dl-5-Hydroxytryptophan-induced changes in central monoamine neurons after peripheral decarboxylase inhibition

Abstract

Abstract The histochemical effects of 500 and 1000 mg/kg of dl-5-hydroxy-tryptophan (5-HTP), both alone and in combination with a peripheral decarboxylase inhibitor (seryl-trihydroxy benzyl hydrazine; Ro 4–4602) have been examined on central monoamine neurons of rats by the Falck-Hillarp fluorescence technique that demonstrates monoamines and their precursors. 5-HTP alone or together with Ro 4–4602 caused only weak intraneuronal accumulation of 5-HT in the central 5-HT neurons, in spite of an increased entry of 5-HTP into the brain after Ro 4–4602 treatment, as shown by an increase in the specific neuropil fluorescence and a reduction of 5-HT accumulation in the cells of the capillary walls. Ro 4–4602 markedly potentiated the effects of 5-HTP on the central dopamine neurons, many of which became clearly yellow fluorescent. The mechanism of dopamine depletion by 5-HTP is probably therefore mainly one of displacement. The effects on the noradrenaline neurons were also potentiated by Ro 4–4602 pretreatment, the neurons exhibiting a yellow-green fluorescence. This depletion may therefore also be mainly be due to amine displacement. It is concluded that the ability of the 5-HT neurons to take up and accumulate 5-HT in the presence of 5-HTP is relatively low in spite of large amounts of 5-HTP present in the brain neuropil after extracerebral decarboxylase inhibition.