Transient reduction in hippocampal serotonergic innervation after neonatal parachloroamphetamine treatment.

This study examined the effects of parachloroamphetamine on neonatal forebrain serotonergic (5-HT) innervation. Rat pups were treated with PCA on P3 and P4. Significant reductions in 5-HT content were observed in the hippocampal formation, frontal cortex and entorhinal cortex on P5 and P7. By P14, neocortical 5-HT had returned to normal levels while hippocampal 5-HT values remained less than control. Hippocampal 5-HT content reached normal range by P21. High affinity 5-HT uptake in hippocampal synaptosomal preparations was similarly reduced on P5 and P7 suggesting that 5-HT terminals were being lesioned by PCA. 5-HT uptake recovered significantly by P14 perhaps reflecting the extraordinary plasticity of the 5-HT projections in the neonate. However, in contrast to the complete restoration of hippocampal 5-HT content, 5-HT uptake values remained significantly less than control. No change in 5-HT content was observed in either the hypothalamus or midbrain raphe at any age studied. Thus, the rapid onset of effects, regional selectivity and transient reduction of 5-HT levels recommend the use of PCA in studies of the role of 5-HT in hippocampal development.