US EPA

1493595 

Journal Article 

In vivo resetting of the hamster circadian clock by 5-HT7 receptors in the suprachiasmatic nucleus 

Ehlen, JC; Grossman, GH; Glass, JD 

2001 

Yes 

Journal of Neuroscience
ISSN: 0270-6474
EISSN: 1529-2401 

21 

14 

5351-5357 

11438611 

WOS:000169692800045 

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. 

suprachiasmatic nucleus; serotonin; 8-OH-DPAT; DR4004; ritanserin; circadian rhythm; hamster; in vivo brain microdialysis; phase-resetting; behavioral rhythm