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Effect of Acute Tyrosine Depletion in Using a Branched Chain Amino-Acid Mixture on Dopamine Neurotra

Effect of Acute Tyrosine Depletion in Using a Branched Chain Amino-Acid Mixture on Dopamine Neurotra

  1. NeuroChi
    Central dopamine function is reduced by decreasing the availability of the catecholamine precursor, tyrosine, using a tyrosine-free amino
    acid mixture containing multiple large neutral as well as branched chain amino-acids, which compete with tyrosine for uptake into the
    brain. Current mixtures are cumbersome to make and administer, and unpalatable to patients and volunteers. Here, we investigate
    whether individual or limited amino-acid combinations could reduce brain tyrosine levels and hence dopamine function. Measurements
    of regional brain tyrosine levels, catecholamine and indoleamine synthesis (L-DOPA and 5-HTP accumulation, respectively) were used to
    identify an effective paradigm to test in neurochemical, behavioral and fos immunocytochemical models. Administration of leucine or
    isoleucine, or a mixture of leucine, isoleucine, and valine reduced tyrosine and 5-HTP, but not L-DOPA accumulation. A mixture of
    leucine, valine, and isoleucine supplemented with tryptophan reduced brain tyrosine and L-DOPA, but not 5-HTP. In microdialysis
    experiments this amino-acid mixture reduced basal and amphetamine-evoked striatal dopamine release, as well as amphetamine-induced
    hyperactivity. This mixture also reduced amphetamine-induced fos expression in striatal areas. In conclusion, the present study identified a
    small combination of amino acids that reduces brain tyrosine and dopamine function in a manner similar to mixtures of multiple amino
    acids. This minimal mixture may have use as a dopamine reducing paradigm in patient and volunteer studies.
    Neuropsychopharmacology (2006) 31, 310–317. doi:10.1038/sj.npp.1300835; published online 20 July 2005

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