Persistently increased density of serotonin transporters in the frontal cortex of rats treated with fluoxetine during early juvenile life

This experimental animal study was performed in order to assess possible lo ng-term effects of the administration of the selective serotonin reuptake i nhibitor fluoxetine (Prozac(R)) during early periods of juvenile life on th e developing central serotonergic and noradrenergic systems. Fluoxetine was administered via the drinking water (5 mg/kg/day) for a period of two week s to very young (day 25) and somewhat older (day 50) rats. The effect of th is treatment on the density of serotonin and noradrenaline transporters was measured by ligand-binding assays in various brain regions. The B-max-valu es of [H-3]-nisoxetine binding were not affected by either treatment schedu le, but a significant increase of the B-max-values of ra]-paroxetine bindin g was found in the brains of early fluoxetine-treated rats. This increase w as restricted to the frontal cortex and persisted long after the terminatio n of the treatment into adulthood (day 90), The most likely explanation of this observation is a stimulatory effect of the fluoxetine treatment on the outgrowth of serotonergic projections in the frontal cortex of very young rats. This is the first empirical demonstration of long-lasting effects of the administration of a selective serotonin reuptake inhibitor during juven ile life on the maturation of the central serotonergic system.