Comparative effects of a melatonin agonist on the circadian system in mice and Syrian hamsters.
S-20098 has potent and specific agonist properties on melatonin receptors both in vitro and in vivo. Behavioral studies on rodents already showed that repeated intraperitoneal administration of S-20098 could dose-dependently alter the functioning of the circadian clock. To determine whether single administration of S-20098 could alter the circadian rhythms of rodents, we first used the phase-response curve (PRC) approach in two different species: Syrian hamsters and mice (C3H/HeJ). Our results show that the shape, circadian times and extent of the PRC to S-20098 look very similar in mice and hamsters. In both species, the phase advance portion of the PRC to S-20098 is limited to a 3 h window preceding the onset of locomotor activity, but the magnitude of phase shifts is larger in mice. We also tested the phase shifting effects of increasing doses of S-20098 during the interval of maximal sensitivity to this compound. Treatment with S-20098 induces dose-dependent phase shifts, with maximal shifts observed after injections of 20 and 25 mg/kg S-20098 i.p., respectively, in mice and hamsters. Those results are in agreement with the limited distribution of melatonin-binding sites within the circadian clock of adult Syrian hamsters, as compared to other rodents.
Van Reeth
O
O
Centre des Rythmes Biologiques, School of Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. ovanree@resulb.ulb.ac.be
Olivares
E
E
Zhang
Y
Y
Zee
P C
PC
Mocaer
E
E
Defrance
R
R
Turek
F W
FW
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D008550:Melatonin / Q000819:agonists*; D008647:Mesocricetus / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H / Q000502:physiology*; D013045:Species Specificity; D009281:Naphthalenes
D000081:Acetamides; D006993:Hypnotics and Sedatives; D008550:Melatonin; C084711:agomelatine; D009281:Naphthalenes