Abstract
AbstractPositron Emission Tomography (PET) and Single Photon Emission Computerized Tomography (SPECT) imaging can be applied to measure acute fluctuations in endogenous dopamine (DA) in the living human brain, as captured by opposite changes in D2 receptor ligand in vivo binding. This application of neuroreceptor imaging provides a dynamic assessment of neurotransmission that is very informative to our understanding of the role of DA in health and disease. This chapter reviews briefly the imaging results of endogenous competition studies at D2 receptors obtained in nonhuman primates, healthy subjects, and subjects with neuropsychiatric conditions. This review is followed by a discussion of nature and properties of the interactive processes between DA and D2 receptor binding agents that enable this imaging technique. The original occupancy model proposed that changes in radiotracer binding potential (BP) are directly caused by changes in occupancy of D2 receptors by DA and by classical binding competition. A number of experimental data support this model. The evidence that manipulation of DA synaptic levels induce change in the binding potential (BP) of most D2 radiotracers (antagonists and agonists), irrespective of their affinity, is unequivocal. The fact that these changes in BP are mediated by changes in DA synaptic concentration is well documented. The quantitative relationship between changes in extracellular DA and changes in BP has been established. The observation that the in vivo binding of radiolabeled agonists is more vulnerable than that of antagonists to changes in endogenous DA also support the occupancy model. On the other hand, the amphetamine-induced changes in the BP of D2 receptor supports last longer than amphetamine-induced changes in DA extracellular concentration and that the behavioral and physiological effects of amphetamine. Recent data strongly suggest that DA mediated internalization of D2 receptors is involved in the late phase of the radioligands BP reduction. A general model is proposed, in which the early reduction in BP is caused by binding competition, while the later phase is due to decrease affinity of D2 receptor radiotracers to internalized D2 receptors.Key wordsPET, SPECTDopamineRacloprideIBZMFallyprideFLB 457NPAMNPAPHNOSpiperoneInternalization
Published Version
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