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

Abstract

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.