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.


OBJECTIVE
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.


METHODS
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.
McTavish
S F
SF
University Department of Psychiatry, Neurosciences Building, Warneford Hospital, Oxford OX3 7JX, UK. sarah.mctavish@psychiatry.oxford.ac.uk
McPherson
M H
MH
Harmer
C J
CJ
Clark
L
L
Sharp
T
T
Goodwin
G M
GM
Cowen
P J
PJ
D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004298:Dopamine / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D014443:Tyrosine / Q000008:administration & dosage / Q000172:deficiency*
D000697:Central Nervous System Stimulants; D014443:Tyrosine; D008694:Methamphetamine; D004298:Dopamine