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

• Published in: Molecular psychiatry 2016-11, Vol.21 (11), p.1554-1560
• Main Authors: Kohno, M, Okita, K, Morales, A M, Robertson, C L, Dean, A C, Ghahremani, D G, Sabb, F W, Rawson, R A, Mandelkern, M A, Bilder, R M, London, E D
• Format: Article
• Language: English
• Subjects: 59/36; 59/78; 631/378; 631/477; Addictions; Addictive behaviors; Adult; Amphetamine-Related Disorders - metabolism; Behavior; Behavioral Sciences; Biological Psychology; Brain research; Central Nervous System Stimulants; Cognitive ability; Dopamine; Dopamine - metabolism; Dopamine D2 receptors; Drug abuse; Female; Functional magnetic resonance imaging; Humans; Impulsive behavior; Impulsive Behavior - drug effects; Impulsive Behavior - physiology; Impulsivity; Independent sample; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Mesencephalon; Mesencephalon - drug effects; Methamphetamine; Methamphetamine - adverse effects; Methamphetamine - metabolism; Middle Aged; Neostriatum; Neuroimaging; Neurosciences; original-article; Pharmacotherapy; Positron emission tomography; Positron-Emission Tomography - methods; Prefrontal Cortex - metabolism; Psychiatry; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D2 - physiology; Tomography; Ventral Striatum - drug effects; Ventral Striatum - physiopathology
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2015.223

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 [ 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 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.