Differential uptake, metabolism and behavioral effects of the D and L isomers of 5-hydroxytryptophan

P. E. Penn, W. J. McBride, J. N. Hingtgen, M. H. Aprison

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Abstract

The relative contribution of the D and L isomers of 5-hydroxytryptophan (5-HTP) to the uptake and metabolism of 5-HTP and their associated behavioral effects were investigated. For the metabolic study, an injection of 25 mg/kg of D or L-5-HTP was administered IP and the rats killed 15, 30, 45 or 60 min later. Endogenous levels of 5-HTP, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the telencephalon following D- or L-5-HTP administration. Levels of 5-HTP, 5-HT and 5-HIAA were also measured in the brain stem (including diencephalon) following L-5-HTP administration. In the behavioral study, the effects of IP injections of D-5-HTP, L-5-HTP and D,L-5-HTP upon operant responding on a VI 1 schedule were investigated. Compared to vehicle controls, L-5-HTP significantly increased the levels of 5-HTP, 5-HT and 5-HIAA in the telencephalon and brain stem at all time points investigated. Behaviorally, 25 mg/kg of L-5-HTP and 50 mg/kg of D,L-5-HTP produced similar changes. Following the injection of either compound there was a large decrease in response rate with a duration of about 1 hr which paralleled the neurochemical changes. Injections of D-5-HTP produced an increase in the levels of 5-HTP and 5-HIAA in the telencephalon at 15 min but no change in the level of 5-HT was observed. In the operant situation, following D-5-HTP injections, a brief decrease in responding occurred in some animals which did not correlate with the neurochemical data. It was concluded that the L isomer is mainly responsible for the neurochemical and behavioral effects seen when D,L-5-HTP is administered.

Original languageEnglish (US)
Pages (from-to)515-518
Number of pages4
JournalPharmacology, Biochemistry and Behavior
Volume7
Issue number6
DOIs
StatePublished - Dec 1977

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Keywords

  • Behavior
  • D-5-Hydroxytryptophan
  • L-5-Hydroxytryptophan
  • Metabolism
  • Serotonin

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

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