Kwak, Youngjong

We report an innovative interleaved voltammetric strategy to simultaneously quantify tonic levels of dopamine and serotonin in vivo using a single unmodified microelectrode, advancing our capability to monitor complex neurochemical interactions.

ABSTRACT Real time, chronic electrochemical detection of neurotransmitters will provide a positive step in the treatment and understanding of neurological disease. However, current electrodes using carbon fibers (CF) fail to perform chronically. While diamond‐based coatings show promise in improving their longevity, achieving a uniform layer of such coatings on CFs is challenging, and the electrodes often lose sensitivity after coating. In this work, a complete and uniform boron‐doped nanocrystalline material grown in a diamond reactor (B‐NCD) was developed to coat CF microelectrodes for neurochemical sensing. The coating was characterized electrically, optically, mechanically, and chemically. The B‐NCD coated CF electrodes were able to detect phasic dopamine at a sensitivity comparable to the most widely used alternatives (uncoated and PEDOT:Nafion coated CFs). During biofouling testing, the B‐NCD coated CF electrodes demonstrated better stability than uncoated CFs and comparable performance to PEDOT:Nafion coated CFs. Moreover, B‐NCD exhibited no signs of degradation during consecutive FSCV applications, while uncoated and PEDOT:Nafion coated CF electrodes degraded significantly over time. Furthermore, the B‐NCD coating supported the survival and development of neurons and astrocytes in vitro, exhibited excellent adhesion and durability during mechanical bending testing, and enabled successful in vivo recording of phasic dopamine release in the rat brain. Overall, B‐NCD coated CFs present as an ideal candidate for chronic, flexible neural implantable electrodes for long‐term neurochemical monitoring.

Abstract Introduction: Opioid use disorder constitutes a significant health crisis in the United States, contributing to high rates of opioid overdose-related deaths. A major driver of these fatalities is fentanyl, a potent synthetic opioid with both sedative and analgesic properties. These properties that make fentanyl clinically effective also increase its addictive potential. Early in opioid addiction, abnormal increases in extracellular dopamine in the nucleus accumbens (NAc) reinforce excessive drug-seeking behaviors which can lead to fatal respiratory depression. Given this mechanism, we investigated whether high frequency stimulation (HFS), mimicking human deep brain stimulation (DBS) of the ventral tegmental area (VTA) could block NAc dopamine increase following an acute lethal dose of fentanyl. We hypothesized that VTA DBS would mitigate these dopaminergic responses and prevent fentanyl-induced respiratory failure. Methods: Multiple cyclic square wave voltammetry (M-CSWV), was applied via a carbon fiber microelectrode in the NAc of urethane-anesthetized male Sprague-Dawley rats. Dopamine levels were recorded at baseline and following acute fentanyl (30 µg/kg, i.v.). HFS (130 Hz frequency, 200 µsec pulse width, and 0.2 mA amplitude) was administered to the VTA before and during fentanyl exposure. Results: Acute fentanyl administration resulted in a 178.2% increase in NAc dopamine levels from baseline, accompanied by a decline in respiratory rates to critically low levels (45 breaths per minute vs. 102 bpm), eventually resulting in 100% mortality. HFS of the VTA did not significantly alter baseline tonic dopamine levels or prevent fentanyl-induced dopamine increase in the NAc but was able to fully rescue fentanyl-induced respiratory failure.

The distinct impacts of fouling mechanisms on a carbon fiber microelectrode and an Ag/AgCl reference electrode, affecting their performance in neurotransmitter detection via Fast-scan Cyclic Voltammetry.