ACUTE ADMINISTRATION OF A TRYPTOPHAN-FREE AMINO-ACID MIXTURE DECREASES 5-HT RELEASE IN RAT HIPPOCAMPUS IN-VIVO

The effect of oral administration of a tryptophan-free amino acid mixt ure or the same mixture containing tryptophan (Trp) on hippocampal ser otonin (5-HT) extracellular levels was studied using in vivo brain mic rodialysis of freely moving rats. During chloral hydrate anesthesia ra ts were implanted with dialysis probes in the dorsal hippocampus, and experiments were performed 24 h later. In vehicle-treated rats, the ex tracellular levels of 5-hydroxyindolacetic acid (5-HIAA) and 5-HT did not change during 240 min after ingestion. Oral administration of the Trp-free amino acid mixture significantly decreased basal 5-HT and 5-H IAA output 100 min after ingestion (65 and 81% of basal value, respect ively) and remained at this level for another 140 min. The amino acid mixture containing Trp failed to significantly change basal extracellu lar levels of 5-HT, but enhanced that of 5-HIAA by similar to 134%. Mo reover, in rats receiving the Trp-free amino acid mixture, the increas e of hippocampal 5-HT release induced by d-fenfluramine (206%) was sma ller than that released by the same drug in rats receiving the nutriti onally balanced amino acid mixture (271%). Thus these results show tha t removal of Trp from the balanced amino acid mixture decreases sponta neous and d-fenfluramine-induced release of 5-HT in the hippocampus. I n conclusion, our study supports the hypothesis that the mood-lowering effect observed in man after ingestion of a Trp-free amino acid mixtu re is associated with diminished 5-HT release in the brain.