5-Hydroxy-L-tryptophan suppresses food intake in food-deprived and stressed rats

Pharmacol Biochem Behav. 2004 Jan;77(1):137-43. doi: 10.1016/j.pbb.2003.10.011.

Abstract

Giving L-tryptophan, serotonin's circulating precursor, or a serotonin-releasing drug can decrease food intake and body weight. Giving 5-hydroxy-L-tryptophan (5-HTP), serotonin's immediate intracellular precursor, has been thought to be ineffective in enhancing brain serotonin synthesis unless it is coadministered with a dopa decarboxylase inhibitor to protect 5-HTP from destruction outside the brain. We have examined the effect of 5-HTP on food consumption and tissue 5-HTP levels among rats subjected to two different hyperphagic stimuli, food deprivation and a standardized stress (tail pinch), and on plasma 5-HTP levels in humans. In rats, 5-HTP (3-200 mg/kg ip) suppressed food intake in a dose-dependent manner in both models, but was at least eight times more effective in our stress-hyperphagia model. (Differences in the two procedures might have contributed to the observed differences in potencies.) This suppression was blocked by coadministration of another large neutral amino acid (LNAA), L-valine. Brain 5-HTP levels correlated significantly with peak plasma 5-HTP (r(2)=.69) or 5-HTP/LNAA (r(2)=.81) levels. Additionally, among humans, oral 5-HTP (1.2-2.0 mg/kg) produced, after 1 and 2 h, a significant increase in plasma 5-HTP (1.5- to 2.3-fold). These observations suggest that 5-HTP may be useful in controlling the excessive food intake sometimes generated by stress, even if given without decarboxylase inhibitors or other drugs.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5-Hydroxytryptophan / blood
  • 5-Hydroxytryptophan / pharmacology
  • 5-Hydroxytryptophan / therapeutic use*
  • Administration, Oral
  • Adult
  • Analysis of Variance
  • Animals
  • Brain / metabolism
  • Cross-Over Studies
  • Eating / drug effects*
  • Eating / physiology
  • Female
  • Food Deprivation* / physiology
  • Humans
  • Injections, Intraperitoneal
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological / drug therapy
  • Stress, Physiological / metabolism
  • Stress, Physiological / psychology*

Substances

  • 5-Hydroxytryptophan