Long Term Effects of Midbrain Stimulation on 5-Hydroxyindole Synthesis in Rat Brain

Abstract

THE association between brain monoamines and nerve terminals has been interpreted as evidence of a neuro-transmitter function. It has been shown that serotonin (5-hydroxytryptamine, 5HT) is localized in fine neurones which project to the forebrain. and whose cell bodies lie in the raphé nuclei of the midbrain^1,2. The transmitter hypothesis has been further substantiated by the finding that stimulation of these nuclei increases forebrain levels of 5-hydroxyindol-3-ylacetic acid (5HIAA), the metabolite of 5HT³, and increases the release of 5HT from brain into cortical cups⁴. Using the rate of formation of 5-hydroxy-indoles after tryptophan administration in vivo as an index of the rate of hydroxylation of tryptophan⁵, the limiting step in the synthesis of 5HT, stimulation has been shown not only to increase release of 5HT but also to accelerate the rate of production of the amine (unpublished observations of D. Eccleston, M. Randic and A. Padjen). This could arise from immediate electrical effects on membrane permeability with changes in transport of substrate to existing enzyme. We have examined whether the increased rate of amine production continues after stimulation has ceased, which would suggest that the stimulation caused enzyme induction.