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Midbrain functional connectivity and ventral striatal dopamine D2-type receptors: link to impulsivity in methamphetamine users

Molecular Psychiatry volume 21, pages 1554–1560 (2016)Cite this article

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Abstract

Stimulant use disorders are associated with deficits in striatal dopamine receptor availability, abnormalities in mesocorticolimbic resting-state functional connectivity (RSFC) and impulsivity. In methamphetamine-dependent research participants, impulsivity is correlated negatively with striatal D2-type receptor availability, and mesocorticolimbic RSFC is stronger than that in controls. The extent to which these features of methamphetamine dependence are interrelated, however, is unknown. This question was addressed in two studies. In Study 1, 19 methamphetamine-dependent and 26 healthy control subjects underwent [18F]fallypride positron emission tomography to measure ventral striatal dopamine D2-type receptor availability, indexed by binding potential (BPND), and functional magnetic resonance imaging (fMRI) to assess mesocorticolimbic RSFC, using a midbrain seed. In Study 2, an independent sample of 20 methamphetamine-dependent and 18 control subjects completed the Barratt Impulsiveness Scale in addition to fMRI. Study 1 showed a significant group by ventral striatal BPND interaction effect on RSFC, reflecting a negative relationship between ventral striatal BPND and RSFC between the midbrain and striatum, orbitofrontal cortex and insula in methamphetamine-dependent participants, but a positive relationship in the control group. In Study 2, an interaction of the group with RSFC on impulsivity was observed. Methamphetamine-dependent users exhibited a positive relationship of midbrain RSFC to the left ventral striatum with cognitive impulsivity, whereas a negative relationship was observed in healthy controls. The results indicate that ventral striatal D2-type receptor signaling may affect the system-level activity within the mesocorticolimbic system, providing a functional link that may help explain high impulsivity in methamphetamine-dependent individuals.

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Acknowledgements

The research described here was funded in part by NIH grants P20 DA022539, R01 DA020726 (EDL), NIDA R01DA027633 (RAR), K23DA027734 (ACD), R21DA034928 (ACD), UL1TR000124 (UCLA CTSA), the Consortium for Neuropsychiatric Phenomics (NIH Roadmap for Medical Research grants UL1-DE019580 and RL1DA024853) and endowments from the Thomas P and Katherine P. Pike Chair in Addiction Studies, and the Marjorie Greene Trust.

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Authors and Affiliations

  1. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA

    M Kohno, K Okita, A M Morales, C L Robertson, A C Dean, D G Ghahremani, F W Sabb, R A Rawson, R M Bilder & E D London

  2. Veterans Administration of Greater Los Angeles Healthcare System, University of California Irvine, Irvine, CA, USA

    K Okita, C L Robertson & E D London

  3. Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA

    C L Robertson & E D London

  4. Brain Research Institute, University of California Los Angeles, Los Angeles, CA, USA

    A C Dean & E D London

  5. Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA

    M A Mandelkern & R M Bilder

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

    M A Mandelkern

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Kohno, M., Okita, K., Morales, A. et al. Midbrain functional connectivity and ventral striatal dopamine D2-type receptors: link to impulsivity in methamphetamine users. Mol Psychiatry 21, 1554–1560 (2016). https://doi.org/10.1038/mp.2015.223

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