Cocaine-Induced Changes in Tonic Dopamine Concentrations Measured Using Multiple-Cyclic Square Wave Voltammetry in vivo

Abstract

For over 40 years, in vivo microdialysis techniques have been at the forefront in measuring the effects of illicit substances on brain tonic extracellular levels of dopamine that underlie many aspects of drug addiction. However, the size of microdialysis probes and sampling rate may limit this technique’s ability to provide an accurate assessment of drug effects in microneural environments. A novel electrochemical method known as multiple-cyclic square wave voltammetry (M-CSWV), was recently developed to measure second-to-second changes in tonic dopamine levels at microelectrodes, providing spatiotemporal resolution superior to microdialysis. Here, we utilized M-CSWV and fast-scan cyclic voltammetry (FSCV) to measure changes in tonic or phasic dopamine release in the nucleus accumbens core (NAcc) after acute cocaine administration. Carbon-fiber microelectrodes (CFM) and stimulating electrodes were implanted into the NAcc and medial forebrain bundle (MFB) of urethane anesthetized (1.5 g/kg i.p.) Sprague-Dawley rats, respectively. Using FSCV, depths of each electrode were optimized by determining maximal MFB electrical stimulation-evoked phasic dopamine release. Changes in phasic responses were measured after a single dose of intravenous saline or cocaine hydrochloride (3 mg/kg; n = 4). In a separate group, changes in tonic dopamine levels were measured using M-CSWV after intravenous saline and after cocaine hydrochloride (3 mg/kg; n = 5). Both the phasic and tonic dopamine responses in the NAcc were augmented by the injection of cocaine compared to saline control. The phasic and tonic levels changed by approximately x2.4 and x1.9, respectively. These increases were largely consistent with previous studies using FSCV and microdialysis. However, the minimal disruption/disturbance of neuronal tissue by the CFM may explain why the baseline tonic dopamine values (134 ± 32 nM) measured by M-CSWV were found to be 10-fold higher when compared to conventional microdialysis. In this study, we demonstrated phasic dopamine dynamics in the NAcc with acute cocaine administration. M-CSWV was able to record rapid changes in tonic levels of dopamine, which cannot be achieved with other current voltammetric techniques. Taken together, M-CSWV has the potential to provide an unprecedented level of physiologic insight into dopamine signaling, both in vitro and in vivo, which will significantly enhance our understanding of neurochemical mechanisms underlying psychiatric conditions.

Accurate and stable chronic in vivo voltammetry enabled by a replaceable subcutaneous reference electrode

“…Therefore, there is no change in the ability of the carbon fiber working electrode to charge and discharge its electric double layer and oxidize and reduce electrochemical species when the reference electrode is placed outside of the brain. This technique can be applied to improve the reliability of potential control techniques for not only FSCV but also other electrochemical sensing studies ( Atcherley et al., 2013 ; He et al., 2020 ; Park et al., 2018 ; Taylor et al., 2017a ; Wassum et al., 2008 ; Yuen et al., 2021 ), voltage-controlled drug delivery ( Weaver et al., 2014 ), and voltage transient measurements in chronic stimulation studies ( Merrill et al., 2005 ; Zheng et al., 2020 , 2021 ).…”

“…This can complicate background subtraction and cause difficulty in identifying voltammograms as the analyte of interest. Other controlled potential electrochemical techniques for neurochemical sensing like multiple cyclic square wave voltammetry also frequently use brain-implanted Ag/AgCl wires as references and are likely affected by biofouling-induced polarization ( Yuen et al., 2021 ).…”

Determination of Drugs in Clinical Trials: Current Status and Outlook

“…Zheng et al prepared nano porous gold electrode and designed a DNA biosensor based on square wave voltammetry for the detection of lung resistance related protein gene [82]. In another clinical research study, dopamine concentration was measured using SWV, as illustrated in Figure 9 [83]. SWV exhibits much higher sensitivity than other voltametric methods due to the removal of the background current.…”

“…(D) Left-to-right: raw voltammogram following the removal of background currents, high-dimensional pseudo-color plot, M-CSWV signal calibration with tonic dopamine experiment (n = 4 electrodes). Reprinted by permission from [83].…”

Disrupted Decision-Making: EcoHIV Inoculation Following a History of Cocaine Use

“…Chronic use of the psychostimulant cocaine induces neurochemical and structural neuroadaptations in the frontal-striatal circuit. Motivationally relevant events, including acute cocaine use, induce activation of dopaminergic neurons in the VTA leading to a rapid potentiation of dopamine (DA) in the NAc (Bradberry et al, 1993; Pontieri et al, 1995; Yuen et al, 2021). Across repeated exposures to a motivationally relevant event (i.e., as would be observed with a history of cocaine use), however, dopamine function decreases in both the NAc (e.g., Volkow et al, 1990; Volkow et al, 1997; Ferris et al, 2012; Willuhn et al, 2014) and PFC (Briand et al, 2008); alterations in glutamate homeostasis also develop (for review, Kalivas, 2009).…”