Changes in monoamine metabolites concentrations in rat cerebrospinal fluidafter acute and long-term administration of a selective serotonin reuptakeinhibitor, trazodone

In order to clarify the mechanism of the antidepressive effects of trazodon e, a selective serotonin reuptake inhibitor, we investigated the dynamics o f monoamine metabolites in cerebrospinal fluid (CSF) of free-moving conscio us rats by acute and long-term treatment with trazodone. When 100 mg kg(-1) p.o. of trazodone were administered, a significant increase of 3-methoxy-4 -hydroxyphenylglycol (MHPG) concentration was soon observed in the light pe riod of the light/dark cycle, and a significant decrease of dihydroxy pheny l acetic acid (DOPAC) concentration was observed during the 2 days after ad ministration of trazodone; in contrast, the homovanilic acid (HVA) level wa s increased. However, we detected no significant changes in the 5-hydroxy i ndole-3-acetic acid (5-HIAA) concentration during the 3 days. In the case o f long-term treatment with 50 mg kg-l, p.o. of trazodone, the levels of MHP G, DOPAC and HVA exhibited no difference when compared with values obtained during saline treatment in either the light or dark period, whereas the le vels of 5-HIAA showed a significant increase during the light period. These findings suggest that a long-term treatment with trazodone enhances the se rotonergic neurons. (C) 1999 Academic Press.