0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letter to the Editor   |    
Subjective Experiences During Dopamine Depletion
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.; DON LINSZEN, M.D., Ph.D.
Am J Psychiatry 2005;162:1755-1755. doi:10.1176/appi.ajp.162.9.1755

To the Editor: 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.

Verhoeff NP, Kapur S, Hussey D, Lee M, Christensen B, Papatheodorou G, Zipursky RB: A simple method to measure baseline occupancy of neostriatal dopamine D2 receptors by dopamine in vivo in healthy subjects. Neuropsychopharmacology  2001; 25:213–223
[PubMed]
[CrossRef]
 
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; 24:674–677
[PubMed]
 
Booij L, Van der Does AJ, Riedel WJ: Monoamine depletion in psychiatric and healthy populations. Mol Psychiatry  2003; 8:951–973
[PubMed]
[CrossRef]
 
+

References

Verhoeff NP, Kapur S, Hussey D, Lee M, Christensen B, Papatheodorou G, Zipursky RB: A simple method to measure baseline occupancy of neostriatal dopamine D2 receptors by dopamine in vivo in healthy subjects. Neuropsychopharmacology  2001; 25:213–223
[PubMed]
[CrossRef]
 
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; 24:674–677
[PubMed]
 
Booij L, Van der Does AJ, Riedel WJ: Monoamine depletion in psychiatric and healthy populations. Mol Psychiatry  2003; 8:951–973
[PubMed]
[CrossRef]
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 12

Related Content
Books
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 9.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 4.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 5.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 14.  >
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition > Chapter 1.  >
Topic Collections
Psychiatric News
PubMed Articles