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 long-term effects of the administration of the selective serotonin reuptake inhibitor fluoxetine (Prozac) during early periods of juvenile life on the developing central serotonergic and noradrenergic systems. Fluoxetine was administered via the drinking water (5 mg/kg/day) for a period of two weeks to very young (day 25) and somewhat older (day 50) rats. The effect of this treatment on the density of serotonin and noradrenaline transporters was measured by ligand-binding assays in various brain regions. The Bmax-values of [3H]-nisoxetine binding were not affected by either treatment schedule, but a significant increase of the Bmax-values of [3H]-paroxetine binding was found in the brains of early fluoxetine-treated rats. This increase was restricted to the frontal cortex and persisted long after the termination 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 juvenile life on the maturation of the central serotonergic system.