Effects of para-chloroamphetamine upon the serotonergic innervation of the rat hippocampus.
The ability of hippocampal serotonergic (5-HT) axons to proliferate in response to damage by para-chloroamphetamine (PCA) was examined in this study. Synaptosomal uptake of 5-HT in the hippocampal formation was decreased to 40% of control 3 days after systemic administration of PCA. Six weeks after PCA, uptake values were 44% of control. Retrograde tracing combined with 5-HT immunocytochemistry showed a significant reduction (18% of control) in the number of 5-HT raphe neurons projecting to the hippocampus 3 days after PCA. The number of 5-HT neurons projecting to the hippocampal formation increased to 69% of control by 6 weeks. The dorsal raphe nucleus was not retrogradely labeled after PCA; the increase in labeled neurons was observed in the median raphe nucleus. PHA-L, injections of the median raphe nucleus demonstrated a reduction of raphe axons in the hippocampal formation after PCA. In rats treated with PCA, raphe axons labeled with PHA-L also appeared to have fewer boutons than raphe axons labeled in control cases. The density of PHA-L containing axons in the hippocampal formation of rats injected 3 days and 6 weeks after PCA was less than control but there was no difference between the experimental groups. Based upon the results from synaptosomal uptake and anterograde tracing experiments, we feel that compensatory proliferation of 5-HT axons does not occur within 6 weeks of PCA-induced damage to the 5-HT plexus of the hippocampal formation. The data derived from the retrograde tracing experiment are thought to reflect reduced uptake and transport of WGA-HRP as an acute effect of PCA.