Midbrain Functional Connectivity and Ventral Striatal Dopamine D2-type Receptors: Link to Impulsivity in Methamphetamine Users

HHS Public Access Author manuscript Author Manuscript Mol Psychiatry. Author manuscript; available in PMC 2016 August 10. Midbrain functional connectivity and ventral striatal dopamine D2-type receptors: Link to impulsivity in methamphetamine users Author Manuscript Milky Kohno, PhD 1 , Kyoji Okita, MD, PhD 1,5 , Angelica M. Morales, PhD 1 , Chelsea Robertson, PhD 1,2,5 , Andy C. Dean, PhD 1,3 , Dara G. Ghahremani, PhD 1 , Fred Sabb, PhD 1 , Mark A. Mandelkern, MD, PhD 4,6 , Robert M. Bilder, PhD 1,4 , and Edythe D. London, PhD 1,2,3,5 1 Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095 2 Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095 3 Brain Research Institute, University of California Los Angeles, Los Angeles, CA 90095 4 Department of Psychology, University of California Los Angeles, Los Angeles, CA 90095 5 Veterans Administration of Greater Los Angeles Healthcare System, University of California Irvine, Irvine, CA. 6 Department of Physics, University of California Irvine, Irvine, CA. Author Manuscript Abstract Author Manuscript 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 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 [ 18 F]fallypride positron emission tomography to measure ventral striatal dopamine D2-type receptor availability, indexed by binding potential (BP ND ), 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 BP ND interaction effect on RSFC, reflecting a negative relationship between ventral striatal BP ND and RSFC between midbrain and striatum, orbitofrontal cortex, and insula in methamphetamine-dependent participants but a positive Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Correspondence: Edythe D. London, Ph.D., elondon@mednet.ucla.edu, Address: UCLA Semel Institute, 740 Westwood Plaza, C8-831, Los Angeles, CA 90095, Phone: (310) 825-0606, Fax: (310) 825-0812. Disclosure/Conflict of Interest The investigators have no conflicts of interest or financial disclosures to report.