Abstract
The mesocorticolimbic dopamine (DA) circuit, comprising the mesolimbic and mesocortical DA pathways, plays a crucial role in reward, cognitive control, and motivation. The positron emission tomography (PET) radiotracer, [C-11]raclopride, has been used widely to image DA receptors and DA changes in the mesolimbic pathway before and after pharmacological and behavioral challenges. In certain circumstances, properties of traditional kinetic models—used to analyze dynamic PET data—are not well-suited to describing the effects of stimulus-induced DA release. To combat model shortcomings, the authors have advanced a suite of models that characterizes PET data in the presence of time-varying DA release. We review select [C-11]raclopride studies of the striatum during cigarette smoking to illustrate the advantages of such models. DA receptors occur in lower density in the cortex than the striatum. This, as well as higher relative background signal, poses a serious challenge to quantitative PET of DA changes in the mesocortical system. Novel high affinity radioligands [F-18]fallypride and [C-11]FLB457 have been used to image mesocortical DA transmission. Models with time-varying terms may also hold the key to optimizing sensitivity to changes in mesocortical DA. As an illustration, we compare recent PET studies of the effect of stress on cortical DA release. Finally, we consider some challenges and strategies for further optimization of sensitivity of PET to stimulus-induced DA changes throughout the whole brain.
Highlights
Dopamine (DA) is an essential neurotransmitter for every-day brain functions including experiencing pleasure, regulating attention, and learning to control urges
The mesocortical DA pathway originates in the ventral tegmental area (VTA), but produces DA release in the prefrontal cortex (PFC) (Swanson 1982)
The mesolimbic pathway is critical for reinforcing motivated behavior, whereas the mesocortical pathway underlies emotional response and cognitive control, such as learning to inhibit drug use (Salamone and Correa 2002; Berridge 2007; Robinson and Berridge 1993; Schultz 2007; Dichter, Damiano, and Allen 2012)
Summary
Dopamine (DA) is an essential neurotransmitter for every-day brain functions including experiencing pleasure, regulating attention, and learning to control urges. Microdialysis and [C-11]FLB457 PET have been used together to examine DA transmission in the cortex of monkeys, leading to claims that DA transmission may be slow (“therapeutic”) in the cortex and fast (“addictive”) in the striatum (Jedema et al 2014) These distinctions would be consistent with postulated functions of the mesolimbic and mesocortical systems, respectively. The papers help to illustrate the need for sophisticated modeling to properly detect and quantify the contribution of the DA signal to the PET data These studies and further methodological refinements can lay the foundation for detailed characterization of both the mesolimbic and mesocortical DA loops. The investigators recorded a 26–37% drop in BPND (increase in DA) from before to after the smoking break in those who smoked They employed apparently identical scanning and analysis procedures in the two follow-up studies. What could be at the root of such an inconsistency?
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
