Department of Chemistry and Biochemistry, The University of South Carolina, Columbia, SC, USA.
Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina SOM, Columbia, SC, USA.
Handb Exp Pharmacol. 2021;266:101-117. doi: 10.1007/164_2021_452.
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.
神经调节剂是大脑信号过程的关键调节剂，因此它们是精神活性治疗的热门药理学靶点。很明显，单胺摄取机制很复杂，受多种摄取机制的影响。摄取 1 描述了通过其指定转运体（5-羟色胺转运体[SERT]、去甲肾上腺素转运体[NET]和多巴胺转运体[DAT]）摄取单胺，而摄取 2 详细说明了神经元和神经胶质上的多种转运体类型摄取不同类型的调节剂，不一定特定于单胺。虽然过去几十年来对摄取 1 过程进行了深入研究，但由于方法的局限性，摄取 2 机制仍然更难研究，这些方法的灵敏度和时空分辨率不足以观察摄取谱的细微差别。在本章中，我们回顾了不同的实验方法，这些方法提供了关于体内摄取 2 机制的重要信息。详细描述了这些技术（闪烁微分光光度法、微透析、恒电流安培法和伏安法），并突出了与每种方法相关的关键研究。从这些综述中可以清楚地看出，摄取 2 过程对于深入了解大脑和开发有效的神经精神治疗方法至关重要。
