Very early treatment with fluoxetine and reboxetine causing long-lasting change of the serotonin but not the noradrenaline transporter in the frontal cortex of rats

Interactions of the serotonergic and noradrenergic system at different sites of the brain may be important for efficacy and side effects of antidepressant drugs. Further, serotonin and noradrenaline play a critical role in the development of neurons during brain maturation. To gain further insight how brain maturation and the two monoaminergic systems are influenced by drug treatment during early postnatal development, this animal study investigated possible effects on the noradrenaline and serotonin transporter density of the frontal cortex very early in postnatal life. Rats were treated from postnatal day 2 to 5 either with fluoxetine (5 mg/kg per day s.c.) or with reboxetine (10 mg/kg per day s.c.). At day 90 the serotonin and noradrenaline transporter density in the frontal cortex was measured by ligand binding assay. Fluoxetine treatment led to a significant long-lasting increase of serotonin (not noradrenaline) transporter density (B-max = 1231 +/- 34) in the frontal cortex (compared with saline-treated controls (B-max = 1112 +/- 58)). Reboxetine treatment (surprisingly) led to an even more enhanced serotonin transporter density (B-max =1322 +/- 46), while noradrenaline transporter density seemed to be unaffected. There were no significant differences for K-D values. The results support the idea that serotonin seems to play an important role during early brain development. Moreover, drug-related modulation of the noradrenergic system during brain maturation seems to cross-influence the serotonergic system.