Document Detail

Effect of acute tyrosine depletion in using a branched chain amino-acid mixture on dopamine neurotransmission in the rat brain.
MedLine Citation:
PMID:  16034439     Owner:  NLM     Status:  MEDLINE    
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.
Marisa Le Masurier; Weite Oldenzeil; Claire Lehman; Philip Cowen; Trevor Sharp
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  31     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-19     Completed Date:  2006-07-06     Revised Date:  2011-05-18    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  310-7     Citation Subset:  IM    
Department of Pharmacology, Oxford University, UK.
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MeSH Terms
3,4-Dihydroxyphenylacetic Acid / metabolism
5-Hydroxytryptophan / metabolism
Amino Acids, Branched-Chain / pharmacology*
Amphetamine / pharmacology
Analysis of Variance
Behavior, Animal / drug effects
Brain / anatomy & histology,  drug effects*
Brain Chemistry / drug effects*
Catecholamines / metabolism
Cell Count / methods
Dopamine / metabolism*
Dopamine Agents / pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Immunohistochemistry / methods
Microdialysis / methods
Motor Activity / drug effects
Oncogene Proteins v-fos / metabolism
Rats, Sprague-Dawley
Serotonin / metabolism
Time Factors
Tyrosine / deficiency*,  pharmacology
Reg. No./Substance:
0/Amino Acids, Branched-Chain; 0/Catecholamines; 0/Dopamine Agents; 0/Oncogene Proteins v-fos; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 300-62-9/Amphetamine; 50-67-9/Serotonin; 55520-40-6/Tyrosine; 56-69-9/5-Hydroxytryptophan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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