Neuropsychopharmacology 2004 Feb;29(2):427-32
Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Acute phenylalanine/tyrosine depletion (APTD) has been proposed as a new method to decrease catecholamine neurotransmission safely, rapidly, and transiently. Validation studies in animals are encouraging, but direct evidence in human brain is lacking. In the present study, we tested the hypothesis that APTD would reduce stimulated dopamine (DA) release, as assessed by positron emission tomography (PET) and changes in [(11)C]raclopride binding potential (BP), a measure of DA D2/D3 receptor availability. Eight healthy men received two PET scans, both following d-amphetamine, 0.3 mg/kg, p.o., an oral dose known to decrease [(11)C]raclopride BP in ventral striatum. On the morning before each scan, subjects ingested, in counter-balanced order, an amino-acid mixture deficient in the catecholamine precursors, phenylalanine, and tyrosine, or a nutritionally balanced mixture. Brain parametric images were generated by calculating [(11)C]raclopride BP at each voxel. BP values were extracted from the t-map (threshold: t=4.2, equivalent to p<0.05, Bonferroni corrected) and a priori identified regions of interest from each individual’s coregistered magnetic resonance images. Both receptor parametric mapping and region of interest analyses indicated that [(11)C]raclopride binding was significantly different on the two test days in the ventral striatum (peak t=6.31; x=-25, y=-8, and z=0.1). In the t-map defined cluster, [(11)C]raclopride BP values were 11.8+/-11.9% higher during the APTD session (p<0.05). The reduction in d-amphetamine-induced DA release exhibited a linear association with the reduction in plasma tyrosine levels (r=-0.82, p<0.05). Together, the results provide the first direct evidence that APTD decreases stimulated DA release in human brain. APTD may be a suitable new tool for human neuropsychopharmacology research.
- On 1/4/05 3:54 AM, DrCBlum@aol.com wrote:
- Dear Dr. Leyton,
- I read the abstract of your article with great interest. I have a close friend and patient who has recently been diagnosed with Parkinson’s. While treatment with Levodopa is likely in the future, the hope of delaying this therapy is a desirable alternative. I have had a few patients who successfully treated their resting tremors with L Tyrosine supplementation. Do you think there is any reason to assume that a patient with early onset Parkinson’s might benefit from L Tyrosine and or L Phenylalanine supplementation?Any suggestions you might have to offer would be greatly appreciated.
- Subj: Re: Tyrosine and Dopamine Production
- Date: 1/4/2005 8:42:02 AM Eastern Standard Time
- From: Marco Leyton<firstname.lastname@example.org>
- Dear Dr. Blum,
- The administration of tyrosine supplements can increase dopamine release in the striatum in rats (eg, During et al 1988; Tam et al 1990), and the same effect could be expected in humans. There are also reports that tyrosine can improve coping with stressful situations (eg, Banderet and Lieberman, 1989) and facilitate abstinence in opiate- and alcohol-dependent patients (Chen et al. 2004). I am not aware, though, of any clinical trials testing the efficacy of tyrosine supplementation in Parkinson’s Disease.Beyond that, I wish your friend and patient the very best. Please note that I am neither a physician nor a neurologist, and so my comments above should be considered information rather than treatment advice. A neurologist, of course, would be best positioned to advise whether a brief trial of tyrosine supplements would be worth trying.
- Best regards,
- Banderet LE, Lieberman HR (1989): Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull 22:759-762
- Chen, T. J. H., Blum, K., Payte, J. T., Schoolfield, J., Hopper, D., Stanford, M., Braverman, E. R. (2004). Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy. Medical Hypotheses 63, 538-548
- During MJ, Acworth IN, Wurtman RJ (1988): Effects of systemic L-tyrosine on dopamine release from rat corpus striatum and nucleus accumbens. Brain Res 452:378-380
- Tam SY, Elsworth JD, Bradberry CW, Roth RH (1990): Mesocortical dopamine neurons: high basal firing frequency predicts tyrosine dependence of dopamine synthesis. J Neural Transm 81:97-110
- Marco Leyton, Ph.D.
- Assistant Professor
- Department of Psychiatry
- Department of Neurology & Neurosurgery
- McGill University
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