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Abstract— Although the serotoninergic innervation is immature in the brains of young rats, the 5‐HIAA content is similar to that found in adults. As indicated by the ratio of 5‐HIAA to 5‐HT levels in the brain stem and the forebrain, the catabolism of the indolamine was more rapid during the first 3 postnatal weeks than in adults. This was contirmed by measuring the total formation of [3H]5‐HIAA from [3H]5‐HT newly synthesized from L‐[3H]tryptophan in brain stem slices of young and adult rats. Electrolytic lesions of midbrain raphe nuclei (B7 and B8) performed on the 5th postnatal day resulted in parallel decreases in brain 5‐HT and 5‐HIAA levels; this ruled out the possibility that 5‐HIAA might be formed from 5‐HT synthesized outside serotoninergic neurons, using peripheral 5‐hydroxytryptophan. Inhibition of 5‐HT storage by reserpine pretreatment did not alter the higher capacity of newborn tissues to catabolize exogenous [3H]5‐HT. Therefore, possible differences in 5‐HT binding in serotoninergic neurons between newborn and adult rats were not likely to account for the differences in 5‐HT catabolism. Estimation of the rate of 5‐HIAA efflux from the brain after MAO inhibition did not reveal marked changes with age. The activity of MAO type A, the enzyme involved in 5‐HT catabolism, was higher during early life than later on. This could be shown by using 5‐HT as substrate and clorgyline as a selective inhibitor. An opposite pattern of development was seen for MAO B, measured with benzylamine as substrate and deprenyl as selective inhibitor. These results suggest that the high 5‐HIAA levels found in the brains of young rats can be attributed mainly to the presence of high MAO A activity during early life.

Abstract:The raphe-hippocampal serotonin (5-HT) system is involved in the regulation of the hypothalamuspituitary-adrenal axis. The purpose of this study was to determine and compare the roles of 5-HT in the regulation of glucocorticoid receptor (GR) binding in the raphe nuclei and in the hippocampus. The effects of 5-HT, 5-HT agonists, and the 5-HT reuptake inhibitor citalopram on GR binding sites were studied in primary cultures of the fetal raphe nuclei and the hippocampus. . These results show that the regulation of GRs during fetal life is structure-dependent and involves different 5-HT receptor subtypes. Moreover, the regulation of hippocampal GRs by citalopram suggests an action of antidepressants independent of their effects on monoamines.

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