The Journal of Neuroscience, July 15, 2001, 21(14):5351-5357
In Vivo Resetting of the Hamster Circadian Clock
by 5-HT7 Receptors in the Suprachiasmatic
Nucleus
J. Christopher
Ehlen,
Gregory
H.
Grossman, and
J. David
Glass
Department of Biological Sciences, Kent State University, Kent,
Ohio 44242
Serotonin (5-HT) has been strongly implicated in the regulation of
the mammalian circadian clock located in the suprachiasmatic nuclei
(SCN); however, its role in behavioral (nonphotic) circadian phase
resetting remains elusive. Central to this issue are divergent lines of
evidence that the SCN may, or may not, be a target for the
phase-resetting effects of 5-HT. We have addressed this question using
a novel reverse-microdialysis approach for timed perfusions of
serotonergic and other agents to the Syrian hamster SCN with durations
equivalent to the increases in in vivo 5-HT release during phase-resetting behavioral manipulations. We found that 3 hr
perfusions of the SCN with either 5-HT or the 5-HT1A,7
receptor agonist
2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydro-naphthalene (8-OH-DPAT) at midday advanced the phase of the free-running
circadian rhythm of wheel-running assessed using an Aschoff type II
procedure. Phase shifts induced by 8-OH-DPAT were enhanced more than
threefold by pretreatment with the 5-HT synthesis inhibitor
para-chlorophenylalanine. Phase advances induced by SCN
8-OH-DPAT perfusion were significantly inhibited by the
5-HT2,7 receptor antagonist ritanserin and by the more
selective 5-HT7 receptor antagonist DR4004, implicating the
5-HT7 receptor in mediating this phase resetting.
Concurrent exposure to light during the 8-OH-DPAT perfusion abolished
the phase advances. Furthermore, coperfusion of the SCN with TTX, which
blocked in vivo 5-HT release, did not suppress intra-SCN 8-OH-DPAT-induced phase advances. These results indicate that 5-HT7 receptor-mediated phase resetting in the SCN is
markedly influenced by the degree of postsynaptic responsiveness to
5-HT and by photic stimulation. Finally, 5-HT may act directly on SCN clock cells to induce in vivo nonphotic phase resetting.
Key words:
suprachiasmatic nucleus; serotonin; 8-OH-DPAT; DR4004; ritanserin; circadian rhythm; hamster; in vivo brain
microdialysis; phase-resetting; behavioral rhythm
Copyright © 2001 Society for Neuroscience 0270-6474/01/21145351-07$05.00/0
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