Serotonergic activation potentiates light resetting of the main circadian clock and alters clock gene expression in a diurnal rodent.
The main circadian clock, localized in the suprachiasmatic nuclei (SCN) in mammals, can be synchronized by light and non-photic factors such as serotonergic cues. In nocturnal rodents, injections during the subjective day of the 5-HT1A/7 receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) or its positive enantiomer, induce behavioral phase-advances in correlation with decreased expression of two clock genes, Per1/2. In addition, 8-OH-DPAT and the selective serotonin reuptake inhibitor fluoxetine reduce light-induced phase-shifts during the subjective night. Beside the chronobiotic effects of serotonin, changes of serotonergic activity in humans have been involved in mood disorders, that are often associated with alterations in circadian rhythmicity. To get insights into the circadian role of serotonin in diurnal species, we investigated its modulation of the SCN in Arvicanthis ansorgei housed in constant darkness. In striking contrast to nocturnal rodents, daily serotonin content in Arvicanthis SCN peaked during daytime while the sensitivity window of its SCN to (+)8-OH-DPAT occurred essentially during the subjective night. Moreover, fluoxetine produced behavioral phase-advances at circadian time (CT) 0 and CT12. Expression of Per1/2, Rev-erbalpha/beta and Roralpha/beta in the SCN was not modified after fluoxetine or (+)8-OH-DPAT injection. Furthermore, both treatments enhanced light-induced phase-advances and delays. Light responses of Per1 and Rorbeta expression at CT0 and those of Per2 and Rev-erbalpha at CT12 were markedly altered by serotonergic activation. The present findings demonstrate that the serotonergic modulation of the SCN clock appears to differ between nocturnal species and the diurnal Arvicanthis. The potentiating effects of fluoxetine on light resetting in a diurnal rodent may be clinically relevant.
Cuesta
Marc
M
Département de Neurobiologie des Rythmes, Institut de Neurosciences Cellulaires et Intégratives, UMR7168, CNRS, Université Louis Pasteur, 5 rue Blaise Pascal, 67084 Strasbourg cedex, France.
Mendoza
Jorge
J
Clesse
Daniel
D
Pévet
Paul
P
Challet
Etienne
E
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008027:Light; D008297:Male; D056950:Period Circadian Proteins; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018797:Cell Cycle Proteins; D005473:Fluoxetine; D006897:Hydroxyindoleacetic Acid; D056950:Period Circadian Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C539022:PER1 protein, human; C539024:Per1 protein, rat