ROLE OF INTRANEURONAL AMINE LEVELS IN FEEDBACK-CONTROL OF DOPAMINE, NORADRENALINE AND 5-HYDROXYTRYPTAMINE SYNTHESIS IN RAT-BRAIN

The influence of varying brain levels of dopamine, noradrenaline and 5-HT [5-hydroxytryptamine] on their respective synthesis rates was investigated. The 1st step in monoamine synthesis was studied in vivo by measuring the accumulation of dopa and 5-hydroxytryptophan after inhibition of the aromatic L-amino acid decarboxylase. Variations in monoamine levels were obtained by combined treatment with inhibitors of the decarboxylase (NSD 1015 [3-hydroxybenzylhydrazine hydrochloride] or Ro 4-4602 [benserazide]) and of monoamine oxidase (pargyline). An increase in monoamine levels by pargyline inhibited the synthesis of dopamine, noradrenaline and 5-HT. A decrease in monoamine levels induced by the decarboxylase inhibitor Ro 4-4602 appeared to stimulate dopamine and noradrenaline synthesis but had no effect on 5-HT synthesis. The influence of varying levels of dopamine and noradrenaline on the synthesis of these amines could still be demonstrated after blockade of dopamine receptors and of .alpha.-adrenergic (noradrenaline) receptors by haloperidol, suggesting that the mechanism involved in this feedback control is mediated via end-product inhibition of tyrosine hydroxylase. The stimulating influence of haloperidol on the synthesis of catecholamines did not seem to be directly related to changes in catecholamine levels. The short-term control of catecholamine synthesis presumably involves 2 independent feedback mechanisms, 1 intraneuronal mechanism operating via end-product inhibition and 1 synaptic mechanism mediated via dopamine and noradrenaline receptors, respectively. Both pre- and postsynaptic receptors may be involved in the latter mechanism.