ORIGINAL INVESTIGATION

Psychopharmacology

, Volume 141, Issue 2, pp 182-188

First online:

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

  • Sarah F. B. McTavishAffiliated withUniversity of Oxford Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, Oxford, UK
  • , Philip J. CowenAffiliated withUniversity Department of Psychiatry, Warneford Hospital, Oxford, UK e-mail: trevor.sharp@clinpharm.ox.ac.uk, Fax: +44-1865-791712
  • , T. SharpAffiliated withUniversity of Oxford Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, Oxford, UK

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Abstract

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.

Key words Tyrosine depletion Catecholamine Dopamine Noradrenaline Microdialysis