5‐hydroxytryptamine Catabolism in the Rat Brain During Ontogenesis

Abstract

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.

Developmental Variations of Brain Serotonin, Tryptophan, 5-Hydroxyindole Acetic Acid, and Noradrenaline and Dopamine Content in Two Inbred Strains of Mice

“…As previously demon strated for other species [3,6,12] at birth, high 5-HIAA levels have also been observed in the brainstem, most probably due to high 5-HT-specific MAO A activity as recently demonstrated by Bourgoin et al [6] in the newborn rat. The increase of 5-HT level dur ing postnatal life is more marked and more gradual in the forebrain than in the brain stem.…”

Postnatal development of dopaminergic neurons in the rabbit retina

“…This correlation was later substantiated by a similar study in the rat brain. Bourgoin et al (1977) demonstrated that, in the rat brain, the MAO-A activity was higher during early life than in the adult. On the contrary, the MAO-B activity increased steadily from newborn to the adult brain.…”

“…The specific activity of this enzyme in the adult rabbit retina was found to be 4.5 + 0.8 pmol of dopamine degraded/gm of protein/hr. Since two distinct types of MAO, MAO-A and MAO-B, are known to exist in different tissues (Hall et al, 1969;Roth and Gillis, 1975) and follow different developmental patterns (Bourgoin et al, 1977;McCaman and Aprison, 1964), the characteristics of MAO in the rabbit retina were further examined pharmacologically by using specific inhibitors Vol. 1, No.…”

Maternal Influences on Tryptophan Hydroxylase Activity in Embryonic Rat Brain

“…Moreover, since MAO activity is high in the immature brain [3,5,6,16,23], this inhibition of TPH activity could lead to a large-scale depletion of 5-HT in the embryo. Such a deficit, occurring between 8 and 17 days of gestation, at a time when 5-HT may be re quired as a developmental signal, might ac count for our previous observation of altered neuronal genesis in the embryonic brain as a consequence of maternal pCPA treatment [20, 21], The increased activity of embryonic TPH as a result of maternal tryptophan injections Values are means rfcSEM.…”