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Striatal dopamine D1-type receptor availability: no difference from control but association with cortical thickness in methamphetamine users

Molecular Psychiatry volume 23, pages 1320–1327 (2018)Cite this article

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Abstract

Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted only on post-mortem material, with no differences in methamphetamine users from controls in the caudate nucleus and putamen and higher D1-receptor density in the nucleus accumbens. Released from neurons when methamphetamine is self-administered, dopamine binds to both D1- and D2-type receptors in the striatum, with downstream effects on cortical activity. Thus, both receptor subtypes may contribute to methamphetamine-induced alterations in cortical morphology and behavior. In this study, 21 methamphetamine-dependent subjects and 23 healthy controls participated in positron emission tomography and structural magnetic resonance imaging for assessment of striatal D1- and D2-type receptor availability and cortical gray-matter thickness, respectively. Although D2-type receptor availability (BPnd) was lower in the methamphetamine group, as shown previously, the groups did not differ in D1-type BPnd. In the methamphetamine group, mean cortical gray-matter thickness was negatively associated with cumulative methamphetamine use and craving for the drug. Striatal D1-type but not D2-type BPnd was negatively associated with global mean cortical gray-matter thickness in the methamphetamine group, but no association was found between gray-matter thickness and BPnd for either dopamine receptor subtype in the control group. These results suggest a role of striatal D1-type receptors in cortical adaptation to chronic methamphetamine use.

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Acknowledgements

This research was supported, in part, by grants from the National Institute on Drug Abuse (K23 DA027734 and R21 DA034928, ACD) and endowments from the Thomas P and Katherine K Pike Chair in Addiction Studies (EDL) and the Marjorie M Greene Trust. KO was partly supported by Department of Psychiatry, Graduate School of Medicine, Chiba University, DOMONKAI fund. We acknowledge the excellent technical support provided by Karen Lazare, Josephine Ribe and Garrett Crook in PET acquisition, and Bryan Garrison and Dmitriy Gekker in radioligand preparation.

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  1. Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA

    K Okita, A M Morales, A C Dean, M C Johnson & E D London

  2. Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA

    K Okita, J Farahi, M A Mandelkern & E D London

  3. Brain Research Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA

    A C Dean & E D London

  4. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA

    V Lu & E D London

  5. Department of Physics, University of California Irvine, Irvine, CA, USA

    M A Mandelkern

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Okita, K., Morales, A., Dean, A. et al. Striatal dopamine D1-type receptor availability: no difference from control but association with cortical thickness in methamphetamine users. Mol Psychiatry 23, 1320–1327 (2018). https://doi.org/10.1038/mp.2017.172

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