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Bourgoin S, Artaud F, Enjalbert A, Héry F, Glowinski J, Hamon M. 
“Acute Changes In Central Serotonin Metabolism Induced By The Blockade Or Stimulation Of Serotoninergic Receptors During Ontogenesis In The Rat”. 
J. Pharmacol. exp. Ther.. 1977;202(3):519-631.
Both the synthesis and utilization of serotonin (5-HT) are accelerated in the brain of the adult rat after the administration of the 5-HT antagonist methiothepin. In contrast, the reverse observed when the central 5-HT agonist, LSD, is administered. The present study was undertaken in order to determine if these metabolic events also occur in the newborn rat. Serotoninergic receptors are linked to an adenylate cyclase in the brain of the newborn rat. The effects of methiothepin and LSD on this enzyme demonstrated that methiothepin and LSD could be also considered, respectively, as an antagonist and a partial agonist of 5-HT in the central nervous system of the neonate. The administration of methiothepin induced an acceleration in the rate of synthesis in the brain of newborn rats as it does in adult animals. In contrast, LSD treatment resulted in a partial inhibition of 5-HT synthesis only in rats older than 8 days of age. These results were confirmed by estimating the rate of 5-HT synthesis in vitro in brain slices prepared from rats treated with methiothepin or LSD. The addition of 30 mM Ki to the incubating medium of brain stem slices from adult or young rats (12 hours and 7 days oldj induced a doubling in the output of [3H]5-HT newly synthesized from [3H]tryptophan. The releasing effect of K+ was enhanced in the presence of methiothepin. In contrast, LSD partially inhibited the K+-induced release of [3H]5-HT. These changes induced by methiothepin and LSD were also observed in experiments with tissues from newborn- rats. Therefore, it could be concluded that the feedback mechanisms triggered by (presynaptic) serotoninergic receptors could regulate 5-HT release immediately after birth. The delayed occurrence of the negative feedback process controlling 5-HT synthesis (after LSD treatment) might suggest that the regulation of 5-HT synthesis is not related to 5-HT release during the early life period.
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