Techniques for Measurement of Serotonin: Implications in Neuropsychiatric Disorders and Advances in Absolute Value Recording Methods

Abstract

Serotonin (5-HT) is a monoamine neurotransmitter in the peripheral, enteric, and central nervous systems (CNS). Within the CNS, serotonin is principally involved in mood regulation and reward-seeking behaviors. It is a critical regulator in CNS pathologies such as major depressive disorder, addiction, and schizophrenia. Consequently, in vivo serotonin measurements within the CNS have emerged as one of many promising approaches to investigating the pathogenesis, progression, and treatment of these and other neuropsychiatric conditions. These techniques vary in methods, ranging from analyte sampling with microdialysis to voltammetry. Provided this diversity in approach, inherent differences between techniques are inevitable. These include biosensor size, temporal/spatial resolution, and absolute value measurement capabilities, all of which must be considered to fit the prospective researcher's needs. In this review, we summarize currently available methods for the measurement of serotonin, including novel voltammetric absolute value measurement techniques. We also detail serotonin's role in various neuropsychiatric conditions, highlighting the role of phasic and tonic serotonergic neuronal firing within each where relevant. Lastly, we briefly review the present clinical application of these techniques and discuss the potential of a closed-loop monitoring and neuromodulation system utilizing deep brain stimulation (DBS).

Keywords: FSCAV; FSCV; MDD; N-MCSWV; Serotonin; addiction; depression; electrochemistry; opioids; schizophrenia.

Figure 1

Schematic of the waveform utilized in N-MCSWV and depiction of dynamic background subtraction (A, B). A voltammogram with serotonin’s oxidation and reduction is depicted as a color plot (C). Reprinted (adapted) with permission from Hojin Shin, Abhinav Goyal, et al. Analytical Chemistry 202193 ( (51), ), 16987–16994 . Copyright 2021 American Chemical Society.

Figure 2

In vivo (Ai) and in vitro (Aii) FSCAV color plots. Black bars indicate the 10 s controlled adsorption period. Cyclic voltammograms captured at 100 Hz for detection of the adsorbed molecule, serotonin, are colored red (B). The voltammogram captured at 100 Hz in vitro and in vivo is indicated by the dotted and solid lines, respectively. The inset in panel B shows the serotonin concentration measurements obtained from the mouse hippocampal CA2 region (n = 15). Reprinted (adapted) with permission from Aya Abdalla, Christopher W. Atcherley, Pavithra Pathirathna, et al. Analytical Chemistry 201789 ( (18), ), 9703–9711 . Copyright 2017 American Chemical Society.