Prefrontal cortex dopamine release measured in vivo with positron emission tomography: Implications for the stimulant paradigm

Experimental tasks and stimulant paradigms in combination with D-2/3 emission tomography have been essential in understanding the dopamine (DA) system. However, whereas task-induced DA release is dependent on a mechanism that is largely similar throughout the brain, the DA-increasing stimulant mechanism of action changes drastically from striatum to cortex. We posit the problems that may be encountered when translating the stimulant emission tomography paradigm from striatum to PFC. After comparing the available human data on task- and stimulant-induced changes in extracellular PFC DA assessed with PET, we hypothesize that the stimulant paradigm in the PFC, even with high affinity tracers, may not completely capture the true effect of stimulants on extracellular PFC DA levels. Task-induced and stimulant-induced effects on extracellular PFC DA measured with emission tomography should therefore be regarded as different phenomena. We conclude with future directions and alternative probes to measure PFC DA transmission with emission tomography.