Antidopaminergic effects of dietary tyrosine depletion in healthy subjects and patients with manic illness

<jats:sec><jats:title>Background</jats:title><jats:p>In rats, amino acid mixtures lacking tyrosine and its precursor phenylalanine decrease the release of dopamine produced by the psychostimulant drug amphetamine. Amphetamine has been proposed as a model for clinical mania.</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>To assess whether dietary tyrosine depletion attenuates the psychostimulant effects of methamphetamine in healthy volunteers and diminishes the severity of mania in acutely ill patients.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>Sixteen healthy volunteers received a tyrosine-free amino acid mixture and a control mixture in a double-blind crossover design 4 h before methamphetamine (0.15 mg/kg). Twenty in-patients meeting DSM–IV criteria for mania were allocated blindly and randomly to receive either the tyrosine-free mixture or the control mixture.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The tyrosine-free mixture lowered both subjective and objective measures of the psychostimulant effects of methamphetamine. Ratings of mania were lower in the patients who received the tyrosine-free mixture.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Decreased tyrosine availability to the brain attenuates pathological increases in dopamine neurotransmission following methamphetamine administration and putatively in mania.</jats:p></jats:sec>