5-Hydroxy-L-tryptophan suppresses food intake in food-deprived and stressed rats.
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.
Amer
Ahmed
A
Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA.
Breu
Jeff
J
McDermott
Janine
J
Wurtman
Richard J
RJ
Maher
Timothy J
TJ
D006916:5-Hydroxytryptophan / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism; D018592:Cross-Over Studies; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology*
D006916:5-Hydroxytryptophan