Effect of a tyrosine-free amino acid mixture on regional brain catecholamine synthesis and release

• Published in: Psychopharmacologia 1999-01, Vol.141 (2), p.182-188
• Main Authors: MCTAVISH, S. F. B, COWEN, P. J, SHARP, T
• Format: Article
• Language: English
• Subjects: Amino acids; Amino Acids - pharmacology; Amphetamines; Animals; Biochemistry and metabolism; Biological and medical sciences; Brain; Brain - drug effects; Brain - metabolism; Catecholamines; Catecholamines - biosynthesis; Catecholamines - metabolism; Central nervous system; Corpus Striatum - metabolism; Cortex (frontal); Dihydroxyphenylalanine; Dopamine; Dopamine - metabolism; Dopamine receptors; Fundamental and applied biological sciences. Psychology; Hippocampus; Hippocampus - metabolism; Hypothalamus; Innervation; Male; Microdialysis; Neostriatum; Norepinephrine; Norepinephrine - metabolism; Nucleus accumbens; Rats; Rats, Sprague-Dawley; Serotonin - biosynthesis; Tyrosine; Tyrosine - deficiency; Tyrosine - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130050823

We report the effects of a tyrosine (and phenylalanine)-free amino acid mixture on tyrosine levels, ex vivo catecholamine synthesis and in vivo catecholamine release in brain regions of the rat. Administration of a tyrosine-free amino acid load reduced tissue levels of tyrosine (-50% after 2 h) in all brain regions examined (frontal cortex, hippocampus, striatum). The tyrosine-free amino acid mixture also reduced DOPA accumulation: this effect was most marked in striatum (-44%) and nucleus accumbens (-34%), areas with a predominantly dopaminergic innervation. Smaller decreases (-20-24%) were detected in other areas (cortex, hippocampus and hypothalamus). The effect on DOPA accumulation was prevented by supplementing the mixture with tyrosine/phenylalanine. The tyrosine-free amino acid mixture did not alter 5-HTP accumulation in any region. In microdialysis experiments, the tyrosine-free amino acid mixture did not consistently alter striatal extracellular dopamine under basal conditions but markedly, and dose-dependently, reduced the release of dopamine induced by amphetamine. In contrast, the tyrosine-free amino acid mixture did not alter either basal or amphetamine-evoked release of noradrenaline in hippocampus. Overall, these studies indicate that administration of a tyrosine-free amino acid mixture to rats depletes brain tyrosine to cause a decrease in regional brain catecholamine synthesis and release. Dopaminergic neurones appear to be more vulnerable to tyrosine depletion than noradrenergic neurones.