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Acute phenylalanine/tyrosine depletion of phasic dopamine in the rat brain

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A Correction to this article was published on 10 August 2018

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Abstract

Rationale

Dopamine plays a critical role in striatal and cortical function, and depletion of the dopamine precursors phenylalanine and tyrosine is used in humans to temporarily reduce dopamine and probe the role of dopamine in behavior. This method has been shown to alter addiction-related behaviors and cognitive functioning presumably by reducing dopamine transmission, but it is unclear what specific aspects of dopamine transmission are altered.

Objectives

We performed this study to confirm that administration of an amino acid mixture omitting phenylalanine and tyrosine (Phe/Tyr[−]) reduces tyrosine tissue content in the prefrontal cortex (PFC) and nucleus accumbens (NAc), and to test the hypothesis that Phe/Tyr[−] administration reduces phasic dopamine release in the NAc.

Methods

Rats were injected with a Phe/Tyr[−] amino acid mixture, a control amino acid mixture, or saline. High-performance liquid chromatography was used to determine the concentration of tyrosine, dopamine, or norepinephrine in tissue punches from the PFC and ventral striatum. In a separate group of rats, phasic dopamine release was measured with fast-scan cyclic voltammetry in the NAc core after injection with either the Phe/Tyr[−] mixture or the control amino acid solution.

Results

Phe/Tyr[−] reduced tyrosine content in the PFC and NAc, but dopamine and norepinephrine tissue content were not reduced. Moreover, Phe/Tyr[−] decreased the frequency of dopamine transients, but not their amplitude, in freely moving rats.

Conclusions

These results indicate that depletion of tyrosine via Phe/Tyr[−] decreases phasic dopamine transmission, providing insight into the mechanism by which this method modifies dopamine-dependent behaviors in human imaging studies.

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Change history

  • 10 August 2018

    After publication of this paper, the authors determined an error in the calculation of the norepinephrine standard concentrations for the HPLC calibration curves.

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Acknowledgments

Authors thank Dr. Paul Kropp for consultation on protocols for the amino acid mixtures, Dr. Chris Wiesen (UNC Odum Institute for Research in Social Science) for statistical consultation, and Drs. Margaret Broadwater and Aric Madayag for technical assistance and critical comments on the manuscript.

Author contribution

DLR and CAB conceptualized the experiments. TAS, SCT, DLR, and WL collected and analyzed the voltammetric data. SJS, SZ, RUC, JMD, and RAG set up HPLC procedures and collected and analyzed the tissue content data. DLR, TAS, SJS, SZ, CAB, and RAG interpreted the data and prepared the manuscript.

Author information

Authors and Affiliations

  1. Bowles Center for Alcohol Studies, University of North Carolina, CB #7178, Chapel Hill, NC, 27599-7178, USA

    Tatiana A. Shnitko, Sarah C. Taylor, Sierra J. Stringfield, William B. Lynch, Charlotte A. Boettiger & Donita L. Robinson

  2. Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC, USA

    Sierra J. Stringfield, Charlotte A. Boettiger & Donita L. Robinson

  3. Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA

    Shannon L. Zandy, Roberto U. Cofresí, James M. Doherty & Rueben A. Gonzales

  4. Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA

    Charlotte A. Boettiger

  5. Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA

    Donita L. Robinson

Authors
  1. Tatiana A. Shnitko
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  2. Sarah C. Taylor
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  4. Shannon L. Zandy
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  5. Roberto U. Cofresí
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  6. James M. Doherty
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  7. William B. Lynch
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  8. Charlotte A. Boettiger
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  9. Rueben A. Gonzales
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  10. Donita L. Robinson
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Corresponding author

Correspondence to Donita L. Robinson.

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Funding

This research was funded by the NIH (P60 AA011605, Project no. 3), the UNC Bowles Center for Alcohol Studies, R37 AA011852 and R01 AA014874. SCT was supported on a Summer Undergraduate Research Fellowship from UNC Chapel Hill. SJS was supported on 5P60AA011605-17S1 and JMD was supported on T32 AA007471.

Conflict of interest

The authors declare that they have no competing conflict of interest.

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Shnitko, T.A., Taylor, S.C., Stringfield, S.J. et al. Acute phenylalanine/tyrosine depletion of phasic dopamine in the rat brain. Psychopharmacology 233, 2045–2054 (2016). https://doi.org/10.1007/s00213-016-4259-0

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  • DOI: https://doi.org/10.1007/s00213-016-4259-0

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