ENTRAINMENT OF CIRCADIAN-RHYTHMS BY S-20098, A MELATONIN AGONIST, IS DOSE AND PLASMA-CONCENTRATION DEPENDENT

The present study determined first the dose-response (0.5 to 10 mg . k g(-1)) to daily oral administration of S-20098. a melatonin agonist, i n entraining circadian rhythms of rats free-running in constant darkne ss; second, the relation between entrainment and the plasma concentrat ion of S-20098. Finally, responses to 8 mg . kg(-1) of S-20098 were co mpared with those obtained with the same dose of melatonin and ipsapir one. Responses were classified as negative, transient, or true entrain ment. The data indicated a clear dose-dependent response from 2.5 to 1 0 mg . kg(-1) of S-20098 with an EDS, of 5.7 mg . kg(-1) for true entr ainment and a clear relation between entrainment and the plasma concen tration of S-20098. S-20098 was as effective as melatonin to entrain f ree-running rhythms. Ipsapirone was ineffective in our experimental co nditions.