Peter Manza
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Health
The addictiveness of stimulant drugs such as methylphenidate (MP) depends crucially on how fast they raise dopamine in the brain. Yet the brain circuits underlying the rate dependency to drug reward have not been resolved. We used simultaneous PET-fMRI to link dynamic changes in brain dopamine signaling, functional brain activity/connectivity, and the self-reported experience of ‘high’ in 20 healthy adults receiving MP at different speeds: slow (oral 60mg) and fast (intravenous-IV 0.25mg/kg) doses in a double-blind, counterbalanced, placebo-controlled study. We estimated speed of striatal dopamine increases to oral and IV MP and then tested where brain activity/connectivity was associated with slow and fast dopamine kinetics. The two administrations produced dramatically different effects on brain functional activation and connectivity despite a comparable overall magnitude of dopamine increases. These data demonstrate how fast dopamine increases generate unique effects on brain function that have relevance for the addictive potential of drugs.
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