Developmental alterations in 5-hydroxytryptamine concentration and turnover after treatment of neonatal rats with...

Early disruption of the serotonin neurotransmitter system may have important consequences for normal neuro-physiological development. In order to further understand the neurochemical changes which occur after early insults to the system, intracerebroventricular injections of the serotonin-selective toxin, 5,7-dihydroxytryptamine were given to Sprague-Dawley rat pups on day 3 of life. Serotonin and 5-hydroxyindoleacetic acid concentration in cortex, striatum, hippocampus, and brainstem were measured after 4, 8, and 12 weeks. In controls, serotonin concentration in the striatum and cortex increased from 4 to 12 weeks, while it reached adult levels by 4 weeks in the hippocampus. 5-Hydroxyindoleacetic acid increased in cortex and hippocampus and was unchanged after 4 weeks in the striatum. An index of serotonin turnover (5-hydroxyindoleacetic acid/serotonin) decreased in striatum and cortex, but increased in the hippocampus over time. 5,7-Dihydroxytryptamine treatment induced permanent decreases in serotonin and 5-hydroxyindoleacetic acid concentration in all three forebrain regions, but had no region- and time-specific effects on serotonin turnover. In the brainstem of controls, serotonin concentration increased from 4 to 12 weeks, while 5-hydroxyindoleacetic acid concentration was unchanged, resulting in decreasing turnover. After 5,7-dihydroxytryptamine treatment, the brainstem did not show depletions of serotonin concentration in spite of significant serotonin neuronal loss, suggesting that compensatory mechanisms in remaining neurons may permit increased serotonin production. Regional and time-dependent responses to serotonin depletion may have functional implications for the developmental regulation of serotonin transmission after early insults to this neurotransmitter system.