Calcium-dependent, tetrodotoxin-sensitive stimulation of cortical serotonin release after a tryptophan load.
The effect of intraperitoneal administration of tryptophan (50, 100, or 200 mg/kg) on extracellular concentrations of tryptophan, serotonin (5-hydroxytryptamine, 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) was studied in the cortex of freely moving rats by transcerebral dialysis. Rats were implanted with dialysis probes in the frontal cortex, and experiments were performed 24 h later. Tryptophan, 5-HT, and 5-HIAA were quantified in 20-min samples of dialysate by HPLC with electrochemical detection after separation on reverse-phase columns. Tryptophan administration resulted in a significant increase of tryptophan, 5-HT, and 5-HIAA levels in dialysates. The maximal increase of 5-HT and 5-HIAA output was approximately 150% over basal values. Perfusion with Ringer's solution containing tetrodotoxin (1 microM) reduced 5-HT output by 90% and prevented the increase of 5-HT and 5-HIAA content after 100 mg/kg of tryptophan. Similar results were obtained after perfusion with Ringer's solution without Ca2+. The results indicate that a tryptophan load stimulates the physiological release of 5-HT.
Carboni
E
E
Institute of Experimental Pharmacology and Toxicology, University of Cagliari, Italy.
Cadoni
C
C
Tanda
G L
GL
Di Chiara
G
G
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology*; D014364:Tryptophan / Q000378:metabolism / Q000494:pharmacology*
D012701:Serotonin; D013779:Tetrodotoxin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D002118:Calcium