazine resets the SCN clock in vitro, inducing phase advances in the daytime and phase delays at night. These results suggest that the 5-HT-ergic input from the raphe nuclei can modulate the phase of the SCN circadian clock. In this study we began by using autoradiography to determine that the SCN contain abundant 5-HT 1A and 5-HT1B receptors, very few 5-HT1C and 5-HT 2 receptors, and no 5-HT3 receptors. Next we investigated the ability of 5-HT-ergic agonists and antagonists to reset the clock in vitro, in order to determine what type or types of 5-HT receptor(s) are functionally linked to the SCN clock. We began by providing further evidence of 5-HT-ergic effects in the SCN. We found that 5-HT mimicked the effects of quipazine, whereas the nonspecific 5-HT antagonist metergoline blocked these effects, in both the day and night. Next we found that the 5-HT1A agonist 8-OH-DPAT, and to a lesser extent the 5-HT1A-1B agonist RU 24969, mimicked the effects of quipazine during the subjective daytime, whereas the 5-HT 1A antagonist NAN-190 blocked quipazine's effects. None of the other specific agonists or antagonists we tried induced similar effects. This suggests that quipazine acts on 5-HT1A receptors in the daytime to advance the SCN clock. None of the specific agents we tried were able either to mimic or to block the actions of 5-HT or quipazine at circadian time 15. Thus, we were unable to determine the type of 5-HT receptor involved in nighttime phase delays by quipazine or 5-HT. However, since the dose-response curves for quipazine during the day and night are virtually identical, we hypothesize that the nighttime 5-HT receptor is a 5-HT1-like receptor.
Key Words: circadian rhythms • suprachiasmatic nucleus • serotonin • 5-HT1A receptors • oscillator • brain slices
Journal of Biological Rhythms, Vol. 8, No. 1,
1-16 (1993)
DOI: 10.1177/074873049300800101
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|
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|
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|
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|
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|
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|
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|
|
|
|
|
|
|
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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16(1):
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[Abstract]
[PDF]
|
|
|
|
|
|
|
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[PDF]
|
|
|
|
|
|
|
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October 1, 1999;
14(5):
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[Abstract]
[PDF]
|
|
|
|
|
|
|
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August 1, 1999;
82(2):
533 - 539.
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|
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[Full Text]
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|
|
|
|
|
|
|
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81(4):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
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14(2):
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[Abstract]
[PDF]
|
|
|
|
|
|
|
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J Biol Rhythms,
December 1, 1998;
13(6):
494 - 505.
[Abstract]
[PDF]
|
|
|
|
|
|
|
E. Challet, K. Scarbrough, P. D. Penev, and F. W. Turek
Roles of Suprachiasmatic Nuclei and Intergeniculate Leaflets in Mediating the Phase-Shifting Effects of a Serotonergic Agonist and Their Photic Modulation during Subjective Day
J Biol Rhythms,
October 1, 1998;
13(5):
410 - 421.
[Abstract]
[PDF]
|
|
|
|
|
|
|
W. C. Duncan Jr., K. A. Johnson, and T. A. Wehr
Decreased Sensitivity to Light of the Photic Entrainment Pathway during Chronic Clorgyline and Lithium Treatments
J Biol Rhythms,
August 1, 1998;
13(4):
330 - 346.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. E. Dudley, L. A. DiNardo, and J. D. Glass
Endogenous Regulation of Serotonin Release in the Hamster Suprachiasmatic Nucleus
J. Neurosci.,
July 1, 1998;
18(13):
5045 - 5052.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. K. Gribkoff, R. L. Pieschl, T. A. Wisialowski, A. N. van den Pol, and F. D. Yocca
Phase Shifting of Circadian Rhythms and Depression of Neuronal Activity in the Rat Suprachiasmatic Nucleus by Neuropeptide Y: Mediation by Different Receptor Subtypes
J. Neurosci.,
April 15, 1998;
18(8):
3014 - 3022.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Prosser
In Vitro Circadian Rhythms of the Mammalian Suprachiasmatic Nuclei: Comparison of Multi-Unit and Single-Unit Neuronal Activity Recordings
J Biol Rhythms,
February 1, 1998;
13(1):
30 - 38.
[Abstract]
[PDF]
|
|
|
|
|
|
|
E. Challet, P. Pevet, and A. Malan
Lesion of the Serotonergic Terminals in the Suprachiasmatic Nuclei Limits the Phase Advance of Body Temperature Rhythm in Food-Restricted Rats Fed during Daytime
J Biol Rhythms,
June 1, 1997;
12(3):
235 - 244.
[Abstract]
[PDF]
|
|
|
|
|
|
|
G. E. Pickard, E. T. Weber, P. A. Scott, A. F. Riberdy, and M. A. Rea
5HT1B Receptor Agonists Inhibit Light-Induced Phase Shifts of Behavioral Circadian Rhythms and Expression of the Immediate-Early Gene c-fos in the Suprachiasmatic Nucleus
J. Neurosci.,
December 15, 1996;
16(24):
8208 - 8220.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.D. Glass, M. Selim, G. Srkalovic, and M.A. Rea
Tryptophan Loading Modulates Light-Induced Responses in the Mammalian Circadian System
J Biol Rhythms,
March 1, 1995;
10(1):
80 - 90.
[Abstract]
[PDF]
|
|
|
|
|
