PHARMACOKINETICS OF EXTRACELLULAR MELATONIN IN SIBERIAN HAMSTER FOREBRAIN

In vivo brain microdialysis was used to characterize the pharmacokinet ics of subcutaneously injected melatonin in the anterior hypothalamic- preoptic area (AH-POA) of the male Siberian hamster. Animals with a mi crodialysis probe implanted in the AH-POA were treated with a subcutan eous melatonin injection at 0900 h (3 h after lights-on) or 2000 h (2 h prior to lights-off). Treatment with 2.5 or 0.25 mg/kg dosages of me latonin in saline vehicle induced peak concentrations of melatonin in AH-POA microdialysates within 20 min of injection (165 +/- 34 and 18 /- 8 pg/20 min, respectively). For the 2.5 and 0.25 mg/kg dosages, the half-life of the absorbed melatonin (t(1/2) elimination) was less tha n 20 min, and the concentrations fell to baseline within 60 min after injection. There were no significant time of day effects on the kineti c profile of extracellular melatonin associated with either of these d osages. These results confirm the rapid accumulation and clearance of extracellular melatonin in the vicinity of its putative target tissues .