Serotonergic potentiation of dark pulse-induced phase-shifting effects at midday in hamsters.
In mammals, resetting of the suprachiasmatic clock (SCN) by behavioral activation or serotonin (5-HT) agonists is mimicked by dark pulses, presented during subjective day in constant light (LL). Because behavioral resetting may be mediated in part by 5-HT inputs to the SCN, here we determined whether 5-HT system can modulate dark-induced phase-shifts in Syrian hamsters housed in LL. Two hours of darkness at mid-subjective day (circadian time 6; CT-6) resulted in increased concentrations of 5-HT in the SCN tissue and induction of c-FOS expression in the raphe nuclei. Injections of the 5-HT(1A/7) agonist +8-OH-DPAT or dark pulses at CT-6 induced phase-advances of the wheel-running activity rhythm and down-regulated the expression of the clock genes Per1-2 and c-FOS in the SCN in a similar way. The combination of both treatments [+8-OH-DPAT + dark pulses], however, resulted in larger phase-advances, while associated molecular changes were not significantly modified, except for the gene Dbp, in comparison to +8-OH-DPAT or dark pulses alone. Dark resetting was blocked by pre-treatment with a 5-HT(7) antagonist, but not with a 5-HT(1A) antagonist. The additive phase-shifts of two different cues to reset the SCN clock open wide the gateway for non-photic shifting, leading to new strategies in chronotherapy.
Mendoza
Jorge
J
Institut de Neurosciences Cellulaires et Intégratives, Département de Neurobiologie des Rythmes, CNRS et Université Louis Pasteur, Strasbourg, France. jmendoza@neurochem.u-strasbg.fr
Clesse
Daniel
D
Pévet
Paul
P
Challet
Etienne
E
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D003624:Darkness; D008297:Male; D008647:Mesocricetus; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010775:Photic Stimulation; D011897:Random Allocation; D012701:Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology
D017366:Serotonin Receptor Agonists; D012701:Serotonin