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

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.