Brain connectivity changes to fast versus slow dopamine increases

• Published in: Neuropsychopharmacology (New York, N.Y.) N.Y.), 2024-05, Vol.49 (6), p.924-932
• Main Authors: Manza, Peter, Tomasi, Dardo, Vines, Leah, Sotelo, Diana, Yonga, Michele-Vera, Wang, Gene-Jack, Volkow, Nora D
• Format: Article
• Language: English
• Subjects: Adult; Brain - diagnostic imaging; Brain - drug effects; Brain - metabolism; Brain Mapping; Brain stem; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - pharmacology; Cortex (parietal); Dopamine; Dopamine - metabolism; Dopamine Antagonists - administration & dosage; Dopamine Antagonists - pharmacology; Dopamine D1 receptors; Double-Blind Method; Female; Functional magnetic resonance imaging; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Methylphenidate; Methylphenidate - administration & dosage; Methylphenidate - pharmacology; Neostriatum; Neural networks; Neural Pathways - diagnostic imaging; Neural Pathways - drug effects; Positron-Emission Tomography; Prefrontal cortex; Raclopride; Raclopride - pharmacology; Receptors, Dopamine D1 - metabolism; Young Adult
• ISSN: 0893-133X; 1740-634X; 1740-634X
• DOI: 10.1038/s41386-024-01803-8

The rewarding effects of stimulant drugs such as methylphenidate (MP) depend crucially on how fast they raise dopamine in the brain. Yet how the rate of drug-induced dopamine increases impacts brain network communication remains unresolved. We manipulated route of MP administration to generate fast versus slow dopamine increases. We hypothesized that fast versus slow dopamine increases would result in a differential pattern of global brain connectivity (GBC) in association with regional levels of dopamine D1 receptors, which are critical for drug reward. Twenty healthy adults received MP intravenously (0.5 mg/kg; fast dopamine increases) and orally (60 mg; slow dopamine increases) during simultaneous [ C]raclopride PET-fMRI scans (double-blind, placebo-controlled). We tested how GBC was temporally associated with slow and fast dopamine increases on a minute-to-minute basis. Connectivity patterns were strikingly different for slow versus fast dopamine increases, and whole-brain spatial patterns were negatively correlated with one another (rho = -0.54, p