EFFECT OF PSYCHOTROPIC DRUGS ON TRYPTOPHAN CONCENTRATION IN THE RAT BRAIN

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 177; no. 3; pp. 475 - 480
• Main Authors: Tagliamonte, A, Tagliamonte, P, Perez-Cruet, J, Stern, S, Gessa, G L
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.06.1971
• Subjects: Alkaloids - pharmacology; Animals; Apomorphine - pharmacology; Aporphines - pharmacology; Body Temperature; Brain Chemistry - drug effects; Butyrates - pharmacology; Chlorpromazine - pharmacology; Cold Temperature; Cyclic AMP - pharmacology; Dextroamphetamine - pharmacology; Fenclonine - pharmacology; Fenfluramine - pharmacology; Haloperidol - pharmacology; Hot Temperature; Hydroxybutyrates - pharmacology; Hydroxyindoleacetic Acid - analysis; Lithium - pharmacology; Male; Methyltyrosines - pharmacology; Morphine - pharmacology; Nucleosides - pharmacology; Phenelzine - pharmacology; Phenmetrazine - pharmacology; Probenecid - pharmacology; Rats; Reserpine - pharmacology; Serotonin - biosynthesis; Tryptophan - analysis; Tryptophan - blood; Tyrosine - analysis; Tyrosine - blood
• ISSN: 0022-3565; 1521-0103

The administration of d -amphetamine. reserpine, dibutyryl cyclic adenosine monophosphate and lithium or the exposure to hot environmental temperature, conditions known to increase brain serotonin synthesis, increased tryptophan concentration in brain by more than 100%. Brain tryptophan concentration was also markedly increased by phenmetrazine, phenelzine, dl -fenfluramine, bulbocapnine, γ-hydroxybutyrate and probenecid. On the other hand, p -chlorophenylalanine which inhibits serotonin synthesis decreased brain tryptophan level by about 50%. Morphine, apomorphine, chlorpromazine, α-methyltyrosine, haloperidol or exposure to cold environment did not change brain tryptophan level. Changes in tyrosine levels in brain were similar, but less pronounced than those of brain tryptophan. The increase in brain tryptophan could be dissociated from changes in plasma tryptophan and in body temperature. However, when body temperature rose above 40°C the rise in brain tryptophan was associated with a proportional rise in plasma tryptophan. Since the concentrations of tryptophan normally present in the mammalian brain are below the K m for tryptophan hydroxylase, all drugs capable of increasing tryptophan level in brain should also stimulate serotonin synthesis. Accordingly, treatments found to increase brain tryptophan level also increased that of brain 5-hydroxyindoleacetic acid. Tryptophan measurements in brain might be used in screening for drugs affecting serotonin turnover.