Multi-Step Amperometry for Detecting Dopamine Using Boron-Doped Diamond Microelectrodes in the Striatum of the Mouse Brain

Abstract

The real-time measurement of dopamine concentration in the brain is crucial in elucidating dopamine-related physiological functions and pathologies and guiding therapeutic development. Boron-doped diamond (BDD) electrodes have emerged as promising tools for use in biological measurement because of their exceptional durabilities, sensitivities, and biocompatibilities, but electrochemically distinguishing dopamine from norepinephrine, which exhibits a similar chemical structure, remains challenging. Other substances that interfere with dopamine detection include tyrosine, L-3,4-dihydroxyphenylalanine, epinephrine, and serotonin. In this study, we developed a method of selectively detecting dopamine using a BDD microelectrode in vitro and then applied it to in vivo measurement in wild-type and dopamine-deficient mice. Methamphetamine, which is a dopamine-releasing agent, was used to assess the dopamine dynamics. In wild-type mice, methamphetamine induced a clear increase in the oxidation current, corresponding to dopamine release, whereas dopamine-deficient mice displayed no significant changes in current, despite methamphetamine also promoting norepinephrine release. Therefore, incorporating an oxidation potential of 0.2 V into multi-step amperometry enabled the highly sensitive and selective detection of dopamine in vivo using BDD microelectrodes. This technique provides a powerful approach for use in investigating brain function and dopamine-related pathophysiology.