DEVELOPMENTAL ALTERATIONS IN 5-HYDROXYTRYPTAMINE CONCENTRATION AND TURNOVER AFTER TREATMENT OF NEONATAL RATS WITH 5,7-DIHYDROXYTRYPTAMINE

Early disruption of the serotonin neurotransmitter system may have imp ortant consequences for normal neurophysiological development. In orde r to further understand the neurochemical changes which occur after ea rly insults to this system, intracerebroventricular injections of the serotonin-selective toxin, 5,7-dihydroxytryptamine were given to Sprag ue-Dawley rat pups on Day 3 of life. Serotonin and 5-hydroxyindoleacet ic acid concentration in cortex, striatum, hippocampus, and brainstem were measured after 4, 8, and 12 weeks. In controls, serotonin concent ration in the striatum and cortex increased from 4 to 12 weeks, while it reached adult levels by 4 weeks in the hippocampus. 5-Hydroxyindole acetic acid increased in cortex and hippocampus and was unchanged afte r 4 weeks in the striatum. An index of serotonin turnover (5-hydroxyin doleacetic acid/serotonin) decreased in striatum and cortex, but incre ased in the hippocampus over time. 5,7-Dihydroxytryptamine treatment i nduced permanent decreases in serotonin and 5-hydroxyindoleacetic acid concentration in all three forebrain regions, but had region- and tim e-specific effects on serotonin turnover. In the brainstem of controls , serotonin concentration increased from 4 to 12 weeks, while 5-hydrox yindoleacetic acid concentration was unchanged, resulting in decreasin g turnover. After 5,7-dihydroxytryptamine treatment, the brainstem did not show depletions of serotonin concentration in spite of significan t 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 functiona l implications for the developmental regulation of serotonin transmiss ion after early insults to this neurotransmitter system. (C) 1996 Acad emic Press, Inc.