Functional cerebral activity of an analogue of serotonin formed in situ.

Reduction of the serotonin content of the brain of rats (specifically in the medial raphe nucleus) by various means results in spontaneous increase of adrenal tyrosine hydroxylase activity. This neurally mediated induction is attenuated by appropriate administration of the serotonin precursor 5-hydroxytryptophan to the animals, along with carbidopa (Quik and Sourkes, J. Neurochem.28, 137, 1977). In the present work adrenal tyrosine hydroxylase was induced by giving rats either the neurotoxin 5,7-dihydroxytryptamine (injected into the cerebral ventricles) or the monoamine depletor reserpine (given intraperitoneally). Other rats received alpha-methyltryptophan. This amino acid causes a marked decline of the serotonin content of the brain, but gives rise to relatively large amounts of alpha-methylserotonin in that organ (Roberge et al., Neuropharmacology11, 197, 1972). Alpha-methyltryptophan had no effect on adrenal tyrosine hydroxylase activity but, when it was given with dihydroxytryptamine or reserpine, it prevented the induction of adrenal tyrosine hydroxylase that otherwise occurred. The results are discussed in relation to the effect of alpha-methyltryptophan on the content of indoles (tryptophan, serotonin, 5-hydroxyindoleacetic acid, alpha-methyltryptophan, alpha-methylserotonin) in the plasma and brain, as detected by HPLC. It is concluded that alpha-methylserotonin can functionally replace cerebral serotonin, at least in relation to the transneuronal regulation of adrenal tyrosine hydroxylase activity.