Skip to main content Accessibility help
×
Home

Antidopaminergic effects of dietary tyrosine depletion in healthy subjects and patients with manic illness

  • S. F. B. McTavish (a1), M. H. McPherson (a1), C. J. Harmer (a1), L. Clark (a1), T. Sharp (a2), G. M. Goodwin (a1) and P. J. Cowen (a1)...

Abstract

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.

Aims

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.

Method

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.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Antidopaminergic effects of dietary tyrosine depletion in healthy subjects and patients with manic illness
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Antidopaminergic effects of dietary tyrosine depletion in healthy subjects and patients with manic illness
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Antidopaminergic effects of dietary tyrosine depletion in healthy subjects and patients with manic illness
      Available formats
      ×

Copyright

Corresponding author

Dr S. F. B. McTavish, Neurosciences Building, Warneford Hospital, Oxford OX3 7JX, UK. Tel: 01865 223612; Fax: 01865 251076; e-mail: sarah.mctavish@psychiatry.oxford.ac.uk

Footnotes

Hide All

Declaration of interest

The study was supported by a grant from the Wellcome Trust to M. H. M. M. H. M. was a Nuffield Research Fellow, S. F. B. M. was an MRC Clinical Training Fellow and P. J. C. and T. S. are MRC Clinical Scientists.

Footnotes

References

Hide All
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM–IV). Washington, DC: APA.
Beigel, A., Murphy, D. L. & Bunney, W. E. (1971) The manic-state rating scale: scale construction, reliability and validity. Archives of General Psychiatry, 25, 256262.
Biggio, G., Porceddu, M. L. & Gessa, G. L. (1976) Decrease of homovanillic, dihydroxyphenylacetic acid and cyclic-adenosine-3′, 5′-monophosphate content by the acute administration of an amino acid mixture lacking tyrosine and phenylalanine. Journal of Neurochemistry, 26, 12531255.
Checkley, S. A. (1980) Neuroendocrine tests of monoamine function in man: a review of basic theory and its application to the study of depressive illness. Psychological Medicine, 10, 3553.
Chou, J. C., Zito, J. M., Vitrai, J., et al (1996) Neuroleptics in acute mania: a pharmacoepidemiological study. Annals of Pharmacotherapy, 30, 13961398.
Cole, B. J. & Robbins, T. W. (1992) Forebrain norepinephrine: role in controlled information processing in the rat. Neuropsychopharrnacology, 7, 129142.
Delgado, P. L., Charney, D. S., Price, L. H., et al (1990) Serotonin function and the mechanism of antidepressant action: reversal of antidepressantinduced remission by rapid depletion of plasma tryptophan. Archives of General Psychiatry, 47, 411418.
Furst, P., Pollack, T. A., Graser, H., et al (1990) Appraisal of four pre-column derivatization methods for the high-performance liquid chromatographic determination of free amino acids in biological materials. Journal of Chromatography, 499, 557569.
Harmer, C. J., McTavish, S. F. B., Clark, L., et al (2001) Tyrosine depletion attenuates dopamine function in healthy volunteers. Psychopharmacology, 154, 105111.
Hoebel, B. G., Hernandez, L., Schwartz, D. H., et al (1989) Microdialysis studies of brain norepinephrine, serotonin and dopamine release during ingestive behaviour. Annals of the New York Academy of Sciences, 575, 171191.
Jacobs, D. & Silverstone, T. (1986) Dextroamphetamine-induced arousal in human subjects as a model for mania. Psychological Medicine, 16, 323329.
Kapur, S., Zipursky, R., Jones, C., et al (2000) Relationship between dopamine D2 occupancy, clinical response, and side-effects: a double-blind PET study of first episode schizophrenia. American Journal of Psychiatry, 157, 514520.
Koelega, H. S. (1993) Stimulant drugs and vigilance performance: a review. Psychopharmacology, 111, 116.
Laruelle, M. (1998) Imaging dopamine neurotransmission in schizophrenia: a review and meta-analysis. Quarterly Journal of Nuclear Medicine, 42, 211221.
McTavish, S. F. B., Cowen, P. J. & Sharp, T. (1999) Effect of a tyrosine-free amino acid mixture on regional brain catecholamine synthesis and release. Psychopharmacology, 141, 182188.
McTavish, S. F. B., McPherson, M. H., Sharp, T., et al (1999) Attenuation of some subjective effects of amphetamine following tyrosine depletion. Journal of Psychopharmacology, 13, 144147.
Pardridge, W. M. (1977) Kinetics of competitive inhibition of neutral amino acid transport across the blood brain barrier. Journal of Neurochemistry, 28, 103108.
Pilla, M., Perachon, S., Sautel, F., et al (1999) Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. Nature, 400, 371375.
Robbins, T. W., James, T., Owen, A. M., et al (1994) CANTAB: a factor analytic study of a large sample of normal elderly volunteers. Dementia, 5, 266281.
Sharp, T., Zetterstrom, T., Ljundberg, T., et al (1987) A direct comparison of amphetamine-induced behaviours and regional brain dopamine release in the rat using intracerebral dialysis. Brain Research, 401, 322330.
Sheehan, B. D., Tharyan, P., McTavish, S. F. B., et al (1996) Use of a dietary manipulation to deplete plasma tyrosine and phenylalanine in healthy subjects. Journal of Psychopharmacology, 10, 231234.
Silverstone, T. (1983) The clinical pharmacology of appetite – its relevance to psychiatry. Psychological Medicine, 13, 251253.
Smith, K. A., Fairburn, C. G. & Cowen, P. J. (1997) Relapse of depression after rapid depletion of tryptophan. Lancet, 349, 915919.
Wurtman, R. J., Hefti, F. & Melamed, E. (1981) Precursor control of neurotransmitter synthesis. Pharmacological Reviews, 10, 315335.
Young, R. C., Biggs, J. T., Ziegler, V. E., et al (1978) A rating scale for mania: reliability, validity and sensitivity. British Journal of Psychiatry, 133, 429435.

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Antidopaminergic effects of dietary tyrosine depletion in healthy subjects and patients with manic illness

  • S. F. B. McTavish (a1), M. H. McPherson (a1), C. J. Harmer (a1), L. Clark (a1), T. Sharp (a2), G. M. Goodwin (a1) and P. J. Cowen (a1)...
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *