In vivo release of 5-HT in the lateral ventricle of the rat: effects of 5-hydroxytryptophan and tryptophan.

The in vivo release of 5-HT was examined in the rat brain. For this purpose, the left lateral ventricle was perfused at a constant rate with an artificial CSF for several hours in animals anaesthetized with halothane. 5-HT was estimated in serial 1-h collected fractions. The amine was first isolated by adsorption on a Sephadex G-10 column and then assayed using the radioenzymatic method of Saavedra et al.37, slightly modified to improve its sensitivity. The quantity of 5-HT released spontaneously during the first hour fraction was 296 pg, it was lower (99 pg/h) in the following fractions. 5-HT released into the CSF may in great part originate from serotoninergic terminals localized in structures surrounding the ventricle. This was suggested by experiments in which exogenous [3H]5-HT or [3H]tryptophan were perfused through the lateral ventricle during a few hours. [3H]5-HT taken up or synthetized was mainly localized in structures surrounding the ventricular space. The acute injection of 5-hydroxytryptophan (100 mg/kg) induced an immediate important and long lasting increase of 5-HT release. In contrast the acute injection of tryptophan (100 mg/kg) led to a transient and moderate elevation of 5-HT release which was only detected during the second hour of perfusion. Curiously a similar pattern of transmitter release was observed following the constant intravenous infusion of the amino acid (70 mg/kg/h) except that the increase in 5-HT release was much more pronounced during the second hour than after the acute injection. Parallel experiments were made to determine the time course of the changes of free and total tryptophan levels in plasma and of those of tryptophan, 5-HT, and 5-hydroxyindoleacetic-acid (5-HIAA) in brain tissues, induced by the acute and long term administrations of tryptophan. Moreover the rate of 5-HT synthesis was estimated using the monoamine oxidase inhibition method 2 and 5 h after both tryptophan treatments in halothane anaesthetized rats. 5-HT levels and the synthesis rate of the transmitter were increased at 2 h (when both tryptophan treatments stimulated 5-HT release). Despite the presence of high tryptophan levels in plasma and tissues and of high 5-HT and 5-HIAA levels in tissues, the synthesis rate of 5-HT (as the 5-HT release) was similar to that of controls 5 h after the onset of tryptophan infusion. These results suggest that some relationships occurred between the changes in 5-HT SYNTHESIs and release after the first hour of perfusion. The absence of effects of tryptophan treatments on 5-HT release during the first hour of perfusion are also discussed.