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Hamon M, Glowinski J. 
“Regulatlon of Serotonin Synthesis.”. 
Life Sci. 1974;15(9):1533-1548.
Regulation of serotonin synthesis was reviewed When rats are injected with high doses of tryptophan there is an immediate increase in 5 - HT synthesis, and conversely, when tryptophan levels are reduced following activation of tryptophan pyrrolase by a-methyltryptophan or hydrocortisone, serotonin synthesis is reduced. However, changes in the levels of free tryptophan in the plasma are not necessarily associated with changes in 5-HT synthesis e.g. probenecid and chlordiazepoxide increase the level of free tryptophan but do not stimulate 5-HT synthesis. Insulin which increases the tryptophan bound to albumin paradoxically enhances tryptophan levels and 5-HT synthesis in the brain. Some workers postulate that the regulation of central 5-HT synthesis is dependent on the equilibrium between tryptophan and other neutral amino acids. Many studies have indicated that 5-HT synthesis is not only dependent on tryptophan levels in plasma but is also regulated by changes in activity of the amino acid carrier. Imipramine, chlorimipramine and cocain inhibit both 5-HT synthesis and amino acid transport in brain slices and synaptosomes while dibutyryl cyclic AMP induces opposite effects in cortical slices. LSD inhibits 5-HT synthesis and is associated with decreased tryptophan transport. Reserpine and lithium have similar effects. Further studies have indicated that in some cases changes in 5-HT synthesis may be dependent on the compartmentalization of tryptophan. Rapid changes in 5-HT synthesis have also been observed associated with fluctuations in transmitter release which are independent of the peripheral metabolism of tryptophan; they also seem to be unrelated to changes in tryptophan transport in brain tissue. Sustained changes in the rate of 5-HT synthesis can be related to modifications in the concentration of tryptophan hydroxylase in serotoninergic neurons. - The way in which serotoninergic neurons integrate all these regulating factors to modulate 5-HT synthesis is still unknown.
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