Tyrosine depletion attenuates dopamine function in healthy volunteers
Abstract
Rationale Tyrosine depletion has been shown to reduce dopamine over activity in animal and human investigations. However, the effects on basal dopamine function have not been explored. Such information could establish tyrosine depletion as an effective probe of dopamine function in healthy volunteers and would also have relevance for future therapeutic applications of this manipulation.Objective The present study investigated the effect of acute tyrosine depletion on dopamine function in healthy volunteers using a combination of neuroendocrine, neuropsychological and subjective measures.Methods On one occasion, volunteers received an amino acid drink selectively lacking tyrosine and phenylalanine (TYR-free), whilst on the other they received a balanced (BAL) amino acid drink. Plasma prolactin, amino acid levels and subjective state were monitored over 6 h following the two drinks, and volunteers also completed a battery of tests from the CANTAB, including measures of spatial memory previously found to be sensitive to changes in dopamine function.Results Plasma prolactin levels rose following the TYR-free drink relative to the balanced mixture, indicative of decreased dopamine neurotransmission within the hypothalamus. Following the TYR-free drink, volunteers were impaired at spatial recognition memory and spatial working memory. Volunteers also tended to report that they felt less good following the TYR-free than the BAL mixture.Conclusion Tyrosine depletion in healthy volunteers affected baseline dopamine function on the different measures employed in this study. Tyrosine depletion would thereby seem valuable as a probe of dopamine function in human volunteers. Ratings of depression and other aspects of cognitive function were unaffected, suggesting that this manipulation may be free of significant side effects when used as a treatment for conditions characterised by dopamine over activity, such as acute mania and schizophrenia.
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Tyrosine depletion experiments suggest that acute reductions in brain catecholamine levels lead people to behave in a less motivated way or to develop cognitive impairments.
“In line with this, tyrosine depletion experiments, in which participants consume an amino acid mixture devoid of tyrosine and its precursor, phenylalanine, suggest that acute reductions in brain catecholamine levels lead people to behave in a less motivated way (McLean et al., 2004;Roiser et al., 2005;Cawley et al., 2013) or develop cognitive impairments (Harmer et al., 2001).”
From Behavioral and cognitive effects of tyrosine intake in healthy human adults (2015) · cites this paper as Harmer et al., 2001
The release of prolactin from the anterior pituitary is inhibited by dopamine in the brain.
“This was unexpected because the release of prolactin from the anterior pituitary is inhibited, rather than stimulated, by dopamine in the brain (Strüder et al., 1998;Harmer et al., 2001).”
From Behavioral and cognitive effects of tyrosine intake in healthy human adults (2015) · cites this paper as Harmer et al., 2001
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Hughes, J.-M., Matrenza, C., Kemp, A. H., Harrison, B. J., Liley, D., & Nathan, P. J. (2004) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145703003845 · Cited by 16 · see citing works
Neuroscience of Drugs and Addiction
Robbins, T. W., Cardinal, R. N., Ciano, P. D., Halligan, P. W., Hellemans, K., Lee, J. L. C., & Everitt, B. J. (2007) · Elsevier eBooks · doi:10.1016/b978-012370624-9/50006-2 · Cited by 16 · see citing works
Jorissen, B. L., & Riedel, W. J. (2002) · Clinical Nutrition · doi:10.1054/clnu.2001.0510 · Cited by 16 · see citing works
- Authors
- Harmer, C. J., McTavish, S. F. B., Clark, L., Goodwin, G. M., & Cowen, P. J.
- Affiliations
- Warneford Hospital (GB)
- Venue
- Psychopharmacology
- Published
- 2001-02-22
- Volume
- 154
- Issue
- 1
- Pages
- 105-111
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2094484291
- Cited by
- 158
- References
- 0
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 8 · 2015: 9 · 2014: 3 · 2013: 14 · 2012: 5
- FWCI
- 3.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- dopaminergic activity, prolactin, amino acid restriction, spatial memory, working memory, subjective well-being, hypothalamic dopamine, mania, schizophrenia, healthy volunteers
- MeSH terms
- Adult, Cognition, Dopamine, Female, Humans, Male, Mental Processes, Neuropsychological Tests, Paired-Associate Learning, Pattern Recognition, Visual, Prolactin, Tyrosine, Visual Perception, Cross-Over Studies
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