The American Journal of Psychiatry

Published Online:

LIEUWE de HAAN , M.D., Ph.D., JAN BOOIJ , M.D., Ph.D.,JULES LAVALYE , M.D., Ph.D.,T. van AMELSVOORT , M.D., Ph.D., andDON LINSZEN , M.D., Ph.D., Amsterdam, the Netherlands

A paradigm that induces acute dopamine depletion with the drug alphamethylpara tyrosine (AMPT), a reversible inhibitor of tyrosine hydroxylase, has been used successfully to assess the occupancy of striatal dopamine D2 receptors by endogenous dopamine in vivo (1). Here we describe the dramatic subjective experiences induced by acute dopamine depletion in one healthy volunteer. They included a whole spectrum of psychiatric symptoms and highlighted the contribution of the dopaminergic system to diverse major psychiatric disorders.

In our study, dopamine depletion was achieved by oral administration of 4.5 g AMPT in 25 hours, as described earlier (1). Striatal D2 receptors were assessed at baseline and after acute dopamine depletion by using the bolus/constant infusion [123I]IBZM technique (1). Acquisition, reconstruction, and analysis of the single photon emission computed tomography data were performed as described previously (2).

Mr. A was a healthy, extraverted, very well functioning 21-year-old medical student without even minor psychological difficulties or psychiatric disorders in his family. His Global Assessment of Functioning Scale score was 97. Written informed consent was obtained from Mr. A. We will describe the spontaneous reported subjective experiences after he started the first dose of 750 mg AMPT at t=0 hours (1).

After 7 hours, Mr. A felt more distance between himself and his environment. Stimuli had less impact; visual and audible stimuli were less sharp. He experienced a loss of motivation and tiredness. After 18 hours, he had difficulty waking up and increasing tiredness; environmental stimuli seemed dull. He had less fluency of speech. After 20 hours, he felt confused. He felt tense before his appointment and had an urge to check his watch in an obsessive way.

After 24 hours, Mr. A had inner restlessness, flight of ideas; his ideas seemed inflicted, and he could not remember them. He felt a loss of control over his ideas. After 28 hours, he felt ashamed, frightened, anxious, and depressed. He was afraid that the situation would continue. At that time, blepharospasm, mask face, and tremor were noted. After 30 hours, he was tired and slept 11 hours. After 42 hours, he had poor concentration. In the next hours, he returned to normal.

The striatal-to-nonspecific binding ratio was 27% higher after Mr. A took AMPT compared to the baseline situation, indicating severe acute dopamine depletion (1).

During increasing dopamine depletion in this case, a range of subjective experiences appeared and disappeared consecutively. These experiences resembled negative symptoms, obsessive-compulsive symptoms, thought disorders, and anxiety and depressive symptoms and highlight the importance of the role of dopamine in major psychiatric disorders. In former studies, AMPT was found to lower mood, induce fatigue, decrease subjective alertness, and/or induce extrapyramidal symptoms in some healthy individuals (reviewed in reference 3).

Since the subjective experiences due to acute dopamine depletion could be dramatic, we believe that subjects participating in dopamine-depletion studies should be well informed about possible temporarily—but intense—side effects.


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2. Booij J, Korn P, Linszen DH, van Royen EA: Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography. Eur J Nucl Med 1997; 24:674–677MedlineGoogle Scholar

3. Booij L, Van der Does AJ, Riedel WJ: Monoamine depletion in psychiatric and healthy populations. Mol Psychiatry 2003; 8:951–973Crossref, MedlineGoogle Scholar