5-Hydroxytryptamine: the effects of impaired synthesis on its metabolism and release in rat.
1 Control rats given L-tryptophan (100 mg/kg) showed a smaller increase of brain 5-hydroxytryptamine (5-HT) than its metabolite 5-hydroxyindoleacetic acid (5-HIAA). However, when brain 5-HT concentrations were depleted by 40-50% after treatment with the synthesis inhibitor p-chlorophenylalanine (PCPA) (150 mg/kg) L-tryptophan caused a considerable increase in 5-HT but no change in 5-HIAA. Similar results were obtained following depletion of brain 5-HT by pretreatment with p-chloroamphetamine (10 mg/kg).2 Electrical stimulation of the median raphe nucleus of control rats significantly increased 5-HIAA in the hypothalamus, hippocampus and striatum. However, stimulation of PCPA (200 mg/kg) pretreated animals did not significantly increase 5-H1AA either 24 or 72 h after administration of the drug.3 Pretreatment of rats with PCPA (200 mg/kg) increased striatal synaptosomal uptake of [(3)H]-5HT by 30% and reduced 5-HT concentration in the rest of the brain by 62%.4 PCPA (150 mg/kg) markedly reduced the acute behavioural response (-76%) to p-chloroamphetamine (10 mg/kg) although brain 5-HT was only moderately reduced (-36%). L-Tryptophan (100 mg/kg) given 15 min before p-chloroamphetamine restored both brain 5-HT and the behavioural effects of p-chloroamphetamine in PCPA pretreated rats and enhanced the behavioural response to p-chloroamphetamine in control rats.5 The results suggest that newly synthesized 5-HT is less rapidly metabolized in rats with low brain 5-HT. The possible reasons for this and the relevance of the results to the use of L-tryptophan in the treatment of depressive illness are discussed.
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D001923:Brain Chemistry / Q000187:drug effects; D004558:Electric Stimulation; D010134:Fenclonine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D066298:In Vitro Techniques; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D012701:Serotonin / Q000096:biosynthesis*; D013574:Synaptosomes / Q000378:metabolism; D014364:Tryptophan / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000494:pharmacology
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D010133:p-Chloroamphetamine; D014364:Tryptophan; D010134:Fenclonine