Gray-matter volume, midbrain dopamine D2/D3 receptors and drug craving in methamphetamine users

• Published in: Molecular psychiatry Vol. 20; no. 6; pp. 764 - 771
• Main Authors: Morales, A M, Kohno, M, Robertson, C L, Dean, A C, Mandelkern, M A, London, E D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2015; Nature Publishing Group
• Subjects: 59/57; 59/78; 631/378; 692/699/476/5; Addictions; Amphetamines; Amygdala; Behavioral Sciences; Benzamides - pharmacokinetics; Biological Psychology; Brain; Care and treatment; Cerebellum; Dopamine; Dopamine Antagonists - pharmacokinetics; Dopamine D2 receptors; Dopamine D3 receptors; Dopamine receptors; Drug abuse; Drug addiction; Drug-Seeking Behavior - physiology; Female; Fluorodeoxyglucose F18 - pharmacokinetics; Gray Matter - drug effects; Gray Matter - pathology; Health aspects; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Mesencephalon; Mesencephalon - diagnostic imaging; Mesencephalon - drug effects; Mesencephalon - pathology; Methamphetamine; Methamphetamine - pharmacology; Neostriatum; Neuroimaging; Neurosciences; Neurotoxicity; Occipital lobe; original-article; PET imaging; Pharmacists; Pharmacotherapy; Positron emission tomography; Prefrontal cortex; Protein Binding - drug effects; Psychiatry; Receptors, Dopamine D2 - metabolism; Regression Analysis; Self report; Substance-Related Disorders - pathology; Substance-Related Disorders - physiopathology; Substance-Related Disorders - psychology; Temporal lobe; Thalamus; Time Factors; Tomography; California; Los Angeles California; United States > US
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2015.47

Dysfunction of the mesocorticolimbic system has a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [ 18 F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BP nd ) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported drug craving were examined. Although no difference in midbrain D2/D3 BP nd was detected between methamphetamine and control groups, midbrain D2/D3 BP nd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BP nd interaction, P <0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum and thalamus ( P <0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BP nd and methamphetamine craving was not detected. Lower midbrain D2/D3 BP nd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BP nd , may be important for understanding the basis of drug craving, a key factor in the maintenance of substance-use disorders.