Endogenous regulation of serotonin release in the hamster suprachiasmatic nucleus.
Serotonin (5-HT) has been strongly implicated in the regulation of the mammalian circadian clock located in the suprachiasmatic nuclei (SCN). However, little is known of the pattern of neuronal 5-HT release in the SCN or of the factors involved in regulating its release. Using in vivo microdialysis, we demonstrated the existence of a daily rhythm in the output of 5-HT in the SCN of freely behaving hamsters. This rhythm was characterized by a sharp increase in release from a nadir during late midday to peak levels at the light/dark transition. Output declined to basal levels throughout the remainder of the night. A similar pattern also was evident under constant darkness, with increased 5-HT output occurring at the onset of subjective night. Locomotor activity induced by exposure to a novel running wheel had a pronounced phase-dependent effect on 5-HT release in the SCN, with stimulation during the light phase and suppression during the late dark phase. Systemic application of the somatodendritic 5-HT1A agonist BMY 7378 had a significantly greater suppressive effect on 5-HT release in the SCN during the late dark phase compared with mid light phase, indicating that a variation in raphe autoreceptor response may underlie the time-dependent effects of wheel running on 5-HT release. Collectively, these results show that the daily rhythm in output of 5-HT in the SCN is generated endogenously, and that behavioral state can strongly influence serotonergic activity in the circadian clock in a phase-dependent manner.
Dudley
T E
TE
Department of Biological Sciences, Kent State University, Kent, Ohio 44242-0001, USA.
DiNardo
L A
LA
Glass
J D
JD
D000818:Animals; D017660:Autoreceptors / Q000819:agonists; D002940:Circadian Rhythm / Q000502:physiology*; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D017551:Microdialysis; D009043:Motor Activity / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D017660:Autoreceptors; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; C053428:BMY 7378