Effects of postnatal isolation rearing and antidepressant treatment on the density of serotonergic and noradrenergic axons and depressive behavior in rats.

The development of monoaminergic axons is affected by pharmacological and environmental manipulations during early periods of brain development. In addition, it has been proposed that changes in the density of monoaminergic axons are involved in the pathophysiology of depression. The present experiments examined the effects of neonatal treatment with antidepressants on the density of monoaminergic axons containing 5-HT or noradrenaline (NA) and depressive behavior in rats. In this study, clomipramine (CL) was used as an antidepressant, because a large amount of data has been accumulated on the effects of neonatal CL treatment on monoaminergic neurons and depressive behavior. It was also examined whether the effects of neonatal CL treatment could be further modified by environmental conditions. In the present experiments, postweaning isolation rearing (Iso) was examined as an environmental condition, because postweaning Iso is reported to change the density of 5-HT axons in the rat brain. Unexpectedly, neonatal CL treatment alone had no effect on the density of 5-HT or NA axons or depressive behavior. Postweaning social Iso rearing reduced the density of 5-HT axons in the central nucleus and basolateral nucleus of the amygdala and CA3 of the hippocampus. In the prelimbic area and infralimbic area of medial prefrontal cortex and the dentate gyrus of the hippocampus, the density of 5-HT axons was not affected by social Iso alone, but was reduced when animals were socially isolated after neonatal CL treatment. Postweaning Iso, but not neonatal CL treatment, increased immobility in the forced swim test in adolescence/early adulthood. These findings suggest that postweaning social Iso alters the density of monoaminergic axons, particularly 5-HT axons, and induces a possible model of depression, while neonatal CL treatment alone has no effect on the density of NA or 5-HT axons or depressive behavior in adolescence/early adulthood.