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

Background 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. Aims 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. Method 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. Results 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. Conclusions Decreased tyrosine availability to the brain attenuates pathological increases in dopamine neurotransmission following methamphetamine administration and putatively in mania.