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Acute D2 receptor blockade induces rapid, reversible remodeling in human cortical-striatal circuits

Abstract

Structural remodeling has been observed in the human brain over periods of weeks to months, but the molecular mechanisms governing this process remain incompletely characterized. Using multimodal pharmaco-neuroimaging, we found that acute D2 receptor blockade induced reversible striatal volume changes and structural-functional decoupling in motor circuits within hours; these alterations predicted acute extrapyramidal motor symptoms with high precision. Our findings suggest a role for D2 receptors in short-term neural plasticity and identify a potential biomarker for neuroleptic side effects in humans.

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Figure 1: Neuroleptic-induced changes in brain structure, brain function and motor control.
Figure 2: Neuroleptic-induced changes in structural coupling of the cortical-striatal motor circuitry.

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Acknowledgements

We thank A. Tenckhoff, J. Rauschenberg, A. Schmitt, M. Hoerst and I. Wolf for research assistance. This research was supported in part by the Intramural Research Program of the National Institute of Mental Health, the US National Institutes of Health and a Deutsche Forschungsgemeinschaft–National Institutes of Health scholarship grant to H.T. (To 539/1-1).

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H.T., D.F.B. and F.H. designed the study. H.T., D.F.B., M.R., C.V. and F.H. conducted the experiments. H.T., S.H. and A.M.-L. performed the data analyses and wrote the manuscript. A.M.-L. supervised the project.

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Correspondence to Heike Tost.

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The authors declare no competing financial interests.

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Supplementary Figures 1–3, Supplementary Tables 1 and 2, Supplementary Methods, Supplementary Results and Supplementary Discussion (PDF 844 kb)

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Tost, H., Braus, D., Hakimi, S. et al. Acute D2 receptor blockade induces rapid, reversible remodeling in human cortical-striatal circuits. Nat Neurosci 13, 920–922 (2010). https://doi.org/10.1038/nn.2572

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