RESUMEN
Tryptamine-4,5-dione (4,5-DKT) a neurotoxic derivative of serotonin (5-HT), was injected into the lateral ventricle of the rat in order to evaluate its biochemical effects. The levels of 8 substances in the hippocampus, striatum and prefrontal cortex were examined 3, 7 and 14 days after treatment with 4,5-DKT. 5-Hydroxytryptamine and 5-hydroxyindoleacetic acid (5-HIAA) levels were decreased in all three regions by days 7 and 14, respectively. Tryptamine-4,5-dione had no significant effect on dopaminergic or adrenergic systems or on the levels of L-tryptophan and L-tyrosine, in any of the three areas of brain examined. Reduced activity of tryptophan hydroxylase in the cortex was observed 14 days after administration of 4,5-DKT. However, administration of 4,5-DKT did not alter the binding of [3H]paroxetine, a specific antagonist of the uptake of 5-HT, to nerve terminals. These results indicate that 4,5-DKT produced depletion of 5-HT without eliminating serotoninergic nerve terminals.
Asunto(s)
Química Encefálica/efectos de los fármacos , Indolquinonas , Triptaminas/farmacología , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Electroquímica , Ácido Hidroxiindolacético/metabolismo , Técnicas In Vitro , Inyecciones Intraventriculares , Masculino , Membranas/efectos de los fármacos , Membranas/metabolismo , Neurotransmisores/metabolismo , Paroxetina , Piperidinas/farmacología , Ratas , Ratas Endogámicas , Serotonina/metabolismo , Antagonistas de la Serotonina/farmacología , Triptaminas/administración & dosificación , Triptófano Hidroxilasa/metabolismoRESUMEN
A partially oxidized serotonin (5-HT) was synthesized electrochemically from 5-HT in an acidic solution. This compound was characterized by its chromatographic and electrochemical properties and identified by mass spectroscopy and NMR as tryptamine-4,5-dione (4,5-DKT). In in vitro superfusion experiments, 10(-5)M 4,5-DKT significantly increased the basal 5-HT efflux from both rat hippocampal and striatal fragments. In contrast, 10(-5) M 4,5-DKT did not change the release of dopamine or its metabolite, 3,4-dihydroxyphenylacetic acid from striatal fragments. Continuous perfusion of 4,5-DKT did not modify the effect of KCl on either 5-HT or dopamine release from both brain areas. In in vitro incubation experiments, 10(-8) to 10(-5) M 4,5-DKT evoked 5-HT efflux from rat hippocampus in a dose-dependent fashion. When 10(-4) and 10(-5) M fluoxetine was incubated with 10(-6) M 4,5-DKT, it partially blocked 4,5-DKT-induced 5-HT release. Pargyline, at 10(-5) M inhibited significantly the 5-hydroxyin-doleacetic acid efflux, but did not modify the 4,5-DKT-stimulated 5-HT release. Incubation of 4,5-DKT with glutathione (GSH) and mercaptoethanol indicated that 4,5-DKT binds to sulfhydryl groups. An evidence of GSH-4,5-DKT conjugate was also observed after incubation of 4,5-DKT with a brain homogenate. The interaction of 4,5-DKT with GSH or mercaptoethanol was blocked effectively with N-ethylmaleimide. It is possible that sulfhydryl groups are involved in the mechanism of 4,5-DKT action on 5-HT release.