Effects of Neonatal 5,7-Dihydroxytryptamine Treatment on the Development of Serotonin Neurons and Their Transmitter Metabolism

Abstract

The effects of neonatal treatment of rats, systemically, with the neurotoxin 5,7-di-hydroxytryptamine (5,7-HT) on the central 5-hydroxytryptamine (5-HT) neurons as monitored by neurochemical analysis have been investigated. In agreement with previous studies this treatment caused a marked and permanent reduction in endogenous 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and 3H-5-HT uptake in distant 5-HT nerve terminal projections, cerebral cortex and spinal cord, while these parameters were considerably increased in the mesencephalon-pons-medulla, the 5-HT cell body-containing regions. These changes reflect a marked 5-HT denervation in distant nerve terminal projections and a hyperinnervation in cell body-near regions. The neurotoxic effects of 5,7-HT on central noradrenaline neurons could be counteracted completely by pretreatment with the uptake blocker desipramine. No neurotoxic effects were noted on dopamine neurons. Despite the marked regional changes in 3H-5-HT uptake caused by 5,7-HT, only a minor reduction was observed when analyzing the uptake in the whole central nervous system. Sectioning of ascending 5-HT axons in the mesencephalon of 2-day-old rats led to similar regional changes in 3H-5-HT uptake as those seen after 5,7-HT treatment. These results strongly support the contention that the altered development of central 5-HT neurons caused by 5,7-HT is due to a ''pruning effect''. The changes in 5-HT levels, in both directions, were in all regions and groups studied consistently more pronounced than the corresponding alterations of 5-HIAA levels, suggesting an increased transmitter turnover in remaining 5-HT nerve terminals of denervated regions, whereas the reverse seems to be the case in the hyperinnervated areas. These changes may represent compensatory mechanisms in response to the altered development of the 5-HT neurons after 5,7-HT.