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Comment
. 2000 Jul 5;97(14):7673-5.
doi: 10.1073/pnas.97.14.7673.

Schizophrenia: more dopamine, more D2 receptors

P Seeman  1 , S Kapur
Affiliations
Comment

Schizophrenia: more dopamine, more D2 receptors

P Seeman et al. Proc Natl Acad Sci U S A. .
No abstract available

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Figures

Figure 1
Figure 1
Method and findings of Abi-Dargham et al. (2) to reveal an increased occupancy of dopamine D2 receptors in schizophrenia. (Top) The number of dopamine D2 receptors, measured by the [123I]IBZM binding potential (green triangles with I), were the same in the brain striata of control and schizophrenia subjects. The levels of synaptic dopamine (pink triangles with D), which is higher in patients compared to control subjects, normally occupies most of the D2 receptors, masking the difference between control and schizophrenia individuals. (Bottom) After partial depletion of endogenous brain dopamine by oral ingestion of α-methylparatyrosine over 2 days, the binding of [123I]IBZM rose in both the control and schizophrenia subjects, but that for the patients rose significantly higher.
Figure 2
Figure 2
Possible model to account for the increased number of dopamine D2 receptors in schizophrenia seen with [11C]methylspiperone but not with [11C]raclopride. It is known that the photolabel of spiperone ([125I]azidophenethylspiperone) primarily or selectively labels monomers of D2 receptors, whereas the benzamide photolabel ([125I]azido-iodo-nemonapride) unselectively labels monomers, dimers, and oligomers of D2 receptors (see text). These findings suggest that even if there is no increase in the total population of D2 receptors in schizophrenia, an increase in the proportion of monomers caused by the increased level of dopamine in schizophrenia (see Fig. 1) would result in an increase in the binding of [11C]methylspiperone (red triangle with S) in schizophrenia but not with [11C]raclopride (white triangle with R).
See this image and copyright information in PMC

Comment on

  • Increased baseline occupancy of D2 receptors by dopamine in schizophrenia.
    Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, Van Heertum RL, Gorman JM, Laruelle M. Abi-Dargham A, et al. Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8104-9. doi: 10.1073/pnas.97.14.8104. Proc Natl Acad Sci U S A. 2000. PMID: 10884434 Free PMC article.

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    1. Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles L S, Weiss R, Cooper T B, Mann J J, Van Heertum R L, et al. Proc Natl Acad Sci USA. 2000;97:8104–8109. - PMC - PubMed
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