Experimental Methods for Investigating Uptake 2 Processes In Vivo

Neuromodulators are critical regulators of the brain's signaling processes, and thus they are popular pharmacological targets for psychoactive therapies. It is clear that monoamine uptake mechanisms are complicated and subject to multiple uptake mechanisms. Uptake 1 describes uptake of the monoamine via its designated transporter (SERT for serotonin, NET for norepinephrine, and DAT for dopamine), whereas Uptake 2 details multiple transporter types on neurons and glia taking up different types of modulators, not necessarily specific to the monoamine. While Uptake 1 processes have been well-studied over the past few decades, Uptake 2 mechanisms have remained more difficult to study because of the limitations in methods that have the sensitivity and spatiotemporal resolution to look at the subtleties in uptake profiles. In this chapter we review the different experimental approaches that have yielded important information about Uptake 2 mechanisms in vivo. The techniques (scintillation microspectrophotometry, microdialysis, chronoamperometry, and voltammetry) are described in detail, and pivotal studies associated with each method are highlighted. It is clear from these reviewed works that Uptake 2 processes are critical to consider to advance our understanding of the brain and develop effective neuropsychiatric therapies.