Feedback Regulation of 5‐ht Synthesis in Rat Striatal Slices

The effects of changes in intraneuronal levels of 5‐HT induced by monoamine oxidase inhibitors (MAOI) given in vivo or exogenous 5‐HT added in vitro on 5‐HT synthesis in striatal slices of the rat have been examined. The synthesis of 5‐HT was estimated by the measurement of the total formation of [ 3 H]5‐HT and [ 3 H]5‐hydroxyindole acetic acid from [ 3 H]tryptophan and by calculation of the conversion index (CI) of tryptophan into 5‐HT. The small formation of [ 3 H]tryptamine and [ 3 H]indole acetic acid from [ 3 H]tryptophan was taken into account in the estimation of 5‐HT synthesis. Both MAOI pretreament (180 min) and 5‐HT (2·8 μM) inhibited synthesis. The latter effect persisted in catecholamine depleted tissues and was related to intraneuronal changes in 5‐HT levels, since it could be prevented by chlorimipramine. The inhibition of 5‐HT synthesis was related to the decreased conversion of tryptophan into 5‐hydroxytryptophan and could not be prevented by p‐chloro‐phenylalanine pretreatment which depleted 5‐HT levels or by dibutyryl cyclic AMP which normally stimulated 5‐HT synthesis. Tryptophan uptake in slices was not affected by exogenous 5‐HT. The various mechanisms possibly involved in the end product regulation process of 5‐HT synthesis are discussed.